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Selim title: Configurable Digital Virus Counter on Robust Universal DNA Chips date: 2020-10-22 journal: bioRxiv DOI: 10.1101/2020.10.22.350579 sha: doc_id: 102206 cord_uid: mb0qcd0b file: cache/cord-102199-mc6zruyx.json key: cord-102199-mc6zruyx authors: Toksvang, Linea Natalie; Schmidt, Magnus Strøh; Arup, Sofie; Larsen, Rikke Hebo; Frandsen, Thomas Leth; Schmiegelow, Kjeld; Rank, Cecilie Utke title: Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review date: 2019-01-30 journal: bioRxiv DOI: 10.1101/535518 sha: doc_id: 102199 cord_uid: mc6zruyx file: cache/cord-102189-wo9gg7nx.json key: cord-102189-wo9gg7nx authors: Mathew, Nimitha R.; Jayanthan, Jayalal K.; Smirnov, Ilya; Robinson, Jonathan L.; Axelsson, Hannes; Nakka, Sravya S.; Emmanouilidi, Aikaterini; Czarnewski, Paulo; Yewdell, William T.; Lebrero-Fernández, Cristina; Bernasconi, Valentina; Harandi, Ali M.; Lycke, Nils; Borcherding, Nicholas; Yewdell, Jonathan W.; Greiff, Victor; Bemark, Mats; Angeletti, Davide title: Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses date: 2020-08-24 journal: bioRxiv DOI: 10.1101/2020.08.24.264069 sha: doc_id: 102189 cord_uid: wo9gg7nx file: cache/cord-102279-ena1usqv.json key: cord-102279-ena1usqv authors: Long, Rory K. M.; Moriarty, Kathleen P.; Cardoen, Ben; Gao, Guang; Vogl, A. Wayne; Jean, François; Hamarneh, Ghassan; Nabi, Ivan R. title: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date: 2020-06-23 journal: bioRxiv DOI: 10.1101/2020.05.12.091611 sha: doc_id: 102279 cord_uid: ena1usqv file: cache/cord-102184-8u73adnk.json key: cord-102184-8u73adnk authors: Li, Jinzhi; Mahoney, Brennan Dale; Jacob, Miles Solomon; Caron, Sophie Jeanne Cécile title: Visual input into the Drosophila melanogaster mushroom body date: 2020-05-02 journal: bioRxiv DOI: 10.1101/2020.02.07.935924 sha: doc_id: 102184 cord_uid: 8u73adnk file: cache/cord-102231-cquxqbc2.json key: cord-102231-cquxqbc2 authors: Martinez, Xavier; Baaden, Marc title: FAIR sharing of molecular visualization experiences: from pictures in the cloud to collaborative virtual reality exploration in immersive 3D environments date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.08.27.270140 sha: doc_id: 102231 cord_uid: cquxqbc2 file: cache/cord-102350-e1vc2q4j.json key: cord-102350-e1vc2q4j authors: Yoon, Hye-Jin; Jeong, Hyunah; Lee, Hyung Ho; Jang, Soonmin title: Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation date: 2020-06-09 journal: bioRxiv DOI: 10.1101/2020.06.09.141630 sha: doc_id: 102350 cord_uid: e1vc2q4j file: cache/cord-102376-wk70iipl.json key: cord-102376-wk70iipl authors: Tausch, Simon H.; Loka, Tobias P.; Schulze, Jakob M.; Andrusch, Andreas; Klenner, Jeanette; Dabrowski, Piotr W.; Lindner, Martin S.; Nitsche, Andreas; Renard, Bernhard Y. title: PathoLive – Real-time pathogen identification from metagenomic Illumina datasets date: 2020-04-14 journal: bioRxiv DOI: 10.1101/402370 sha: doc_id: 102376 cord_uid: wk70iipl file: cache/cord-102226-aioqogaw.json key: cord-102226-aioqogaw authors: Chiu, Elliott S.; VandeWoude, Sue title: Presence of endogenous viral elements negatively correlates with FeLV susceptibility in puma and domestic cat cells date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.06.23.168351 sha: doc_id: 102226 cord_uid: aioqogaw file: cache/cord-102364-t5bt2eb4.json key: cord-102364-t5bt2eb4 authors: Yao, Dehui; Lao, Fang; Zhang, Zeyi; Liu, Yan; Cheng, Jianwei; Ding, Fengjiao; Wang, Xiaofei; Xi, Lun; Wang, Chuang; Yan, Xichong; Zhang, Rongkun; Ouyang, Fangxing; Ding, Hui; Ke, Tianyi title: Human H-ferritin presenting RBM of spike glycoprotein as potential vaccine of SARS-CoV-2 date: 2020-06-08 journal: bioRxiv DOI: 10.1101/2020.05.25.115618 sha: doc_id: 102364 cord_uid: t5bt2eb4 file: cache/cord-102151-26lumewy.json key: cord-102151-26lumewy authors: Cox, Robert M.; Sourimant, Julien; Govindarajan, Mugunthan; Natchus, Michael G.; Plemper, Richard K. title: Therapeutic Targeting of Measles Virus Polymerase with ERDRP-0519 Suppresses All RNA Synthesis Activity date: 2020-09-24 journal: bioRxiv DOI: 10.1101/2020.09.23.311043 sha: doc_id: 102151 cord_uid: 26lumewy file: cache/cord-102321-csdezu6y.json key: cord-102321-csdezu6y authors: Booeshaghi, A. Sina; Pachter, Lior title: Normalization of single-cell RNA-seq counts by log(x+1)* or log(1+x)* date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.05.19.100214 sha: doc_id: 102321 cord_uid: csdezu6y file: cache/cord-102336-ex3zlq38.json key: cord-102336-ex3zlq38 authors: De Wijngaert, Brent; Sultana, Shemaila; Dharia, Chhaya; Vanbuel, Hans; Shen, Jiayu; Vasilchuk, Daniel; Martinez, Sergio E.; Kandiah, Eaazhisai; Patel, Smita S.; Das, Kalyan title: Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.13.038620 sha: doc_id: 102336 cord_uid: ex3zlq38 file: cache/cord-102530-wetqqt2i.json key: cord-102530-wetqqt2i authors: Brandell, Ellen E.; Becker, Daniel J.; Sampson, Laura; Forbes, Kristian M. title: The rise of disease ecology date: 2020-07-17 journal: bioRxiv DOI: 10.1101/2020.07.16.207100 sha: doc_id: 102530 cord_uid: wetqqt2i file: cache/cord-102486-llmfgavd.json key: cord-102486-llmfgavd authors: Sprenger, Kayla G.; Louveau, Joy E.; Chakraborty, Arup K. title: Optimizing immunization protocols to elicit broadly neutralizing antibodies date: 2020-01-06 journal: bioRxiv DOI: 10.1101/2020.01.04.894857 sha: doc_id: 102486 cord_uid: llmfgavd file: cache/cord-102463-d440jsek.json key: cord-102463-d440jsek authors: Eguchi, Raphael R.; Anand, Namrata; Choe, Christian A.; Huang, Po-Ssu title: IG-VAE: Generative Modeling of Immunoglobulin Proteins by Direct 3D Coordinate Generation date: 2020-08-10 journal: bioRxiv DOI: 10.1101/2020.08.07.242347 sha: doc_id: 102463 cord_uid: d440jsek file: cache/cord-102270-rfhtlodc.json key: cord-102270-rfhtlodc authors: Azhar, Mohd.; Phutela, Rhythm; Ansari, Asgar Hussain; Sinha, Dipanjali; Sharma, Namrata; Kumar, Manoj; Aich, Meghali; Sharma, Saumya; Rauthan, Riya; Singhal, Khushboo; Lad, Harsha; Patra, Pradeep Kumar; Makharia, Govind; Chandak, Giriraj Ratan; Chakraborty, Debojyoti; Maiti, Souvik title: Rapid, field-deployable nucleobase detection and identification using FnCas9 date: 2020-04-21 journal: bioRxiv DOI: 10.1101/2020.04.07.028167 sha: doc_id: 102270 cord_uid: rfhtlodc file: cache/cord-102383-m5ahicqb.json key: cord-102383-m5ahicqb authors: Romano, Alessandra; Casazza, Marco; Gonella, Francesco title: Energy dynamics for systemic configurations of virus-host co-evolution date: 2020-05-15 journal: bioRxiv DOI: 10.1101/2020.05.13.092866 sha: doc_id: 102383 cord_uid: m5ahicqb file: cache/cord-102504-d840uu3e.json key: cord-102504-d840uu3e authors: Hass, Kenneth N.; Bao, Mengdi; He, Qian; Park, Myeongkee; Qin, Peiwu; Du, Ke title: Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing date: 2020-03-20 journal: bioRxiv DOI: 10.1101/2020.03.17.994137 sha: doc_id: 102504 cord_uid: d840uu3e file: cache/cord-102257-da4zn49x.json key: cord-102257-da4zn49x authors: Almodaresi, Fatemeh; Zakeri, Mohsen; Patro, Rob title: Puffaligner: An Efficient and Accurate Aligner Based on the Pufferfish Index date: 2020-08-12 journal: bioRxiv DOI: 10.1101/2020.08.11.246892 sha: doc_id: 102257 cord_uid: da4zn49x file: cache/cord-102324-tu804znm.json key: cord-102324-tu804znm authors: Le Sage, Valerie; Jones, Jennifer E.; 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Tchiengue, Barthelemy; van der Burgt, Xander title: Taxonomic revision of the threatened African genus Pseudohydrosme Engl. (Araceae), with P. ebo, a new, Critically Endangered species from Ebo, Cameroon date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.10.05.326850 sha: doc_id: 102366 cord_uid: 2alcsd1p file: cache/cord-102412-cnlvyey4.json key: cord-102412-cnlvyey4 authors: Tekman, Mehmet; Batut, Bérénice; Ostrovsky, Alexander; Antoniewski, Christophe; Clements, Dave; Ramirez, Fidel; Etherington, Graham J; Hotz, Hans-Rudolf; Scholtalbers, Jelle; Manning, Jonathan R; Bellenger, Lea; Doyle, Maria A; Heydarian, Mohammad; Huang, Ni; Soranzo, Nicola; Moreno, Pablo; Mautner, Stefan; Papatheodorou, Irene; Nekrutenko, Anton; Taylor, James; Blankenberg, Daniel; Backofen, Rolf; Grüning, Björn title: A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.06.06.137570 sha: doc_id: 102412 cord_uid: cnlvyey4 file: cache/cord-102612-xx5l8r9e.json key: cord-102612-xx5l8r9e authors: Kodani, Andrew; Knopp, Kristeene A.; Di Lullo, Elizabeth; Retallack, Hanna; Kriegstein, Arnold R.; DeRisi, Joseph L.; Reiter, Jeremy F. title: Zika virus alters centrosome organization to suppress the innate immune response date: 2020-09-15 journal: bioRxiv DOI: 10.1101/2020.09.15.298083 sha: doc_id: 102612 cord_uid: xx5l8r9e file: cache/cord-102356-knvfbuzv.json key: cord-102356-knvfbuzv authors: Knyazev, Sergey; Tsyvina, Viachaslau; Shankar, Anupama; Melnyk, Andrew; Artyomenko, Alexander; Malygina, Tatiana; Porozov, Yuri B.; Campbell, Ellsworth M.; Mangul, Serghei; Switzer, William M.; Skums, Pavel; Zelikovsky, Alex title: Accurate assembly of minority viral haplotypes from next-generation sequencing through efficient noise reduction date: 2020-10-08 journal: bioRxiv DOI: 10.1101/264242 sha: doc_id: 102356 cord_uid: knvfbuzv file: cache/cord-102377-n57hoty4.json key: cord-102377-n57hoty4 authors: Egli, Adrian; Goldman, Nina; Müller, Nicola F.; Brunner, Myrta; Wüthrich, Daniel; Tschudin-Sutter, Sarah; Hodcroft, Emma; Neher, Richard; Saalfrank, Claudia; Hadfield, James; Bedford, Trevor; Syedbasha, Mohammedyaseen; Vogel, Thomas; Augustin, Noémie; Bauer, Jan; Sailer, Nadine; Amar-Sliwa, Nadezhda; Lang, Daniela; Seth-Smith, Helena M.B.; Blaich, Annette; Hollenstein, Yvonne; Dubuis, Olivier; Nägele, Michael; Buser, Andreas; Nickel, Christian H.; Ritz, Nicole; Zeller, Andreas; Stadler, Tanja; Battegay, Manuel; Schneider-Sliwa, Rita title: High-resolution influenza mapping of a city reveals socioeconomic determinants of transmission within and between urban quarters date: 2020-04-04 journal: bioRxiv DOI: 10.1101/2020.04.03.023135 sha: doc_id: 102377 cord_uid: n57hoty4 file: cache/cord-102367-l1u094bp.json key: cord-102367-l1u094bp authors: López, María S.; Jordan, Daniela I.; Blatter, Evelyn; Walker, Elisabet; Gómez, Andrea A.; Müller, Gabriela V.; Mendicino, Diego; Estallo, Elizabet L. title: Dengue arbovirus affecting temperate Argentina province for more than a decade 2009-2020 date: 2020-08-11 journal: bioRxiv DOI: 10.1101/2020.08.11.246272 sha: doc_id: 102367 cord_uid: l1u094bp file: cache/cord-102555-vnmc9ii8.json key: cord-102555-vnmc9ii8 authors: Araki, Takuma; Tanatani, Kenta; Kamimura, Naofumi; Otsuka, Yuichiro; Yamaguchi, Muneyoshi; Nakamura, Masaya; Masai, Eiji title: Sphingobium sp. 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J.; He, Xiaotong; O’Sullivan, James; Ollier, William E.R.; Chinoy, Hector; Pendleton, Neil; Payton, Antony; Hampson, Lynne; Hampson, Ian; Lamb, Janine A. title: Microbial and autoantibody immunogenic repertoires in TIF1γ autoantibody positive dermatomyositis date: 2020-03-26 journal: bioRxiv DOI: 10.1101/2020.03.25.007534 sha: doc_id: 102502 cord_uid: hroxg2u1 file: cache/cord-102551-8igfuaw2.json key: cord-102551-8igfuaw2 authors: Boonyaratanakornkit, Jim; Singh, Suruchi; Weidle, Connor; Rodarte, Justas; Bakthavatsalam, Ramasamy; Perkins, Jonathan; Stewart-Jones, Guillaume B.E.; Kwong, Peter D.; McGuire, Andrew T.; Pancera, Marie; Taylor, Justin J. title: Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection date: 2020-10-30 journal: bioRxiv DOI: 10.1101/2020.06.15.153478 sha: doc_id: 102551 cord_uid: 8igfuaw2 file: cache/cord-102705-mcit0luk.json key: cord-102705-mcit0luk authors: Gupta, Chitrak; Cava, John Kevin; Sarkar, Daipayan; Wilson, Eric; Vant, John; Murray, Steven; Singharoy, Abhishek; Karmaker, Shubhra Kanti title: Mind reading of the proteins: Deep-learning to forecast molecular dynamics date: 2020-07-29 journal: bioRxiv DOI: 10.1101/2020.07.28.225490 sha: doc_id: 102705 cord_uid: mcit0luk file: cache/cord-102729-b1q7gbd6.json key: cord-102729-b1q7gbd6 authors: Mickael, Alexandra; Klimovich, Pavel; Henckel, Patrick; Kubick, Norwin; Mickael, Michel E title: Asip (Agouti-signaling protein) aggression gene regulate auditory processing genes in mice date: 2020-06-12 journal: bioRxiv DOI: 10.1101/2020.06.10.141325 sha: doc_id: 102729 cord_uid: b1q7gbd6 file: cache/cord-102720-ka95resa.json key: cord-102720-ka95resa authors: Aguilar, César; Verdel-Aranda, Karina; Ramos-Aboites, Hilda E.; Morales, Marco Antonio; Licona-Cassani, Cuauhtémoc; Barona-Gómez, Francisco title: Convergent evolution of Streptomyces protease inhibitors involving a tRNA-mediated condensation-minus NRPS date: 2020-10-27 journal: bioRxiv DOI: 10.1101/2020.10.26.356543 sha: doc_id: 102720 cord_uid: ka95resa file: cache/cord-102823-zult69f2.json key: cord-102823-zult69f2 authors: Nguyen, Thin; Le, Hang; Quinn, Thomas P.; Nguyen, Tri; Le, Thuc Duy; Venkatesh, Svetha title: GraphDTA: Predicting drug–target binding affinity with graph neural networks date: 2020-10-02 journal: bioRxiv DOI: 10.1101/684662 sha: doc_id: 102823 cord_uid: zult69f2 file: cache/cord-102444-n4vdxdhp.json key: cord-102444-n4vdxdhp authors: Rhea, Elizabeth M.; Logsdon, Aric F.; Hansen, Kim M.; Williams, Lindsey; Reed, May; Baumann, Kristen; Holden, Sarah; Raber, Jacob; Banks, William A.; Erickson, Michelle A. title: The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation date: 2020-07-15 journal: bioRxiv DOI: 10.1101/2020.07.15.205229 sha: doc_id: 102444 cord_uid: n4vdxdhp file: cache/cord-102511-7zgd45fl.json key: cord-102511-7zgd45fl authors: Khodakov, Dmitriy; Li, Jiaming; Zhang, Jinny X.; Zhang, David Yu title: Donut PCR: a rapid, portable, multiplexed, and quantitative DNA detection platform with single-nucleotide specificity date: 2020-05-05 journal: bioRxiv DOI: 10.1101/2020.04.24.058453 sha: doc_id: 102511 cord_uid: 7zgd45fl file: cache/cord-102481-obig3mu1.json key: cord-102481-obig3mu1 authors: Alić, Ivan; Goh, Pollyanna A; Murray, Aoife; Portelius, Erik; Gkanatsiou, Eleni; Gough, Gillian; Mok, Kin Y; Koschut, David; Brunmeir, Reinhard; Yeap, Yee Jie; O’Brien, Niamh L; Groet, Jurgen; Shao, Xiaowei; Havlicek, Steven; Dunn, N Ray; Kvartsberg, Hlin; Brinkmalm, Gunnar; Hithersay, Rosalyn; Startin, Carla; Hamburg, Sarah; Phillips, Margaret; Pervushin, Konstantin; Turmaine, Mark; Wallon, David; Rovelet-Lecrux, Anne; Soininen, Hilkka; Volpi, Emanuela; Martin, Joanne E; Foo, Jia Nee; Becker, David L; Rostagno, Agueda; Ghiso, Jorge; Krsnik, Željka; Šimić, Goran; Kostović, Ivica; Mitrečić, Dinko; Francis, Paul T; Blennow, Kaj; Strydom, Andre; Hardy, John; Zetterberg, Henrik; Nižetić, Dean title: “Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain” date: 2020-01-31 journal: bioRxiv DOI: 10.1101/2020.01.29.918037 sha: doc_id: 102481 cord_uid: obig3mu1 file: cache/cord-102613-hly07ne3.json key: cord-102613-hly07ne3 authors: Danko, David; Bezdan, Daniela; Afshinnekoo, Ebrahim; Ahsanuddin, Sofia; Bhattacharya, Chandrima; Butler, Daniel J; Chng, Kern Rei; Donnellan, Daisy; Hecht, Jochen; Kuchin, Katerina; Karasikov, Mikhail; Lyons, Abigail; Mak, Lauren; Meleshko, Dmitry; Mustafa, Harun; Mutai, Beth; Neches, Russell Y; Ng, Amanda; Nikolayeva, Olga; Nikolayeva, Tatyana; Png, Eileen; Ryon, Krista; Sanchez, Jorge L; Shaaban, Heba; Sierra, Maria A; Thomas, Dominique; Young, Ben; Abudayyeh, Omar O.; Alicea, Josue; Bhattacharyya, Malay; Blekhman, Ran; Castro-Nallar, Eduardo; Cañas, Ana M; Chatziefthimiou, Aspassia D; Crawford, Robert W; De Filippis, Francesca; Deng, Youping; Desnues, Christelle; Dias-Neto, Emmanuel; Dybwad, Marius; Elhaik, Eran; Ercolini, Danilo; Frolova, Alina; Gankin, Dennis; Gootenberg, Jonathan S.; Graf, Alexandra B; Green, David C; Hajirasouliha, Iman; Hernandez, Mark; Iraola, Gregorio; Jang, Soojin; Kahles, Andre; Kelly, Frank J; Knights, Kaymisha; Kyrpides, Nikos C; Łabaj, Paweł P; Lee, Patrick K H; Leung, Marcus H Y; Ljungdahl, Per; Mason-Buck, Gabriella; McGrath, Ken; Meydan, Cem; Mongodin, Emmanuel F; Moraes, Milton Ozorio; Nagarajan, Niranjan; Nieto-Caballero, Marina; Noushmehr, Houtan; Oliveira, Manuela; Ossowski, Stephan; Osuolale, Olayinka O; Özcan, Orhan; Paez-Espino, David; Rascovan, Nicolas; Richard, Hugues; Rätsch, Gunnar; Schriml, Lynn M; Semmler, Torsten; Sezerman, Osman U; Shi, Leming; Shi, Tieliu; Song, Le Huu; Suzuki, Haruo; Tighe, Scott W; Tong, Xinzhao; Udekwu, Klas I; Ugalde, Juan A; Valentine, Brandon; Vassilev, Dimitar I; Vayndorf, Elena; Velavan, Thirumalaisamy P; Wu, Jun; Zambrano, María M; Zhu, Jifeng; Zhu, Sibo; Mason, Christopher E title: Global Genetic Cartography of Urban Metagenomes and Anti-Microbial Resistance date: 2020-05-04 journal: bioRxiv DOI: 10.1101/724526 sha: doc_id: 102613 cord_uid: hly07ne3 file: cache/cord-102634-0n42h72w.json key: cord-102634-0n42h72w authors: Willforss, Jakob; Siino, Valentina; Levander, Fredrik title: OmicLoupe: Facilitating biological discovery by interactive exploration of multiple omic datasets and statistical comparisons date: 2020-10-22 journal: bioRxiv DOI: 10.1101/2020.10.22.349944 sha: doc_id: 102634 cord_uid: 0n42h72w file: cache/cord-102661-lh7992rl.json key: cord-102661-lh7992rl authors: Valentine, Charles C.; Young, Robert R.; Fielden, Mark R.; Kulkarni, Rohan; Williams, Lindsey N.; Li, Tan; Minocherhomji, Sheroy; Salk, Jesse J. title: Direct Quantification of in vivo Mutagenesis and Carcinogenesis Using Duplex Sequencing date: 2020-11-03 journal: bioRxiv DOI: 10.1101/2020.06.28.176685 sha: doc_id: 102661 cord_uid: lh7992rl file: cache/cord-102808-c7ajfvt5.json key: cord-102808-c7ajfvt5 authors: Sundqvist, Martina; Holdfeldt, André; Wright, Shane C.; Møller, Thor C.; Siaw, Esther; Jennbacken, Karin; Franzyk, Henrik; Bouvier, Michel; Dahlgren, Claes; Forsman, Huamei title: Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.04.30.070011 sha: doc_id: 102808 cord_uid: c7ajfvt5 file: cache/cord-102608-1ilforzm.json key: cord-102608-1ilforzm authors: Litviňuková, Monika; Talavera-López, Carlos; Maatz, Henrike; Reichart, Daniel; Worth, Catherine L.; Lindberg, Eric L.; Kanda, Masatoshi; Polanski, Krzysztof; Fasouli, Eirini S.; Samari, Sara; Roberts, Kenny; Tuck, Liz; Heinig, Matthias; DeLaughter, Daniel M.; McDonough, Barbara; Wakimoto, Hiroko; Gorham, Joshua M.; Nadelmann, Emily R.; Mahbubani, Krishnaa T.; Saeb-Parsy, Kourosh; Patone, Giannino; Boyle, Joseph J.; Zhang, Hongbo; Zhang, Hao; Viveiros, Anissa; Oudit, Gavin Y.; Bayraktar, Omer; Seidman, J. G.; Seidman, Christine; Noseda, Michela; Hübner, Norbert; Teichmann, Sarah A. title: Cells and gene expression programs in the adult human heart date: 2020-04-10 journal: bioRxiv DOI: 10.1101/2020.04.03.024075 sha: doc_id: 102608 cord_uid: 1ilforzm file: cache/cord-102704-wfuzk2dp.json key: cord-102704-wfuzk2dp authors: Meza, Diana K.; Broos, Alice; Becker, Daniel J.; Behdenna, Abdelkader; Willett, Brian J.; Viana, Mafalda; Streicker, Daniel G. title: Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities date: 2020-04-30 journal: bioRxiv DOI: 10.1101/2020.04.24.060095 sha: doc_id: 102704 cord_uid: wfuzk2dp file: cache/cord-102454-fqwks0rb.json key: cord-102454-fqwks0rb authors: Liao, Yan Shin J.; Kuan, Shin Ping; Guevara, Maria V.; Collins, Emily N.; Atanasova, Kalina R.; Dadural, Joshua S.; Vogt, Kevin; Schurmann, Veronica; Reznikov, Leah R. title: Acid exposure impairs mucus secretion and disrupts mucus transport in neonatal piglet airways date: 2019-06-13 journal: bioRxiv DOI: 10.1101/669879 sha: doc_id: 102454 cord_uid: fqwks0rb file: cache/cord-102770-t4zgph9k.json key: cord-102770-t4zgph9k authors: McComb, Scott; Nguyen, Tina; Henry, Kevin A.; Bloemberg, Darin; Maclean, Susanne; Gilbert, Rénald; Gadoury, Christine; Pon, Rob; Sulea, Traian; Zhu, Qin; Weeratna, Risini D. title: Fine Molecular Tuning of Chimeric Antigen Receptors through Hinge Length Optimization date: 2020-10-30 journal: bioRxiv DOI: 10.1101/2020.10.30.360925 sha: doc_id: 102770 cord_uid: t4zgph9k file: cache/cord-102809-06izdji8.json key: cord-102809-06izdji8 authors: Siddiqui, Nabil A.; Houson, Hailey A.; Thomas, Shindu C.; Blanco, Jose R.; O’Donnell, Robert E.; Hassett, Daniel J.; Lapi, Suzanne E.; Kotagiri, Nalinikanth title: Radiolabelled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesicles in vivo date: 2020-08-06 journal: bioRxiv DOI: 10.1101/2020.08.06.240119 sha: doc_id: 102809 cord_uid: 06izdji8 file: cache/cord-102842-51n5mnjb.json key: cord-102842-51n5mnjb authors: Węglarz-Tomczak, Ewelina; Tomczak, Jakub M.; Talma, Michał; Brul, Stanley title: Ebselen as a highly active inhibitor of PLProCoV2 date: 2020-05-17 journal: bioRxiv DOI: 10.1101/2020.05.17.100768 sha: doc_id: 102842 cord_uid: 51n5mnjb file: cache/cord-102891-0z397ppn.json key: cord-102891-0z397ppn authors: Wren, Brandi; Ray, Ian S.; Remis, Melissa; Gillespie, Thomas R.; Camp, Joseph title: Social contact behaviors are associated with infection status for whipworm (Trichuris sp.) in wild vervet monkeys (Chlorocebus pygerythrus) date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.10.07.329409 sha: doc_id: 102891 cord_uid: 0z397ppn file: cache/cord-102778-b1ul7zug.json key: cord-102778-b1ul7zug authors: Serrao, Juliet.M.; Goodchild, Colin.S. title: Alfaxalone activates Human Pregnane-X Receptors with greater efficacy than Allopregnanolone: an in-vitro study with implications for neuroprotection during anesthesia date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.05.284075 sha: doc_id: 102778 cord_uid: b1ul7zug file: cache/cord-102976-cic1gxrk.json key: cord-102976-cic1gxrk authors: Patel, Roosheel S.; Tomlinson, Joy E.; Divers, Thomas J.; Van de Walle, Gerlinde R.; Rosenberg, Brad R. title: Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells date: 2020-05-07 journal: bioRxiv DOI: 10.1101/2020.05.05.077362 sha: doc_id: 102976 cord_uid: cic1gxrk file: cache/cord-102734-ltuqoa2b.json key: cord-102734-ltuqoa2b authors: Tsai, Hsiang-Yu; Rubenstein, Dustin R.; Chen, Bo-Fei; Liu, Mark; Chan, Shih-Fan; Chen, De-Pei; Sun, Syuan-Jyun; Yuan, Tzu-Neng; Shen, Sheng-Feng title: Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance date: 2020-05-04 journal: bioRxiv DOI: 10.1101/2020.05.03.075325 sha: doc_id: 102734 cord_uid: ltuqoa2b file: cache/cord-102868-wnsgjdcp.json key: cord-102868-wnsgjdcp authors: Love, R. Rebecca; Pombi, Marco; Guelbeogo, Moussa W.; Campbell, Nathan R.; Stephens, Melissa T.; Dabire, Roch K.; Costantini, Carlo; della Torre, Alessandra; Besansky, Nora J. title: Inversion Genotyping in the Anopheles gambiae Complex Using High-Throughput Array and Sequencing Platforms date: 2020-05-28 journal: bioRxiv DOI: 10.1101/2020.05.25.114793 sha: doc_id: 102868 cord_uid: wnsgjdcp file: cache/cord-102898-eyyd7ent.json key: cord-102898-eyyd7ent authors: Rizvi, Vaseef A.; Sarkar, Maharnob; Roy, Rahul title: Translation regulation of Japanese encephalitis virus revealed by ribosome profiling date: 2020-07-17 journal: bioRxiv DOI: 10.1101/2020.07.16.206920 sha: doc_id: 102898 cord_uid: eyyd7ent file: cache/cord-102766-n6mpdhyu.json key: cord-102766-n6mpdhyu authors: Alam, Md. Nafis Ul; Chowdhury, Umar Faruq title: Short k-mer Abundance Profiles Yield Robust Machine Learning Features and Accurate Classifiers for RNA Viruses date: 2020-06-25 journal: bioRxiv DOI: 10.1101/2020.06.25.170779 sha: doc_id: 102766 cord_uid: n6mpdhyu file: cache/cord-102632-yazl9usb.json key: cord-102632-yazl9usb authors: Lobet, Guillaume; Descamps, Charlotte; Leveau, Lola; Guillet, Alain; Rees, Jean-François title: QuoVidi: a open-source web application for the organisation of large scale biological treasure hunts date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.06.30.177006 sha: doc_id: 102632 cord_uid: yazl9usb file: cache/cord-102866-40s64455.json key: cord-102866-40s64455 authors: Bhadra, Sanchita; Maranhao, Andre C.; Ellington, Andrew D. title: One enzyme reverse transcription qPCR using Taq DNA polymerase date: 2020-05-30 journal: bioRxiv DOI: 10.1101/2020.05.27.120238 sha: doc_id: 102866 cord_uid: 40s64455 file: cache/cord-102668-1yc38ok1.json key: cord-102668-1yc38ok1 authors: Siddiqui, Shoib S.; Dhar, Chirag; Sundaramurthy, Venkatasubramaniam; Sasmal, Aniruddha; Yu, Hai; Bandala-Sanchez, Esther; Li, Miaomiao; Zhang, Xiaoxiao; Chen, Xi; Harrison, Leonard C.; Xu, Ding; Varki, Ajit title: Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition date: 2020-07-15 journal: bioRxiv DOI: 10.1101/2020.07.15.198010 sha: doc_id: 102668 cord_uid: 1yc38ok1 file: cache/cord-102968-mhawyect.json key: cord-102968-mhawyect authors: Desirò, Daniel; Hölzer, Martin; Ibrahim, Bashar; Marz, Manja title: SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structural RNAs date: 2018-09-23 journal: bioRxiv DOI: 10.1101/424002 sha: doc_id: 102968 cord_uid: mhawyect file: cache/cord-102763-tc1z0nm9.json key: cord-102763-tc1z0nm9 authors: Zhang, Yuan; Wei, Yanqiu; Li, Yunlong; Wang, Xuan; Liu, Yang; Tian, Deyu; Jia, Xiaojuan; Gong, Rui; Liu, Wenjun; Yang, Limin title: IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability date: 2020-05-21 journal: bioRxiv DOI: 10.1101/2020.05.21.108159 sha: doc_id: 102763 cord_uid: tc1z0nm9 file: cache/cord-102918-bkyk7or9.json key: cord-102918-bkyk7or9 authors: Burns, C. Sean; Nix, Tyler; Shapiro, Robert M.; Huber, Jeffrey T. title: Methodological Issues with Search in MEDLINE: A Longitudinal Query Analysis date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.22.110403 sha: doc_id: 102918 cord_uid: bkyk7or9 file: cache/cord-102749-tgka0pl0.json key: cord-102749-tgka0pl0 authors: Tovo, Anna; Menzel, Peter; Krogh, Anders; Lagomarsino, Marco Cosentino; Suweis, Samir title: Taxonomic classification method for metagenomics based on core protein families with Core-Kaiju date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.01.08.898395 sha: doc_id: 102749 cord_uid: tgka0pl0 file: cache/cord-102892-nt1zoktv.json key: cord-102892-nt1zoktv authors: Sweeney, Blake A.; Hoksza, David; Nawrocki, Eric P.; Ribas, Carlos Eduardo; Madeira, Fábio; Cannone, Jamie J.; Gutell, Robin; Maddala, Aparna; Meade, Caeden; Williams, Loren Dean; Petrov, Anton S.; Chan, Patricia P.; Lowe, Todd M.; Finn, Robert D.; Petrov, Anton I. title: R2DT: computational framework for template-based RNA secondary structure visualisation across non-coding RNA types date: 2020-09-11 journal: bioRxiv DOI: 10.1101/2020.09.10.290924 sha: doc_id: 102892 cord_uid: nt1zoktv file: cache/cord-102905-rlee32x7.json key: cord-102905-rlee32x7 authors: Leis, Jonathan; Luan, Chi-Hao; Audia, James E.; Dunne, Sara F.; Heath, Carissa M. title: Ilaprazole and other novel prazole-based compounds that bind Tsg101 inhibit viral budding of HSV-1/2 and HIV from cells date: 2020-05-04 journal: bioRxiv DOI: 10.1101/2020.05.04.075036 sha: doc_id: 102905 cord_uid: rlee32x7 file: cache/cord-103015-3dxwbmd2.json key: cord-103015-3dxwbmd2 authors: Shengjuler, Djoshkun; Chan, Yan Mei; Sun, Simou; Moustafa, Ibrahim M.; Li, Zhen-Lu; Gohara, David W.; Buck, Matthias; Cremer, Paul S.; Boehr, David D.; Cameron, Craig E. title: The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain date: 2017-08-04 journal: bioRxiv DOI: 10.1101/172742 sha: doc_id: 103015 cord_uid: 3dxwbmd2 file: cache/cord-102920-z5q3wo7v.json key: cord-102920-z5q3wo7v authors: Sang, Eric R.; Tian, Yun; Gong, Yuanying; Miller, Laura C.; Sang, Yongming title: Integrate Structural Analysis, Isoform Diversity, and Interferon-Inductive Propensity of ACE2 to Refine SARS-CoV2 Susceptibility Prediction in Vertebrates date: 2020-06-28 journal: bioRxiv DOI: 10.1101/2020.06.27.174961 sha: doc_id: 102920 cord_uid: z5q3wo7v file: cache/cord-102908-sr7j8z9c.json key: cord-102908-sr7j8z9c authors: Mersmann, Sophia F.; Johns, Emma; Yong, Tracer; McEwan, Will A.; James, Leo C.; Cohen, Edward A.K.; Grove, Joe title: Learning to count: determining the stoichiometry of bio-molecular complexes using fluorescence microscopy and statistical modelling date: 2020-07-24 journal: bioRxiv DOI: 10.1101/2020.07.23.217745 sha: doc_id: 102908 cord_uid: sr7j8z9c file: cache/cord-102967-dx0tg077.json key: cord-102967-dx0tg077 authors: Mahajan, Lakshmi S.; Kim, Grace Eunyoo; Kwak, Hojoong title: Mapping RNA dependent RNA polymerase activity and immune gene expression using PRO-seq date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.15.151738 sha: doc_id: 102967 cord_uid: dx0tg077 file: cache/cord-102958-q8jamg07.json key: cord-102958-q8jamg07 authors: Hahka, Taija M.; Xia, Zhiqiu; Hong, Juan; Kitzerow, Oliver; Nahama, Alexis; Zucker, Irving H.; Wang, Hanjun title: Resiniferatoxin (RTX) ameliorates acute respiratory distress syndrome (ARDS) in a rodent model of lung injury date: 2020-09-14 journal: bioRxiv DOI: 10.1101/2020.09.14.296731 sha: doc_id: 102958 cord_uid: q8jamg07 file: cache/cord-102886-oo7q05ml.json key: cord-102886-oo7q05ml authors: Gomes, Fabio M.; Tyner, Miles D.W.; Barletta, Ana Beatriz F.; Yenkoidiok-Douti, Lampougin; Canepa, Gaspar E.; Molina-Cruz, Alvaro; Barillas-Mury, Carolina title: “Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes” date: 2020-09-10 journal: bioRxiv DOI: 10.1101/2020.09.09.290312 sha: doc_id: 102886 cord_uid: oo7q05ml file: cache/cord-102916-t2lcd300.json key: cord-102916-t2lcd300 authors: Cai, Guoshuai; Xiao, Feifei title: SCANNER: A Web Resource for Annotation, Visualization and Sharing of Single Cell RNA-seq Data date: 2020-07-14 journal: bioRxiv DOI: 10.1101/2020.01.25.919712 sha: doc_id: 102916 cord_uid: t2lcd300 file: cache/cord-102811-jlr4vb4u.json key: cord-102811-jlr4vb4u authors: Baumeister, Sebastian E; Karch, André; Bahls, Martin; Teumer, Alexander; Leitzmann, Michael F; Baurecht, Hansjörg title: Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study date: 2019-10-29 journal: bioRxiv DOI: 10.1101/819821 sha: doc_id: 102811 cord_uid: jlr4vb4u file: cache/cord-102977-yci9kq6x.json key: cord-102977-yci9kq6x authors: Liu, Haiming; Luo, Jiaohua; Guillory, Bobby; Chen, Ji-an; Zang, Pu; Yoeli, Jordan K.; Hernandez, Yamileth; Lee, Ian (In-gi); Anderson, Barbara; Storie, Mackenzie; Tewnion, Alison; Garcia, Jose M. title: GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia date: 2019-12-06 journal: bioRxiv DOI: 10.1101/866376 sha: doc_id: 102977 cord_uid: yci9kq6x file: cache/cord-102835-71ome9h8.json key: cord-102835-71ome9h8 authors: Levinson, Maxwell Adam; Niestroy, Justin; Manir, Sadnan Al; Fairchild, Karen; Lake, Douglas E.; Moorman, J. Randall; Clark, Timothy title: FAIRSCAPE: A Framework for FAIR and Reproducible Biomedical Analytics date: 2020-08-15 journal: bioRxiv DOI: 10.1101/2020.08.10.244947 sha: doc_id: 102835 cord_uid: 71ome9h8 file: cache/cord-102931-vxkbctiz.json key: cord-102931-vxkbctiz authors: Mao, Kai; Breen, Peter; Ruvkun, Gary title: Induction of RNA interference by C. elegans mitochondrial dysfunction via the DRH-1/RIG-I homologue RNA helicase and the EOL-1/RNA decapping enzyme date: 2020-06-06 journal: bioRxiv DOI: 10.1101/2020.06.05.136978 sha: doc_id: 102931 cord_uid: vxkbctiz file: cache/cord-102935-cx3elpb8.json key: cord-102935-cx3elpb8 authors: Hassani-Pak, Keywan; Singh, Ajit; Brandizi, Marco; Hearnshaw, Joseph; Amberkar, Sandeep; Phillips, Andrew L.; Doonan, John H.; Rawlings, Chris title: KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species date: 2020-04-24 journal: bioRxiv DOI: 10.1101/2020.04.02.017004 sha: doc_id: 102935 cord_uid: cx3elpb8 file: cache/cord-102570-lpwwlrqm.json key: cord-102570-lpwwlrqm authors: Fenn, Gareth D.; Waller-Evans, Helen; Atack, John R.; Bax, Benjamin D. title: Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase) date: 2020-08-18 journal: bioRxiv DOI: 10.1101/2020.07.08.193284 sha: doc_id: 102570 cord_uid: lpwwlrqm file: cache/cord-102964-zh737cjk.json key: cord-102964-zh737cjk authors: Ferraro, Francesco; Costa, Joana R.; Ketteler, Robin; Kriston-Vizi, Janos; Cutler, Daniel F. title: Modulation of endothelial organelle size as an antithrombotic strategy date: 2020-05-17 journal: bioRxiv DOI: 10.1101/2020.05.16.099580 sha: doc_id: 102964 cord_uid: zh737cjk file: cache/cord-103077-sh4w2mye.json key: cord-103077-sh4w2mye authors: Lu, Shuai; Li, Yuguang; Wang, Fei; Nan, Xiaofei; Zhang, Shoutao title: Leveraging Sequential and Spatial Neighbors Information by Using CNNs Linked With GCNs for Paratope Prediction date: 2020-10-16 journal: bioRxiv DOI: 10.1101/2020.10.15.339168 sha: doc_id: 103077 cord_uid: sh4w2mye file: cache/cord-103135-nly9vojr.json key: cord-103135-nly9vojr authors: Fletcher, Nicola F.; Meredith, Luke W.; Tidswell, Emma; Bryden, Steven R; Gonçalves-Carneiro, Daniel; Chaudhry, Yasmin; Lowe, Claire Shannon; Folan, Michael A.; Lefteri, Daniella A; Pingen, Marieke; Bailey, Dalan; McKimmie, Clive S.; Baird, Alan W. title: A novel antiviral formulation inhibits a range of enveloped viruses date: 2020-03-30 journal: bioRxiv DOI: 10.1101/2020.03.29.009464 sha: doc_id: 103135 cord_uid: nly9vojr file: cache/cord-103071-6cgih8o9.json key: cord-103071-6cgih8o9 authors: Mead, Benjamin E.; Hattori, Kazuki; Levy, Lauren; Vukovic, Marko; Sze, Daphne; Matute, Juan D.; Duan, Jinzhi; Langer, Robert; Blumberg, Richard S.; Ordovas-Montanes, Jose; Shalek, Alex K.; Karp, Jeffrey M. title: High-throughput organoid screening enables engineering of intestinal epithelial composition date: 2020-04-28 journal: bioRxiv DOI: 10.1101/2020.04.27.063727 sha: doc_id: 103071 cord_uid: 6cgih8o9 file: cache/cord-103055-071a5b0x.json key: cord-103055-071a5b0x authors: Rathbun, LI; Aljiboury, AA; Bai, X; Manikas, J; Amack, JD; Bembenek, JN; Hehnly, H title: PLK1- and PLK4-mediated asymmetric mitotic centrosome size and positioning in the early zebrafish embryo date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.13.039362 sha: doc_id: 103055 cord_uid: 071a5b0x file: cache/cord-103081-k7ev5qkn.json key: cord-103081-k7ev5qkn authors: Janosevic, Danielle; Myslinski, Jered; McCarthy, Thomas; Zollman, Amy; Syed, Farooq; Xuei, Xiaoling; Gao, Hongyu; Liu, Yunlong; Collins, Kimberly S.; Cheng, Ying-Hua; Winfree, Seth; El-Achkar, Tarek M.; Maier, Bernhard; Ferreira, Ricardo Melo; Eadon, Michael T.; Hato, Takashi; Dagher, Pierre C. title: The orchestrated cellular and molecular responses of the kidney to endotoxin define the sepsis timeline date: 2020-05-30 journal: bioRxiv DOI: 10.1101/2020.05.27.118620 sha: doc_id: 103081 cord_uid: k7ev5qkn file: cache/cord-103085-vf4qyvft.json key: cord-103085-vf4qyvft authors: Seitz, Christian; Casalino, Lorenzo; Konecny, Robert; Huber, Gary; Amaro, Rommie E.; McCammon, J. Andrew title: Multiscale simulations examining glycan shield effects on drug binding to influenza neuraminidase date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.08.12.248690 sha: doc_id: 103085 cord_uid: vf4qyvft file: cache/cord-103105-iqjksoim.json key: cord-103105-iqjksoim authors: Marinaik, Chandranaik B.; Kingstad-Bakke, Brock; Lee, Woojong; Hatta, Masato; Sonsalla, Michelle; Larsen, Autumn; Neldner, Brandon; Gasper, David J.; Kedl, Ross M.; Kawaoka, Yoshihiro; Suresh, M. title: Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants date: 2020-07-10 journal: bioRxiv DOI: 10.1101/2020.07.10.197459 sha: doc_id: 103105 cord_uid: iqjksoim file: cache/cord-103046-w8bm4p44.json key: cord-103046-w8bm4p44 authors: Suarez, David L.; Pantin-Jackwood, Mary J.; Swayne, David E.; Lee, Scott A.; DeBlois, Suzanne M.; Spackman, Erica title: Lack of susceptibility of poultry to SARS-CoV-2 and MERS-CoV date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.16.154658 sha: doc_id: 103046 cord_uid: w8bm4p44 file: cache/cord-103041-ymr3e60k.json key: cord-103041-ymr3e60k authors: Wu, Yue; Hengen, Keith B.; Turrigiano, Gina G.; Gjorgjieva, Julijana title: Homeostatic mechanisms regulate distinct aspects of cortical circuit dynamics date: 2019-10-02 journal: bioRxiv DOI: 10.1101/790410 sha: doc_id: 103041 cord_uid: ymr3e60k file: cache/cord-103181-my4n0vye.json key: cord-103181-my4n0vye authors: Valle-Casuso, José Carlos; Gaudaire, Delphine; Martin-Faivre, Lydie; Madeline, Anthony; Dallemagne, Patrick; Pronost, Stéphane; Munier-Lehmann, Hélène; Zientara, Stephan; Vidalain, Pierre-Olivier; Hans, Aymeric title: Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors date: 2020-04-10 journal: bioRxiv DOI: 10.1101/2020.04.10.035402 sha: doc_id: 103181 cord_uid: my4n0vye file: cache/cord-103112-m6cg67lz.json key: cord-103112-m6cg67lz authors: Schloer, Sebastian; Brunotte, Linda; Goretzko, Jonas; Mecate-Zambrano, Angeles; Korthals, Nadia; Gerke, Volker; Ludwig, Stephan; Rescher, Ursula title: Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.07.27.222836 sha: doc_id: 103112 cord_uid: m6cg67lz file: cache/cord-103108-vmze2mdx.json key: cord-103108-vmze2mdx authors: Vanheer, Lotte; Schiavo, Andrea Alex; Van Haele, Matthias; Haesen, Tine; Janiszewski, Adrian; Chappell, Joel; Roskams, Tania; Cnop, Miriam; Pasque, Vincent title: Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas date: 2020-09-25 journal: bioRxiv DOI: 10.1101/2020.09.23.310094 sha: doc_id: 103108 cord_uid: vmze2mdx file: cache/cord-103150-e9q8e62v.json key: cord-103150-e9q8e62v authors: Mishra, Shreya; Srivastava, Divyanshu; Kumar, Vibhor title: Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs date: 2020-11-04 journal: bioRxiv DOI: 10.1101/2020.07.24.219196 sha: doc_id: 103150 cord_uid: e9q8e62v file: cache/cord-103176-hfd8ur9a.json key: cord-103176-hfd8ur9a authors: Frost, H. Robert title: Variance-adjusted Mahalanobis (VAM): a fast and accurate method for cell-specific gene set scoring date: 2020-02-19 journal: bioRxiv DOI: 10.1101/2020.02.18.954321 sha: doc_id: 103176 cord_uid: hfd8ur9a file: cache/cord-103180-5hkoeca7.json key: cord-103180-5hkoeca7 authors: Furstenau, Tara N.; Cocking, Jill H.; Hepp, Crystal M.; Fofanov, Viacheslav Y. title: Sample pooling methods for efficient pathogen screening: Practical implications date: 2020-07-16 journal: bioRxiv DOI: 10.1101/2020.07.16.206060 sha: doc_id: 103180 cord_uid: 5hkoeca7 file: cache/cord-103157-xe5ccw9j.json key: cord-103157-xe5ccw9j authors: Mayer, David; Russell, Seth; Wilson, Melissa P.; Kahn, Michael G.; Wiley, Laura K. title: Developing and Deploying a Scalable Computing Platform to Support MOOC Education in Clinical Data Science date: 2020-08-27 journal: bioRxiv DOI: 10.1101/2020.08.27.270009 sha: doc_id: 103157 cord_uid: xe5ccw9j file: cache/cord-103029-nc5yf6x4.json key: cord-103029-nc5yf6x4 authors: Wichmann, Stefan; Scherer, Siegfried; Ardern, Zachary title: Computational design of genes encoding completely overlapping protein domains: Influence of genetic code and taxonomic rank date: 2020-09-25 journal: bioRxiv DOI: 10.1101/2020.09.25.312959 sha: doc_id: 103029 cord_uid: nc5yf6x4 file: cache/cord-103174-4m3ajc8a.json key: cord-103174-4m3ajc8a authors: Okada, Megan; Guo, Ping; Nalder, Shai-anne; Sigala, Paul A. title: Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity date: 2020-10-16 journal: bioRxiv DOI: 10.1101/2020.06.11.146407 sha: doc_id: 103174 cord_uid: 4m3ajc8a file: cache/cord-103163-0rreoh4o.json key: cord-103163-0rreoh4o authors: Smith, Sydni Caet; Gribble, Jennifer; Diller, Julia R.; Wiebe, Michelle A.; Thoner, Timothy W.; Denison, Mark R.; Ogden, Kristen M. title: Reovirus RNA recombination is sequence directed and generates internally deleted defective genome segments during passage date: 2020-10-22 journal: bioRxiv DOI: 10.1101/2020.10.19.346031 sha: doc_id: 103163 cord_uid: 0rreoh4o file: cache/cord-103204-gt6upfri.json key: cord-103204-gt6upfri authors: Hölzer, Martin; Marz, Manja title: PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection date: 2020-05-20 journal: bioRxiv DOI: 10.1101/2020.05.18.102731 sha: doc_id: 103204 cord_uid: gt6upfri file: cache/cord-103271-l9n27ocf.json key: cord-103271-l9n27ocf authors: Carozza, Jacqueline A; Brown, Jenifer A.; Böhnert, Volker; Fernandez, Daniel; AlSaif, Yasmeen; Mardjuki, Rachel E.; Smith, Mark; Li, Lingyin title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date: 2020-05-31 journal: bioRxiv DOI: 10.1101/2020.05.30.125534 sha: doc_id: 103271 cord_uid: l9n27ocf file: cache/cord-103208-krann2ir.json key: cord-103208-krann2ir authors: Barber-Axthelm, Isaac M; Kelly, Hannah G; Esterbauer, Robyn; Wragg, Kathleen; Gibbon, Anne; Lee, Wen Shi; Wheatley, Adam K; Kent, Stephen J; Tan, Hyon-Xhi; Juno, Jennifer A title: Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node date: 2020-08-29 journal: bioRxiv DOI: 10.1101/2020.08.27.270975 sha: doc_id: 103208 cord_uid: krann2ir file: cache/cord-103187-a255643n.json key: cord-103187-a255643n authors: Mitchell, Evan; Wild, Geoff title: Prophylactic host behaviour discourages pathogen exploitation date: 2019-12-19 journal: bioRxiv DOI: 10.1101/2019.12.18.881383 sha: doc_id: 103187 cord_uid: a255643n file: cache/cord-103249-k35o3gxe.json key: cord-103249-k35o3gxe authors: Johannsen, Leif; Potwar, Karna; Saveriano, Matteo; Endo, Satoshi; Lee, Dongheui title: Robotic light touch assists human balance control during maximum forward reaching date: 2019-11-20 journal: bioRxiv DOI: 10.1101/848432 sha: doc_id: 103249 cord_uid: k35o3gxe file: cache/cord-103294-1lrfna4v.json key: cord-103294-1lrfna4v authors: Northrop, Amanda C.; Avalone, Vanessa; Ellison, Aaron M.; Ballif, Bryan A.; Gotelli, Nicholas J. title: Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem date: 2020-05-02 journal: bioRxiv DOI: 10.1101/2020.05.01.073239 sha: doc_id: 103294 cord_uid: 1lrfna4v file: cache/cord-103301-v4l9sovt.json key: cord-103301-v4l9sovt authors: Bloom, David C.; Tran, Robert K.; Feller, Joyce; Voellmy, Richard title: Immunization by replication-competent controlled herpesvirus vectors date: 2018-04-11 journal: bioRxiv DOI: 10.1101/299230 sha: doc_id: 103301 cord_uid: v4l9sovt file: cache/cord-103363-efd80dgn.json key: cord-103363-efd80dgn authors: Mahan, Margaret; Rafter, Daniel; Casey, Hannah; Engelking, Marta; Abdallah, Tessneem; Truwit, Charles; Oswood, Mark; Samadani, Uzma title: tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports date: 2019-03-21 journal: bioRxiv DOI: 10.1101/585331 sha: doc_id: 103363 cord_uid: efd80dgn file: cache/cord-103343-k4v5ksvq.json key: cord-103343-k4v5ksvq authors: Naim, Nikki; Amrit, Francis RG; Ratnappan, Ramesh; DelBuono, Nicholas; Loose, Julia A; Ghazi, Arjumand title: NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity date: 2020-09-11 journal: bioRxiv DOI: 10.1101/2020.09.11.290452 sha: doc_id: 103343 cord_uid: k4v5ksvq file: cache/cord-103350-jj9pc4a6.json key: cord-103350-jj9pc4a6 authors: Tang, Pingtao; Das, Jharna R.; Li, Jinliang; Yu, Jing; Ray, Patricio E. title: An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy date: 2020-05-08 journal: bioRxiv DOI: 10.1101/2020.05.06.081851 sha: doc_id: 103350 cord_uid: jj9pc4a6 file: cache/cord-103306-1wc3f1rl.json key: cord-103306-1wc3f1rl authors: Sengupta, Sourodip; Addya, Sankar; Biswas, Diptomit; Sarma, Jayasri Das title: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine coronavirus-induced neuroinflammation date: 2020-09-18 journal: bioRxiv DOI: 10.1101/2020.09.17.302877 sha: doc_id: 103306 cord_uid: 1wc3f1rl file: cache/cord-103320-2rpr7aph.json key: cord-103320-2rpr7aph authors: Bhandari, Bikash K.; Gardner, Paul P.; Lim, Chun Shen title: Solubility-Weighted Index: fast and accurate prediction of protein solubility date: 2020-03-26 journal: bioRxiv DOI: 10.1101/2020.02.15.951012 sha: doc_id: 103320 cord_uid: 2rpr7aph file: cache/cord-103213-oinumv1z.json key: cord-103213-oinumv1z authors: Kalantar, Katrina L.; Carvalho, Tiago; de Bourcy, Charles F.A.; Dimitrov, Boris; Dingle, Greg; Egger, Rebecca; Han, Julie; Holmes, Olivia B.; Juan, Yun-Fang; King, Ryan; Kislyuk, Andrey; Mariano, Maria; Reynoso, Lucia V.; Cruz, David Rissato; Sheu, Jonathan; Tang, Jennifer; Wang, James; Zhang, Mark A.; Zhong, Emily; Ahyong, Vida; Lay, Sreyngim; Chea, Sophana; Bohl, Jennifer A.; Manning, Jessica E.; Tato, Cristina M.; DeRisi, Joseph L. title: IDseq – An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring date: 2020-04-18 journal: bioRxiv DOI: 10.1101/2020.04.07.030551 sha: doc_id: 103213 cord_uid: oinumv1z file: cache/cord-103408-vhrlrd2c.json key: cord-103408-vhrlrd2c authors: Mishra, Preet; Prasad, Abhishek; Babu, Suresh; Yadav, Gitanjali title: Decision Support Systems based on Scientific Evidence: Bibliometric Networks of Invasive Lantana camara date: 2020-08-10 journal: bioRxiv DOI: 10.1101/2020.08.10.240879 sha: doc_id: 103408 cord_uid: vhrlrd2c file: cache/cord-103377-j1mmx7k7.json key: cord-103377-j1mmx7k7 authors: Karasik, Agnes; Jones, Grant D.; DePass, Andrew V.; Guydosh, Nicholas R. title: Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences date: 2020-09-11 journal: bioRxiv DOI: 10.1101/2020.09.10.291690 sha: doc_id: 103377 cord_uid: j1mmx7k7 file: cache/cord-103396-jiuqk6kg.json key: cord-103396-jiuqk6kg authors: Adler, Paul N. title: Short distance non-autonomy and intercellular transfer of chitin synthase in Drosophila date: 2020-05-26 journal: bioRxiv DOI: 10.1101/2020.05.24.113803 sha: doc_id: 103396 cord_uid: jiuqk6kg file: cache/cord-103465-6udhvl9n.json key: cord-103465-6udhvl9n authors: Schierding, William; Horsfield, Julia; O’Sullivan, Justin title: Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date: 2020-04-13 journal: bioRxiv DOI: 10.1101/2020.04.11.037358 sha: doc_id: 103465 cord_uid: 6udhvl9n file: cache/cord-103504-ucqqpra5.json key: cord-103504-ucqqpra5 authors: Zhang, Zhe; Luo, Shuo; Barbosa, Guilherme Oliveira; Bai, Meirong; Kornberg, Thomas B.; Ma, Dengke K. title: The conserved ER-transmembrane protein TMEM39 coordinates with COPII to promote collagen secretion and prevent ER stress date: 2020-09-20 journal: bioRxiv DOI: 10.1101/2020.08.17.253450 sha: doc_id: 103504 cord_uid: ucqqpra5 file: cache/cord-103345-v555a2ll.json key: cord-103345-v555a2ll authors: Taylor, Adrian; Grapentine, Sophie; Ichhpuniani, Jasmine; Bakovic, Marica title: The novel roles of choline transporter-like 1 and 2 in ethanolamine transport date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.08.27.270223 sha: doc_id: 103345 cord_uid: v555a2ll file: cache/cord-103430-x6zzuu7v.json key: cord-103430-x6zzuu7v authors: Contu, Lara; Balistreri, Giuseppe; Domanski, Michal; Uldry, Anne-Christine; Mühlemann, Oliver title: Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.10.12.335497 sha: doc_id: 103430 cord_uid: x6zzuu7v file: cache/cord-103435-yufvt44t.json key: cord-103435-yufvt44t authors: van Aalst, Marvin; Ebenhöh, Oliver; Matuszyńska, Anna title: Constructing and analysing dynamic models with modelbase v1.0 - a software update date: 2020-10-02 journal: bioRxiv DOI: 10.1101/2020.09.30.321380 sha: doc_id: 103435 cord_uid: yufvt44t file: cache/cord-103341-q7yqnvm2.json key: cord-103341-q7yqnvm2 authors: MacPherson, Ailene; Louca, Stilianos; McLaughlin, Angela; Joy, Jeffrey B.; Pennell, Matthew W. title: A General Birth-Death-Sampling Model for Epidemiology and Macroevolution date: 2020-10-11 journal: bioRxiv DOI: 10.1101/2020.10.10.334383 sha: doc_id: 103341 cord_uid: q7yqnvm2 file: cache/cord-103502-asphso2s.json key: cord-103502-asphso2s authors: Herrgårdh, Tilda; Li, Hao; Nyman, Elin; Cedersund, Gunnar title: An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow date: 2020-10-21 journal: bioRxiv DOI: 10.1101/2020.10.21.344499 sha: doc_id: 103502 cord_uid: asphso2s file: cache/cord-103417-2uinislh.json key: cord-103417-2uinislh authors: Doi, Hideyuki; Watanabe, Takeshi; Nishizawa, Naofumi; Saito, Tatsuya; Nagata, Hisao; Kameda, Yuichi; Maki, Nobutaka; Ikeda, Kousuke; Fukuzawa, Takashi title: On-site eDNA detection of species using ultra-rapid mobile PCR date: 2020-10-01 journal: bioRxiv DOI: 10.1101/2020.09.28.314625 sha: doc_id: 103417 cord_uid: 2uinislh file: cache/cord-103460-5thh6syt.json key: cord-103460-5thh6syt authors: Carlson, Colin J.; Albery, Gregory F.; Merow, Cory; Trisos, Christopher H.; Zipfel, Casey M.; Eskew, Evan A.; Olival, Kevin J.; Ross, Noam; Bansal, Shweta title: Climate change will drive novel cross-species viral transmission date: 2020-07-14 journal: bioRxiv DOI: 10.1101/2020.01.24.918755 sha: doc_id: 103460 cord_uid: 5thh6syt file: cache/cord-103297-4stnx8dw.json key: cord-103297-4stnx8dw authors: Widrich, Michael; Schäfl, Bernhard; Pavlović, Milena; Ramsauer, Hubert; Gruber, Lukas; Holzleitner, Markus; Brandstetter, Johannes; Sandve, Geir Kjetil; Greiff, Victor; Hochreiter, Sepp; Klambauer, Günter title: Modern Hopfield Networks and Attention for Immune Repertoire Classification date: 2020-08-17 journal: bioRxiv DOI: 10.1101/2020.04.12.038158 sha: doc_id: 103297 cord_uid: 4stnx8dw key: cord-193356-hqbstgg7 authors: Widrich, Michael; Schafl, Bernhard; Ramsauer, Hubert; Pavlovi'c, Milena; Gruber, Lukas; Holzleitner, Markus; Brandstetter, Johannes; Sandve, Geir Kjetil; Greiff, Victor; Hochreiter, Sepp; Klambauer, Gunter title: Modern Hopfield Networks and Attention for Immune Repertoire Classification date: 2020-07-16 journal: nan DOI: nan sha: doc_id: 193356 cord_uid: hqbstgg7 file: cache/cord-103358-1hbw3yo3.json key: cord-103358-1hbw3yo3 authors: Gisbert-Muñoz, Sandra; Quiñones, Ileana; Amoruso, Lucia; Timofeeva, Polina; Geng, Shuang; Boudelaa, Sami; Pomposo, Iñigo; Gil-Robles, Santiago; Carreiras, Manuel title: MULTIMAP: Multilingual picture naming test for mapping eloquent areas during awake surgeries date: 2020-06-08 journal: bioRxiv DOI: 10.1101/2020.02.20.957282 sha: doc_id: 103358 cord_uid: 1hbw3yo3 file: cache/cord-103422-ys846i99.json key: cord-103422-ys846i99 authors: Xu, Xinhui; Luo, Tao; Gao, Jinliang; Lin, Na; Li, Weiwei; Xia, Xinyi; Wang, Jinke title: CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date: 2020-05-13 journal: bioRxiv DOI: 10.1101/2020.05.13.093062 sha: doc_id: 103422 cord_uid: ys846i99 file: cache/cord-103511-31njndob.json key: cord-103511-31njndob authors: Broggi, Achille; 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Ning, Kang; Wang, Xiaomei; Wang, Jianke; Cheng, Fang; Ganaie, Safder S.; Tavis, John E.; Qiu, Jianming title: Establishment of a Replicon System for Bourbon Virus and Identification of Small Molecules that Efficiently Inhibit Virus Replication date: 2020-04-25 journal: bioRxiv DOI: 10.1101/2020.04.24.058693 sha: doc_id: 103524 cord_uid: 1w9tdhdd file: cache/cord-103432-cdmoazrl.json key: cord-103432-cdmoazrl authors: Richardson, Eve; Galson, Jacob D.; Kellam, Paul; Kelly, Dominic F.; Smith, Sarah E.; Palser, Anne; Watson, Simon; Deane, Charlotte M. title: A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies date: 2020-06-02 journal: bioRxiv DOI: 10.1101/2020.06.02.121129 sha: doc_id: 103432 cord_uid: cdmoazrl file: cache/cord-103462-z3d9lcar.json key: cord-103462-z3d9lcar authors: Wang, Shiyu; Wang, Longlong; Liu, Ya title: CD4+ T cell subsets present stable relationships in their T cell receptor repertoires date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.11.01.364224 sha: doc_id: 103462 cord_uid: z3d9lcar file: cache/cord-103497-1ls2dvzy.json key: cord-103497-1ls2dvzy authors: Ganier, C; Du-Harpur, X; Harun, N; Wan, B; Arthurs, C; Luscombe, NM; Watt, FM; Lynch, MD title: CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.29.123513 sha: doc_id: 103497 cord_uid: 1ls2dvzy file: cache/cord-103567-nh9i28lu.json key: cord-103567-nh9i28lu authors: Vanachayangkul, Pattaraporn; Im-erbsin, Rawiwan; Tungtaeng, Anchalee; Kodchakorn, Chanikarn; Roth, Alison; Adams, John; Chaisatit, Chaiyaporn; Saingam, Piyaporn; Sciotti, Richard J.; Reichard, Gregory A.; Nolan, Christina K.; Pybus, Brandon S.; Black, Chad C.; Lugo, Luis A.; Wegner, Matthew D.; Smith, Philip L.; Wojnarski, Mariusz; Vesely, Brian A.; Kobylinski, Kevin C. title: Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques date: 2020-04-29 journal: bioRxiv DOI: 10.1101/2020.04.27.065409 sha: doc_id: 103567 cord_uid: nh9i28lu file: cache/cord-103448-xa5zgkd3.json key: cord-103448-xa5zgkd3 authors: Adachi, Hiroaki; 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Jones, James Holland title: Coupled Dynamics of Behavior and Disease Contagion Among Antagonistic Groups date: 2020-10-05 journal: bioRxiv DOI: 10.1101/2020.06.17.157511 sha: doc_id: 103538 cord_uid: vh6ma7k7 file: cache/cord-103540-x18pz2uz.json key: cord-103540-x18pz2uz authors: Yellman, Christopher M. title: Precise replacement of Saccharomyces cerevisiae proteasome genes with human orthologs by an integrative targeting method date: 2020-03-26 journal: bioRxiv DOI: 10.1101/2020.03.25.006262 sha: doc_id: 103540 cord_uid: x18pz2uz file: cache/cord-103618-cl7evbr3.json key: cord-103618-cl7evbr3 authors: Wang, Yingxue; Zhang, Weijiao; Jefferson, Matthew; Sharma, Parul; Bone, Ben; Kipar, Anja; Coombes, Janine L.; Pearson, Timothy; Man, Angela; Zhekova, Alex; Bao, Yongping; Tripp, Ralph A; Yamauchi, Yohei; Carding, Simon R.; Mayer, Ulrike; Powell, Penny P.; Stewart, James P.; Wileman, Thomas title: The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal respiratory infection by influenza A virus at epithelial surfaces date: 2020-05-07 journal: bioRxiv DOI: 10.1101/2020.01.15.907873 sha: doc_id: 103618 cord_uid: cl7evbr3 file: cache/cord-103517-1itisiup.json key: cord-103517-1itisiup authors: Kwesi-Maliepaard, Eliza Mari; 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Higginson, Jill; Jeka, John title: Walking cadence affects the recruitment of the medial-lateral balance mechanisms date: 2019-06-03 journal: bioRxiv DOI: 10.1101/658070 sha: doc_id: 103606 cord_uid: 5gbk6t6y file: cache/cord-103542-mf721oa9.json key: cord-103542-mf721oa9 authors: Mazhari, Ramin; Brewster, Jessica; Fong, Rich; Bourke, Caitlin; Liu, Zoe SJ; Takashima, Eizo; Tsuboi, Takafumi; Tham, Wai-Hong; Harbers, Matthias; Chitnis, Chetan; Healer, Julie; Ome-Kaius, Maria; Sattabongkot, Jetsumon; Kazura, James; Robinson, Leanne J.; King, Christopher; Mueller, Ivo; Longley, Rhea J. title: A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against P. vivax antigens in a multiplexed bead-based assay using Luminex® technology (Bio-Plex® 200 or MAGPIX®) date: 2020-08-10 journal: bioRxiv DOI: 10.1101/2020.08.10.243980 sha: doc_id: 103542 cord_uid: mf721oa9 file: cache/cord-103648-g50g17ti.json key: cord-103648-g50g17ti authors: Wang, Hao-Yuan; Oltion, Keely; Al-Khdhairawi, Amjad Ayad Qatran; Weber, Jean-Frédéric F.; Taunton, Jack title: Total synthesis and biological characterization of SR-A3, a ternatin-related eEF1A inhibitor with enhanced cellular residence time date: 2020-10-08 journal: bioRxiv DOI: 10.1101/2020.10.06.325498 sha: doc_id: 103648 cord_uid: g50g17ti file: cache/cord-103528-3tib5o1m.json key: cord-103528-3tib5o1m authors: Ahmed, Asad; Mam, Bhavika; Sowdhamini, Ramanathan title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date: 2020-09-28 journal: bioRxiv DOI: 10.1101/2020.09.28.316224 sha: doc_id: 103528 cord_uid: 3tib5o1m file: cache/cord-103568-zesg4atp.json key: cord-103568-zesg4atp authors: Iacullo, Carly; Diesburg, Darcy A.; Wessel, Jan R. title: Non-selective inhibition of the motor system following unexpected and expected infrequent events date: 2020-03-26 journal: bioRxiv DOI: 10.1101/2020.03.25.008789 sha: doc_id: 103568 cord_uid: zesg4atp file: cache/cord-103580-6rf1xs0d.json key: cord-103580-6rf1xs0d authors: Arokiaraj, Mark Christopher; Wilson, Jarad title: A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate date: 2020-05-15 journal: bioRxiv DOI: 10.1101/2020.05.13.082180 sha: doc_id: 103580 cord_uid: 6rf1xs0d file: cache/cord-103592-lkngp2u6.json key: cord-103592-lkngp2u6 authors: Bachmaier, Kurt; Stuart, Andrew; Hong, Zhigang; Tsukasaki, Yoshikazu; Singh, Abhalaxmi; Chakraborty, Sreeparna; Mukhopadhyay, Amitabha; Gao, Xiaopei; Maienschein-Cline, Mark; Kanteti, Prasad; Rehman, Jalees; Malik, Asrar B. title: Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date: 2020-07-02 journal: bioRxiv DOI: 10.1101/2020.06.30.180927 sha: doc_id: 103592 cord_uid: lkngp2u6 file: cache/cord-103688-n7hzpbyf.json key: cord-103688-n7hzpbyf authors: Wang, Lina; Chen, Fengzhen; Guo, Xueqin; You, Lijin; Yang, Xiaoxia; Yang, Fan; Yang, Tao; Gao, Fei; Hua, Cong; Ding, Yuantong; Cai, Jia; Yang, Linlin; Huang, Wei; Xu, Zhicheng; Wan, Bo; Tong, Jiawei; Peng, Chunhua; Yang, Yawen; Zhang, Lei; Liu, Ke; Zhou, Feiyu; Zhang, Minwen; Tan, Cong; Zeng, Wenjun; Wang, Bo; Wei, Xiaofeng title: VirusDIP: Virus Data Integration Platform date: 2020-06-09 journal: bioRxiv DOI: 10.1101/2020.06.08.139451 sha: doc_id: 103688 cord_uid: n7hzpbyf file: cache/cord-103523-46hn2249.json key: cord-103523-46hn2249 authors: Shaw, Dario R.; Ali, Muhammad; Katuri, Krishna P.; Gralnick, Jeffrey A.; Reimann, Joachim; Mesman, Rob; van Niftrik, Laura; Jetten, Mike S. M.; Saikaly, Pascal E. title: Extracellular electron transfer-dependent anaerobic oxidation of ammonium by anammox bacteria date: 2019-11-26 journal: bioRxiv DOI: 10.1101/855817 sha: doc_id: 103523 cord_uid: 46hn2249 file: cache/cord-103625-p55ew8w7.json key: cord-103625-p55ew8w7 authors: Ramana, Chilakamarti V. title: Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.08.14.244897 sha: doc_id: 103625 cord_uid: p55ew8w7 file: cache/cord-103714-06hhlma3.json key: cord-103714-06hhlma3 authors: Miller, Mariël; Rogers, Jeffery C.; Badham, Marissa A.; Cadenas, Lousili; Brightwell, Eian; Adams, Jacob; Tyler, Cole; Sebahar, Paul R.; Haussener, Travis J.; Reddy, Hariprassada K.; Looper, Ryan E.; Williams, Dustin L. title: Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms date: 2020-06-04 journal: bioRxiv DOI: 10.1101/2020.06.04.133934 sha: doc_id: 103714 cord_uid: 06hhlma3 file: cache/cord-103652-yjl7uj2h.json key: cord-103652-yjl7uj2h authors: Vickaryous, Nicola; Jitlal, Mark; Jacobs, Benjamin Meir; Middleton, Rod; Chandran, Siddharthan; MacDougall, Niall John James; Giovannoni, Gavin; Dobson, Ruth title: Remote testing of vitamin D levels across the UK MS population – a case control study date: 2020-10-16 journal: bioRxiv DOI: 10.1101/2020.10.16.342253 sha: doc_id: 103652 cord_uid: yjl7uj2h file: cache/cord-103638-n5kpvsvg.json key: cord-103638-n5kpvsvg authors: Nguyen, Long T.; Smith, Brianna M.; Jain, Piyush K. title: Enhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.13.036079 sha: doc_id: 103638 cord_uid: n5kpvsvg file: cache/cord-103739-mmkrwj8t.json key: cord-103739-mmkrwj8t authors: Snijder, Eric J.; Limpens, Ronald W.A.L.; de Wilde, Adriaan H.; de Jong, Anja W. M.; Zevenhoven-Dobbe, Jessika C.; Maier, Helena J.; Faas, Frank F.G.A.; Koster, Abraham J.; Bárcena, Montserrat title: A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis date: 2020-03-24 journal: bioRxiv DOI: 10.1101/2020.03.24.005298 sha: doc_id: 103739 cord_uid: mmkrwj8t file: cache/cord-103674-pmbpx162.json key: cord-103674-pmbpx162 authors: Kalaycı, Salih; Özden, Cihan title: The Linkage among Sea Transportation, Trade Liberalization and Industrial Development in the context of Carbon Dioxide Emissions: An Empirical Investigation from China date: 2020-07-13 journal: bioRxiv DOI: 10.1101/2020.07.13.200386 sha: doc_id: 103674 cord_uid: pmbpx162 file: cache/cord-103781-bycskjtr.json key: cord-103781-bycskjtr authors: Mönke, Gregor; Sorgenfrei, Frieda A.; Schmal, Christoph; Granada, Adrián E. title: Optimal time frequency analysis for biological data - pyBOAT date: 2020-06-04 journal: bioRxiv DOI: 10.1101/2020.04.29.067744 sha: doc_id: 103781 cord_uid: bycskjtr file: cache/cord-103733-blam1f4c.json key: cord-103733-blam1f4c authors: Levade, Inès; Saber, Morteza M.; Midani, Firas; Chowdhury, Fahima; Khan, Ashraful I.; Begum, Yasmin A.; Ryan, Edward T.; David, Lawrence A.; Calderwood, Stephen B.; Harris, Jason B.; LaRocque, Regina C.; Qadri, Firdausi; Shapiro, B. Jesse; Weil, Ana A. title: Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.02.25.960930 sha: doc_id: 103733 cord_uid: blam1f4c file: cache/cord-103703-t03r6ny8.json key: cord-103703-t03r6ny8 authors: Nguyen-Tu, Marie-Sophie; Martinez-Sanchez, Aida; Leclerc, Isabelle; Rutter, Guy A.; da Silva Xavier, Gabriela title: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice date: 2020-05-20 journal: bioRxiv DOI: 10.1101/2020.05.18.102384 sha: doc_id: 103703 cord_uid: t03r6ny8 file: cache/cord-103597-mt0h06y3.json key: cord-103597-mt0h06y3 authors: Muller, Alana; Sirianni, Lindsey A.; Addante, Richard J. title: Neurophysiological Correlates of the Dunning-Kruger Effect date: 2020-05-20 journal: bioRxiv DOI: 10.1101/2019.12.26.888511 sha: doc_id: 103597 cord_uid: mt0h06y3 file: cache/cord-103735-nil1vv6h.json key: cord-103735-nil1vv6h authors: Alfano, Niccolo; Dayaram, Anisha; Axtner, Jan; Tsangaras, Kyriakos; Kampmann, Marie-Louise; Mohamed, Azlan; Wong, Seth T.; Gilbert, M. Thomas P.; Wilting, Andreas; Greenwood, Alex D. title: Non-invasive surveys of mammalian viruses using environmental DNA date: 2020-03-29 journal: bioRxiv DOI: 10.1101/2020.03.26.009993 sha: doc_id: 103735 cord_uid: nil1vv6h file: cache/cord-103773-1b961lfz.json key: cord-103773-1b961lfz authors: Kurokawa, Shunji; Hashimoto, Yoshihide; Funamoto, Seiichi; Yamashita, Akitatsu; Yamazaki, Kazuhiro; Ikeda, Tadashi; Minatoya, Kenji; Kishida, Akio; Masumoto, Hidetoshi title: In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.29.123018 sha: doc_id: 103773 cord_uid: 1b961lfz file: cache/cord-103654-k02z72gb.json key: cord-103654-k02z72gb authors: Gamboa Arana, Olga Lucia; Palmer, Hannah; Dannhauer, Moritz; Hile, Connor; Liu, Sicong; Hamdan, Rena; Brito, Alexandra; Cabeza, Roberto; Davis, Simon W.; Peterchev, Angel V.; Sommer, Marc A.; Appelbaum, Lawrence G. title: Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex date: 2020-06-15 journal: bioRxiv DOI: 10.1101/2020.06.14.151118 sha: doc_id: 103654 cord_uid: k02z72gb file: cache/cord-103715-53v1qoyc.json key: cord-103715-53v1qoyc authors: Bauman, Neda; Ilić, Andjelija; Lijeskić, Olivera; Uzelac, Aleksandra; Klun, Ivana; Srbljanović, Jelena; Ćirković, Vladimir; Bobić, Branko; Štajner, Tijana; Djurković-Djaković, Olgica title: Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts date: 2020-05-21 journal: bioRxiv DOI: 10.1101/2020.05.21.108118 sha: doc_id: 103715 cord_uid: 53v1qoyc file: cache/cord-103872-yzqic5vt.json key: cord-103872-yzqic5vt authors: Liu, Zhijin title: Global view on virus infection in non-human primates and implication for public health and wildlife conservation date: 2020-05-13 journal: bioRxiv DOI: 10.1101/2020.05.12.089961 sha: doc_id: 103872 cord_uid: yzqic5vt file: cache/cord-103812-ls6zgipi.json key: cord-103812-ls6zgipi authors: Norris, Rachael P.; Terasaki, Mark title: Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.06.29.178475 sha: doc_id: 103812 cord_uid: ls6zgipi file: cache/cord-103757-fed21fhu.json key: cord-103757-fed21fhu authors: McPherson, Malinda J.; McDermott, Josh H. title: Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory date: 2020-10-15 journal: bioRxiv DOI: 10.1101/2020.05.07.082511 sha: doc_id: 103757 cord_uid: fed21fhu file: cache/cord-103802-mygo3qx0.json key: cord-103802-mygo3qx0 authors: Li, Yanpeng; Gordon, Emilia; Idle, Amanda; Altan, Eda; Seguin, M. 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J.; von Knethen, Andreas; Jirkof, Paulin; Keubler, Lydia; Bleich, André; Häger, Christine title: One score to rule them all: severity assessment in laboratory mice date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.06.23.166801 sha: doc_id: 103788 cord_uid: sxw4l9tt file: cache/cord-103914-ppgx7mci.json key: cord-103914-ppgx7mci authors: Maughan, Elizabeth F.; Nigro, Ersilia; Pennycuick, Adam; Gowers, Kate H.C.; Denais, Celine; Gómez-López, Sandra; Lazarus, Kyren A.; Butler, Colin R.; Lee, Dani Do Hyang; Orr, Jessica C.; Teixeira, Vitor H.; Hartley, Benjamin E.; Hewitt, Richard J.; Yaghchi, Chadwan Al; Sandhu, Gurpreet S.; Birchall, Martin A.; O’Callaghan, Christopher; Smith, Claire M.; De Coppi, Paolo; Hynds, Robert E.; Janes, Sam M. title: Cell-intrinsic differences between human airway epithelial cells from children and adults date: 2020-04-20 journal: bioRxiv DOI: 10.1101/2020.04.20.027144 sha: doc_id: 103914 cord_uid: ppgx7mci file: cache/cord-103925-i73ymrov.json key: cord-103925-i73ymrov authors: Hill, Chris H.; Cook, Georgia; Napthine, Sawsan; Kibe, Anuja; Brown, Katherine; Caliskan, Neva; Firth, Andrew E.; Graham, Stephen C.; Brierley, Ian title: Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus date: 2020-08-11 journal: bioRxiv DOI: 10.1101/2020.08.11.245068 sha: doc_id: 103925 cord_uid: i73ymrov file: cache/cord-103853-ar09nzmw.json key: cord-103853-ar09nzmw authors: Wayment-Steele, Hannah K.; Kladwang, Wipapat; Das, Rhiju title: RNA secondary structure packages ranked and improved by high-throughput experiments date: 2020-05-31 journal: bioRxiv DOI: 10.1101/2020.05.29.124511 sha: doc_id: 103853 cord_uid: ar09nzmw file: cache/cord-103888-ggm29vrz.json key: cord-103888-ggm29vrz authors: Nova, Nicole; Deyle, Ethan R.; Shocket, Marta S.; MacDonald, Andrew J.; Childs, Marissa L.; Rypdal, Martin; Sugihara, George; Mordecai, Erin A. title: Susceptible host availability modulates climate effects on dengue dynamics date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2019.12.20.883363 sha: doc_id: 103888 cord_uid: ggm29vrz file: cache/cord-104008-luqvw0y8.json key: cord-104008-luqvw0y8 authors: Levinson, Julia; Kohl, Kid; Baltag, Valentina; Ross, David title: Investigating the effectiveness of school health services delivered by a health provider: a systematic review of systematic reviews date: 2019-02-07 journal: bioRxiv DOI: 10.1101/543868 sha: doc_id: 104008 cord_uid: luqvw0y8 file: cache/cord-103940-a2cqw8kg.json key: cord-103940-a2cqw8kg authors: Shi, Yuejun; Shi, Jiale; Sun, Limeng; Tan, Yubei; Wang, Gang; Guo, Fenglin; Hu, Guangli; Fu, Yanan; Fu, Zhen F.; Xiao, Shaobo; Peng, Guiqing title: Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins date: 2020-06-09 journal: bioRxiv DOI: 10.1101/2020.06.09.141580 sha: doc_id: 103940 cord_uid: a2cqw8kg file: cache/cord-103964-k6jnv87v.json key: cord-103964-k6jnv87v authors: Friedl, Jana; Knopp, Michael R.; Groh, Carina; Paz, Eyal; Gould, Sven B.; Boos, Felix; Herrmann, Johannes M. title: More than just a ticket canceller: The mitochondrial processing peptidase matures complex precursor proteins at internal cleavage sites date: 2020-07-03 journal: bioRxiv DOI: 10.1101/2020.07.02.183996 sha: doc_id: 103964 cord_uid: k6jnv87v file: cache/cord-103892-v6gkubd4.json key: cord-103892-v6gkubd4 authors: Mäkinen, Janne J.; Shin, Yeonoh; Vieras, Eeva; Virta, Pasi; Metsä-Ketelä, Mikko; Murakami, Katsuhiko S.; Belogurov, Georgiy A. title: The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.06.30.179606 sha: doc_id: 103892 cord_uid: v6gkubd4 file: cache/cord-104035-ykyr2gvl.json key: cord-104035-ykyr2gvl authors: Ivanov, Mark V.; Bubis, Julia A.; Gorshkov, Vladimir; Abdrakhimov, Daniil A.; Kjeldsen, Frank; Gorshkov, Mikhail V. title: Boosting the MS1-only proteomics with machine learning allows 2000 protein identifications in 5-minute proteome analysis date: 2020-10-29 journal: bioRxiv DOI: 10.1101/2020.10.29.359075 sha: doc_id: 104035 cord_uid: ykyr2gvl file: cache/cord-104122-klvx927g.json key: cord-104122-klvx927g authors: Tayfuroglu, Omer; Yildiz, Muslum; Pearson, Lee-Wright; Kocak, Abdulkadir title: An Accurate Free Energy Method for Solvation of Organic Compounds and Binding to Proteins date: 2020-05-28 journal: bioRxiv DOI: 10.1101/2020.05.26.116459 sha: doc_id: 104122 cord_uid: klvx927g file: cache/cord-103915-rzy7mejb.json key: cord-103915-rzy7mejb authors: Duricki, Denise A.; Drndarski, Svetlana; Bernanos, Michel; Wood, Tobias; Bosch, Karen; Chen, Qin; Shine, H. 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Torres; Abdala-Valencia, Hiam; Politanska, Yuliya; Singer, Benjamin D. title: Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date: 2020-06-05 journal: bioRxiv DOI: 10.1101/2020.06.05.135194 sha: doc_id: 104030 cord_uid: eb29t38n file: cache/cord-104142-0nfprn2a.json key: cord-104142-0nfprn2a authors: Azmi, Maryam A.; Palmisano, Nicholas J.; Medwig-Kinney, Taylor N.; Moore, Frances E.; Rahman, Rumana; Zhang, Wan; Adikes, Rebecca C.; Matus, David Q. title: A laboratory module that explores RNA interference and codon optimization through fluorescence microscopy using Caenorhabditis elegans date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2020.10.17.344069 sha: doc_id: 104142 cord_uid: 0nfprn2a file: cache/cord-104001-5clslvqb.json key: cord-104001-5clslvqb authors: Wang, Xiaoqi; Yang, Yaning; Liao, Xiangke; Li, Lenli; Li, Fei; Peng, Shaoliang title: selfRL: Two-Level Self-Supervised Transformer Representation Learning for Link Prediction of Heterogeneous Biomedical Networks date: 2020-10-21 journal: bioRxiv DOI: 10.1101/2020.10.20.347153 sha: doc_id: 104001 cord_uid: 5clslvqb file: cache/cord-104055-47ren7ie.json key: cord-104055-47ren7ie authors: Lutkenhoff, Evan S.; Nigri, Anna; Sebastiano, Davide Rossi; Sattin, Davide; Visani, Elisa; Rosazza, Cristina; D’Incerti, Ludovico; Bruzzone, Maria Grazia; Franceschetti, Silvana; Leonardi, Matilde; Ferraro, Stefania; Monti, Martin M. title: EEG power spectra and subcortical pathology in chronic disorders of consciousness date: 2020-09-01 journal: bioRxiv DOI: 10.1101/695288 sha: doc_id: 104055 cord_uid: 47ren7ie file: cache/cord-103868-iwpiti2h.json key: cord-103868-iwpiti2h authors: Harrison, Angela R.; Moseley, Gregory W. title: The Ebola virus interferon antagonist VP24 undergoes active nucleocytoplasmic trafficking date: 2020-08-11 journal: bioRxiv DOI: 10.1101/2020.08.10.245563 sha: doc_id: 103868 cord_uid: iwpiti2h file: cache/cord-104031-vodwptdo.json key: cord-104031-vodwptdo authors: Altshuler, Anna; Amitai-Lange, Aya; Tarazi, Noam; Dey, Sunanda; Strinkovsky, Lior; Bhattacharya, Swarnabh; Hadad-Porat, Shira; Nasser, Waseem; Imeri, Jusuf; Ben-David, Gil; Tiosano, Beatrice; Berkowitz, Eran; Karin, Nathan; Savir, Yonatan; Shalom-Feuerstein, Ruby title: Capturing limbal epithelial stem cell population dynamics, signature, and their niche date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.06.30.179754 sha: doc_id: 104031 cord_uid: vodwptdo file: cache/cord-104109-k36jya0b.json key: cord-104109-k36jya0b authors: Das Jana, Indrani; Kumbhakar, Partha; Banerjee, Saptarshi; Gowda, Chinmayee Chowde; Kedia, Nandita; Kuila, Saikat Kumar; Banerjee, Sushanta; Das, Narayan Chandra; Das, Amit Kumar; Manna, Indranil; Tiwary, Chandra Sekhar; Mondal, Arindam title: Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus date: 2020-09-02 journal: bioRxiv DOI: 10.1101/2020.09.02.279737 sha: doc_id: 104109 cord_uid: k36jya0b file: cache/cord-104138-qagyaegp.json key: cord-104138-qagyaegp authors: Magee, Michelle; Lewis, Courtney; Noffs, Gustavo; Reece, Hannah; Chan, Jess C. S.; Zaga, Charissa J.; Paynter, Camille; Birchall, Olga; Azocar, Sandra Rojas; Ediriweera, Angela; Caverlé, Marja W.; Schultz, Benjamin G.; Vogel, Adam P. title: Effects of face masks on acoustic analysis and speech perception: Implications for peri-pandemic protocols date: 2020-10-08 journal: bioRxiv DOI: 10.1101/2020.10.06.327452 sha: doc_id: 104138 cord_uid: qagyaegp file: cache/cord-104157-rivaoo73.json key: cord-104157-rivaoo73 authors: Noreika, Valdas; Kamke, Marc R.; Canales-Johnson, Andrés; Chennu, Srivas; Bekinschtein, Tristan A.; Mattingley, Jason B. title: Alertness fluctuations during task performance modulate cortical evoked responses to transcranial magnetic stimulation date: 2019-06-28 journal: bioRxiv DOI: 10.1101/155754 sha: doc_id: 104157 cord_uid: rivaoo73 file: cache/cord-104162-fe51v2pt.json key: cord-104162-fe51v2pt authors: Zhang, Chiyu; Forsdyke, Donald R. title: Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.10.22.343673 sha: doc_id: 104162 cord_uid: fe51v2pt file: cache/cord-104140-o46kvd0b.json key: cord-104140-o46kvd0b authors: McPherson, Malinda J.; Grace, River C.; McDermott, Josh H. title: Harmonicity aids hearing in noise date: 2020-09-30 journal: bioRxiv DOI: 10.1101/2020.09.30.321000 sha: doc_id: 104140 cord_uid: o46kvd0b file: cache/cord-104092-yau3r79c.json key: cord-104092-yau3r79c authors: Tamming, Renee J.; Dumeaux, Vanessa; Langlois, Luana; Ellegood, Jacob; Qiu, Lily R.; Jiang, Yan; Lerch, Jason P.; Bérubé, Nathalie G. title: Atrx deletion in neurons leads to sexually-dimorphic dysregulation of miR-137 and spatial learning and memory deficits date: 2019-04-13 journal: bioRxiv DOI: 10.1101/606442 sha: doc_id: 104092 cord_uid: yau3r79c file: cache/cord-252910-7qvnj6c8.json key: cord-252910-7qvnj6c8 authors: Li, Xin; Jin, Xiufeng; Chen, Shunmei; Wang, Liangge; Yau, Tung On; Yang, Jianyi; Hong, Zhangyong; Ruan, Jishou; Duan, Guangyou; Gao, Shan title: The discovery of a recombinant SARS2-like CoV strain provides insights into SARS and COVID-19 pandemics date: 2020-09-21 journal: bioRxiv DOI: 10.1101/2020.07.22.213926 sha: doc_id: 252910 cord_uid: 7qvnj6c8 file: cache/cord-104146-pabh3ajb.json key: cord-104146-pabh3ajb authors: de Lussanet de la Sablonière, Marc H. 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S.; Bui, K. H.; Vargas, J. title: Local computational methods to improve the interpretability and analysis of cryo-EM maps date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.05.11.088013 sha: doc_id: 252097 cord_uid: 4kslllaq file: cache/cord-254855-gmy9zyad.json key: cord-254855-gmy9zyad authors: He, Sijia; Waheed, Abdul A.; Hetrick, Brian; Dabbagh, Deemah; Akhrymuk, Ivan V.; Kehn-Hall, Kylene; Freed, Eric O.; Wu, Yuntao title: PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity date: 2020-07-06 journal: bioRxiv DOI: 10.1101/2020.05.01.073387 sha: doc_id: 254855 cord_uid: gmy9zyad file: cache/cord-104073-vsa5y7ip.json key: cord-104073-vsa5y7ip authors: Warner, Emily F.; Bohálová, Natália; Brázda, Václav; Waller, Zoë A. E.; Bidula, Stefan title: Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date: 2020-09-23 journal: bioRxiv DOI: 10.1101/2020.09.23.310581 sha: doc_id: 104073 cord_uid: vsa5y7ip file: cache/cord-253447-4w6caxwu.json key: cord-253447-4w6caxwu authors: Zeng, Xin; Li, Lingfang; Lin, Jing; Li, Xinlei; Liu, Bin; Kong, Yang; Zeng, Shunze; Du, Jianhua; Xiao, Huahong; Zhang, Tao; Zhang, Shelin; Liu, Jianghai title: Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy date: 2020-04-20 journal: bioRxiv DOI: 10.1101/2020.04.19.049643 sha: doc_id: 253447 cord_uid: 4w6caxwu file: cache/cord-104036-790vk1cf.json key: cord-104036-790vk1cf authors: Liekkinen, Juho; de Santos Moreno, Berta; Paananen, Riku O.; Vattulainen, Ilpo; Monticelli, Luca; de la Serna, Jorge Bernardino; Javanainen, Matti title: Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level date: 2020-07-08 journal: bioRxiv DOI: 10.1101/2020.07.07.191569 sha: doc_id: 104036 cord_uid: 790vk1cf file: cache/cord-252597-ea78sjcs.json key: cord-252597-ea78sjcs authors: Ramazzotti, Daniele; Angaroni, Fabrizio; Maspero, Davide; Gambacorti-Passerini, Carlo; Antoniotti, Marco; Graudenzi, Alex; Piazza, Rocco title: VERSO: a comprehensive framework for the inference of robust phylogenies and the quantification of intra-host genomic diversity of viral samples date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2020.04.22.044404 sha: doc_id: 252597 cord_uid: ea78sjcs file: cache/cord-258630-mvz2l3yj.json key: cord-258630-mvz2l3yj authors: Liu, Tiantian; Chen, Zhong; Chen, Wanqiu; Chen, Xin; Hosseini, Maryam; Yang, Zhaowei; Li, Jing; Ho, Diana; Turay, David; Gheorghe, Ciprian; Jones, Wendell; Wang, Charles title: A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples date: 2020-11-10 journal: bioRxiv DOI: 10.1101/2020.11.10.375022 sha: doc_id: 258630 cord_uid: mvz2l3yj file: cache/cord-255440-ls1l2mlg.json key: cord-255440-ls1l2mlg authors: Tindle, Courtney; Fuller, MacKenzie; Fonseca, Ayden; Taheri, Sahar; Ibeawuchi, Stella-Rita; Beutler, Nathan; Claire, Amanraj; Castillo, Vanessa; Hernandez, Moises; Russo, Hana; Duran, Jason; Crotty Alexander, Laura E.; Tipps, Ann; Lin, Grace; Thistlethwaite, Patricia A.; Chattopadhyay, Ranajoy; Rogers, Thomas F.; Sahoo, Debashis; Ghosh, Pradipta; Das, Soumita title: Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19 date: 2020-10-18 journal: bioRxiv DOI: 10.1101/2020.10.17.344002 sha: doc_id: 255440 cord_uid: ls1l2mlg file: cache/cord-258914-g6pv8zz9.json key: cord-258914-g6pv8zz9 authors: Proud, Pamela C.; Tsitoura, Daphne; Watson, Robert J.; Chua, Brendon Y; Aram, Marilyn J.; Bewley, Kevin R.; Cavell, Breeze E.; Cobb, Rebecca; Dowall, Stuart; Fotheringham, Susan A.; Ho, Catherine M. K.; Lucas, Vanessa; Ngabo, Didier; Rayner, Emma; Ryan, Kathryn A.; Slack, Gillian S.; Thomas, Stephen; Wand, Nadina I.; Yeates, Paul; Demaison, Christophe; Jackson, David C.; Bartlett, Nathan W.; Mercuri, Francesca; Carroll, Miles W. title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date: 2020-09-25 journal: bioRxiv DOI: 10.1101/2020.09.25.309914 sha: doc_id: 258914 cord_uid: g6pv8zz9 file: cache/cord-256607-wpywh8c9.json key: cord-256607-wpywh8c9 authors: Itokawa, Kentaro; Sekizuka, Tsuyoshi; Hashino, Masanori; Tanaka, Rina; Kuroda, Makoto title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR date: 2020-06-01 journal: bioRxiv DOI: 10.1101/2020.03.10.985150 sha: doc_id: 256607 cord_uid: wpywh8c9 file: cache/cord-255552-k1retwa4.json key: cord-255552-k1retwa4 authors: Gassen, Nils C.; Papies, Jan; Bajaj, Thomas; Dethloff, Frederik; Emanuel, Jackson; Weckmann, Katja; Heinz, Daniel E.; Heinemann, Nicolas; Lennarz, Martina; Richter, Anja; Niemeyer, Daniela; Corman, Victor M.; Giavalisco, Patrick; Drosten, Christian; Müller, Marcel A. title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date: 2020-04-15 journal: bioRxiv DOI: 10.1101/2020.04.15.997254 sha: doc_id: 255552 cord_uid: k1retwa4 file: cache/cord-255755-5jccb3nh.json key: cord-255755-5jccb3nh authors: Saha, Sovan; Chatterjee, Piyali; Basu, Subhadip; Nasipuri, Mita title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network date: 2020-04-23 journal: bioRxiv DOI: 10.1101/2020.04.12.038216 sha: doc_id: 255755 cord_uid: 5jccb3nh file: cache/cord-104169-2sbc1guz.json key: cord-104169-2sbc1guz authors: Satish, Swarup; Yao, Zonghai; Drozdov, Andrew; Veytsman, Boris title: The impact of preprint servers in the formation of novel ideas date: 2020-10-08 journal: bioRxiv DOI: 10.1101/2020.10.08.330696 sha: doc_id: 104169 cord_uid: 2sbc1guz file: cache/cord-255325-tl5fm2yu.json key: cord-255325-tl5fm2yu authors: Goletic, Teufik; 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De Luigi, Ada; Violatto, Martina Bruna; Lopez, Gianluca; Gabanti, Elisa; Carsana, Luca; D’Amato, Maura; Morosini, Monica; De Amici, Mara; Nebuloni, Manuela; Fossali, Tommaso; Colombo, Riccardo; Saracino, Laura; Codullo, Veronica; Gnecchi, Massimiliano; Bigini, Paolo; Baldanti, Fausto; Lilleri, Daniele; Meloni, Federica title: Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis date: 2020-11-09 journal: bioRxiv DOI: 10.1101/2020.11.09.374769 sha: doc_id: 254772 cord_uid: 1xzkfl8g file: cache/cord-259246-azt5sr9w.json key: cord-259246-azt5sr9w authors: Peng, Qi; Peng, Ruchao; Yuan, Bin; Wang, Min; Zhao, Jingru; Fu, Lifeng; Qi, Jianxun; Shi, Yi title: Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2020.10.19.345470 sha: doc_id: 259246 cord_uid: azt5sr9w file: cache/cord-255888-znfgh78m.json key: cord-255888-znfgh78m authors: Fisher, Dale; Reilly, Alan; Zheng, Adrian Kang Eng; Cook, Alex R; Anderson, Danielle E. title: Seeding of outbreaks of COVID-19 by contaminated fresh and frozen food date: 2020-08-18 journal: bioRxiv DOI: 10.1101/2020.08.17.255166 sha: doc_id: 255888 cord_uid: znfgh78m file: cache/cord-259261-fmuozy3w.json key: cord-259261-fmuozy3w authors: Bickler, Stephen W.; Cauvi, David M.; Fisch, Kathleen M.; Prieto, James M.; Gaidry, Alicia D.; Thangarajah, Hariharan; Lazar, David; Ignacio, Romeo; Gerstmann, Dale R.; Ryan, Allen F.; Bickler, Philip E.; De Maio, Antonio title: AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.15.134403 sha: doc_id: 259261 cord_uid: fmuozy3w file: cache/cord-260508-z11exbyu.json key: cord-260508-z11exbyu authors: Wang, Hongru; Pipes, Lenore; Nielsen, Rasmus title: Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.04.20.052019 sha: doc_id: 260508 cord_uid: z11exbyu file: cache/cord-255371-o9oxchq6.json key: cord-255371-o9oxchq6 authors: Nguyen, Thanh Thi; Pathirana, Pubudu N.; Nguyen, Thin; Nguyen, Henry; Bhatti, Asim; Nguyen, Dinh C.; Nguyen, Dung Tien; Nguyen, Ngoc Duy; Creighton, Douglas; Abdelrazek, Mohamed title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) date: 2020-07-10 journal: bioRxiv DOI: 10.1101/2020.07.10.171769 sha: doc_id: 255371 cord_uid: o9oxchq6 file: cache/cord-259620-qigfstxt.json key: cord-259620-qigfstxt authors: Yang, Chen; Zhang, Yu; Chen, Hong; Chen, Yuchen; Yang, Dong; Shen, Ziwei; Wang, Xiaomu; Liu, Xinran; Xiong, Mingrui; Huang, Kun title: Kidney injury molecule-1 is a potential receptor for SARS-CoV-2 date: 2020-10-10 journal: bioRxiv DOI: 10.1101/2020.10.09.334052 sha: doc_id: 259620 cord_uid: qigfstxt file: cache/cord-255515-7se14455.json key: cord-255515-7se14455 authors: Graudenzi, Alex; Maspero, Davide; Angaroni, Fabrizio; Piazza, Rocco; Ramazzotti, Daniele title: Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity date: 2020-07-06 journal: bioRxiv DOI: 10.1101/2020.07.06.189944 sha: doc_id: 255515 cord_uid: 7se14455 file: cache/cord-258650-aeyf0yu1.json key: cord-258650-aeyf0yu1 authors: Joshi, Bhrugesh; Bakarola, Vishvajit; Shah, Parth; Krishnamurthy, Ramar title: deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 date: 2020-04-02 journal: bioRxiv DOI: 10.1101/2020.03.30.014555 sha: doc_id: 258650 cord_uid: aeyf0yu1 file: cache/cord-261961-u4d0vvmq.json key: cord-261961-u4d0vvmq authors: St-Germain, Jonathan R.; Astori, Audrey; Samavarchi-Tehrani, Payman; Abdouni, Hala; Macwan, Vinitha; Kim, Dae-Kyum; Knapp, Jennifer J.; Roth, Frederick P.; Gingras, Anne-Claude; Raught, Brian title: A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.08.28.269175 sha: doc_id: 261961 cord_uid: u4d0vvmq file: cache/cord-255895-6at9gelt.json key: cord-255895-6at9gelt authors: Han, Namshik; Hwang, Woochang; Tzelepis, Konstantinos; Schmerer, Patrick; Yankova, Eliza; MacMahon, Méabh; Lei, Winnie; Katritsis, Nicholas M; Liu, Anika; Schuldt, Alison; Harris, Rebecca; Chapman, Kathryn; McCaughan, Frank; Weber, Friedemann; Kouzarides, Tony title: Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies date: 2020-08-25 journal: bioRxiv DOI: 10.1101/2020.08.24.265496 sha: doc_id: 255895 cord_uid: 6at9gelt file: cache/cord-260054-iihgc5nr.json key: cord-260054-iihgc5nr authors: Cavallo, Luigi; Oliva, Romina title: D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly date: 2020-06-08 journal: bioRxiv DOI: 10.1101/2020.06.08.140152 sha: doc_id: 260054 cord_uid: iihgc5nr file: cache/cord-262145-i29e3fge.json key: cord-262145-i29e3fge authors: Huang, Kuan-Ying A.; Tan, Tiong Kit; Chen, Ting-Hua; Huang, Chung-Guei; Harvey, Ruth; Hussain, Saira; Chen, Cheng-Pin; Harding, Adam; Gilbert-Jaramillo, Javier; Liu, Xu; Knight, Michael; Schimanski, Lisa; Shih, Shin-Ru; Lin, Yi-Chun; Cheng, Chien-Yu; Cheng, Shu-Hsing; Huang, Yhu-Chering; Lin, Tzou-Yien; Jan, Jia-Tsrong; Ma, Che; James, William; Daniels, Rodney S.; McCauley, John W.; Rijal, Pramila; Townsend, Alain R. title: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2020.08.28.267526 sha: doc_id: 262145 cord_uid: i29e3fge file: cache/cord-255791-ghrlj6b2.json key: cord-255791-ghrlj6b2 authors: Pruijssers, Andrea J.; George, Amelia S.; Schäfer, Alexandra; Leist, Sarah R.; Gralinksi, Lisa E.; Dinnon, Kenneth H.; Yount, Boyd L.; Agostini, Maria L.; Stevens, Laura J.; Chappell, James D.; Lu, Xiaotao; Hughes, Tia M.; Gully, Kendra; Martinez, David R.; Brown, Ariane J.; Graham, Rachel L.; Perry, Jason K.; Du Pont, Venice; Pitts, Jared; Ma, Bin; Babusis, Darius; Murakami, Eisuke; Feng, Joy Y.; Bilello, John P.; Porter, Danielle P.; Cihlar, Tomas; Baric, Ralph S.; Denison, Mark R.; Sheahan, Timothy P. title: Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice date: 2020-04-27 journal: bioRxiv DOI: 10.1101/2020.04.27.064279 sha: doc_id: 255791 cord_uid: ghrlj6b2 file: cache/cord-259340-1ir19s25.json key: cord-259340-1ir19s25 authors: Das, Rohit Pritam; Jagadeb, Manaswini; Rath, Surya Narayan title: Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.07.01.150805 sha: doc_id: 259340 cord_uid: 1ir19s25 file: cache/cord-262602-on0w55x0.json key: cord-262602-on0w55x0 authors: Muruato, Antonio E.; Fontes-Garfias, Camila R.; Ren, Ping; Garcia-Blanco, Mariano A.; Menachery, Vineet D.; Xie, Xuping; Shi, Pei-Yong title: A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.21.109546 sha: doc_id: 262602 cord_uid: on0w55x0 file: cache/cord-260352-rhd0qqyn.json key: cord-260352-rhd0qqyn authors: Bhattacharyya, Sumit; Kotlo, Kumar; Tobacman, Joanne K. title: Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity date: 2020-06-25 journal: bioRxiv DOI: 10.1101/2020.06.25.171975 sha: doc_id: 260352 cord_uid: rhd0qqyn file: cache/cord-258360-fqrn02lr.json key: cord-258360-fqrn02lr authors: Lee, Jimmy; Hughes, Tom; Lee, Mei-Ho; Field, Hume; Rovie-Ryan, Jeffrine Japning; Sitam, Frankie Thomas; Sipangkui, Symphorosa; Nathan, Senthilvel K.S.S.; Ramirez, Diana; Kumar, Subbiah Vijay; Lasimbang, Helen; Epstein, Jonathan H.; Daszak, Peter title: No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.19.158717 sha: doc_id: 258360 cord_uid: fqrn02lr file: cache/cord-261435-wcn4bjnw.json key: cord-261435-wcn4bjnw authors: Ren, Xianwen; Wen, Wen; Fan, Xiaoying; Hou, Wenhong; Su, Bin; Cai, Pengfei; Li, Jiesheng; Liu, Yang; Tang, Fei; Zhang, Fan; Yang, Yu; He, Jiangping; Ma, Wenji; He, Jingjing; Wang, Pingping; Cao, Qiqi; Chen, Fangjin; Chen, Yuqing; Cheng, Xuelian; Deng, Guohong; Deng, Xilong; Ding, Wenyu; Feng, Yingmei; Gan, Rui; Guo, Chuang; Guo, Weiqiang; He, Shuai; Jiang, Chen; Liang, Juanran; Li, Yi-min; Lin, Jun; Ling, Yun; Liu, Haofei; Liu, Jianwei; Liu, Nianping; Liu, Yang; Luo, Meng; Ma, Qiang; Song, Qibing; Sun, Wujianan; Wang, GaoXiang; Wang, Feng; Wang, Ying; Wen, Xiaofeng; Wu, Qian; Xu, Gang; Xie, Xiaowei; Xiong, Xinxin; Xing, Xudong; Xu, Hao; Yin, Chonghai; Yu, Dongdong; Yu, Kezhuo; Yuan, Jin; Zhang, Biao; Zhang, Tong; Zhao, Jincun; Zhao, Peidong; Zhou, Jianfeng; Zhou, Wei; Zhong, Sujuan; Zhong, Xiaosong; Zhang, Shuye; Zhu, Lin; Zhu, Ping; Zou, Bin; Zou, Jiahua; Zuo, Zengtao; Bai, Fan; Huang, Xi; Bian, Xiuwu; Zhou, Penghui; Jiang, Qinghua; Huang, Zhiwei; Bei, Jin-Xin; Wei, Lai; Liu, Xindong; Cheng, Tao; Li, Xiangpan; Zhao, Pingsen; Wang, Fu-Sheng; Wang, Hongyang; Su, Bing; Zhang, Zheng; Qu, Kun; Wang, Xiaoqun; Chen, Jiekai; Jin, Ronghua; Zhang, Zemin title: Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients date: 2020-10-29 journal: bioRxiv DOI: 10.1101/2020.10.29.360479 sha: doc_id: 261435 cord_uid: wcn4bjnw file: cache/cord-256572-sqz8yc7b.json key: cord-256572-sqz8yc7b authors: Huo, Jiandong; Zhao, Yuguang; Ren, Jingshan; Zhou, Daming; Duyvesteyn, Helen ME; Ginn, Helen M; Carrique, Loic; Malinauskas, Tomas; Ruza, Reinis R; Shah, Pranav NM; Tan, Tiong Kit; Rijal, Pramila; Coombes, Naomi; Bewley, Kevin; Radecke, Julika; Paterson, Neil G; Supasa, Piyasa; Mongkolsapaya, Juthathip; Screaton, Gavin R; Carroll, Miles; Townsend, Alain; Fry, Elizabeth E; Owens, Raymond J; Stuart, David I title: Neutralization of SARS-CoV-2 by destruction of the prefusion Spike date: 2020-05-06 journal: bioRxiv DOI: 10.1101/2020.05.05.079202 sha: doc_id: 256572 cord_uid: sqz8yc7b file: cache/cord-261718-zqoggwnk.json key: cord-261718-zqoggwnk authors: Pietschmann, Jan; Vöpel, Nadja; Spiegel, Holger; Krause, Hans-Joachim; Schröper, Florian title: Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date: 2020-06-03 journal: bioRxiv DOI: 10.1101/2020.06.02.131102 sha: doc_id: 261718 cord_uid: zqoggwnk file: cache/cord-260793-bb4h255w.json key: cord-260793-bb4h255w authors: Brann, David H.; Tsukahara, Tatsuya; Weinreb, Caleb; Lipovsek, Marcela; Van den Berge, Koen; Gong, Boying; Chance, Rebecca; Macaulay, Iain C.; Chou, Hsin-jung; Fletcher, Russell; Das, Diya; Street, Kelly; de Bezieux, Hector Roux; Choi, Yoon-Gi; Risso, Davide; Dudoit, Sandrine; Purdom, Elizabeth; Mill, Jonathan S.; Hachem, Ralph Abi; Matsunami, Hiroaki; Logan, Darren W.; Goldstein, Bradley J.; Grubb, Matthew S.; Ngai, John; Datta, Sandeep Robert title: Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia date: 2020-05-18 journal: bioRxiv DOI: 10.1101/2020.03.25.009084 sha: doc_id: 260793 cord_uid: bb4h255w file: cache/cord-262958-tmp6yxlv.json key: cord-262958-tmp6yxlv authors: Pinto, Dora; Park, Young-Jun; Beltramello, Martina; Walls, Alexandra C.; Tortorici, M. Alejandra; Bianchi, Siro; Jaconi, Stefano; Culap, Katja; Zatta, Fabrizia; De Marco, Anna; Peter, Alessia; Guarino, Barbara; Spreafico, Roberto; Cameroni, Elisabetta; Case, James Brett; Chen, Rita E.; Havenar-Daughton, Colin; Snell, Gyorgy; Telenti, Amalio; Virgin, Herbert W.; Lanzavecchia, Antonio; Diamond, Michael S.; Fink, Katja; Veesler, David; Corti, Davide title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody date: 2020-04-09 journal: bioRxiv DOI: 10.1101/2020.04.07.023903 sha: doc_id: 262958 cord_uid: tmp6yxlv file: cache/cord-260481-twk5kvd3.json key: cord-260481-twk5kvd3 authors: Täufer, Matthias title: Rapid, large-scale, and effective detection of COVID-19 via non-adaptive testing date: 2020-08-18 journal: bioRxiv DOI: 10.1101/2020.04.06.028431 sha: doc_id: 260481 cord_uid: twk5kvd3 file: cache/cord-261688-njlxrxv6.json key: cord-261688-njlxrxv6 authors: Yang, Ziwei; Zhang, Xiaolin; Wang, Fan; Wang, Peihui; Kuang, Ersheng; Li, Xiaojuan title: Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2 date: 2020-08-12 journal: bioRxiv DOI: 10.1101/2020.08.12.247767 sha: doc_id: 261688 cord_uid: njlxrxv6 file: cache/cord-262726-lfuxhlki.json key: cord-262726-lfuxhlki authors: Diallo, Aïssatou Bailo; Gay, Laetitia; Coiffard, Benjamin; Leone, Marc; Mezouar, Soraya; Mege, Jean-Louis title: Daytime variation in SARS-CoV-2 infection and cytokine production date: 2020-09-11 journal: bioRxiv DOI: 10.1101/2020.09.09.290718 sha: doc_id: 262726 cord_uid: lfuxhlki file: cache/cord-255997-oer5lxxr.json key: cord-255997-oer5lxxr authors: Onodi, Fanny; Bonnet-Madin, Lucie; Karpf, Léa; Meertens, Laurent; Poirot, Justine; Legoff, Jérome; Delaugerre, Constance; Amara, Ali; Soumelis, Vassili title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 journal: bioRxiv DOI: 10.1101/2020.07.10.197343 sha: doc_id: 255997 cord_uid: oer5lxxr file: cache/cord-260315-uau554jj.json key: cord-260315-uau554jj authors: Ramirez, Santseharay; Fernandez-Antunez, Carlota; Pham, Long V.; Ryberg, Line A.; Feng, Shan; Pedersen, Martin S.; Mikkelsen, Lotte S.; Belouzard, Sandrine; Dubuisson, Jean; Gottwein, Judith M.; Fahnøe, Ulrik; Bukh, Jens title: Efficient culture of SARS-CoV-2 in human hepatoma cells enhances viability of the virus in human lung cancer cell lines permitting the screening of antiviral compounds date: 2020-10-04 journal: bioRxiv DOI: 10.1101/2020.10.04.325316 sha: doc_id: 260315 cord_uid: uau554jj file: cache/cord-261662-d0tg9i90.json key: cord-261662-d0tg9i90 authors: Andres, Cristina; Garcia-Cehic, Damir; Gregori, Josep; Piñana, Maria; Rodriguez-Frias, Francisco; Guerrero-Murillo, Mercedes; Esperalba, Juliana; Rando, Ariadna; Goterris, Lidia; Codina, Maria Gema; Quer, Susanna; Martín, Maria Carmen; Campins, Magda; Ferrer, Ricard; Almirante, Benito; Esteban, Juan Ignacio; Pumarola, Tomás; Antón, Andrés; Quer, Josep title: Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients date: 2020-06-08 journal: bioRxiv DOI: 10.1101/2020.06.03.129585 sha: doc_id: 261662 cord_uid: d0tg9i90 file: cache/cord-259084-lwh3rww4.json key: cord-259084-lwh3rww4 authors: Anderson, Cole; Castillo, Fritz; Koenig, Michael; Managbanag, Jim title: Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2 date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.22.110932 sha: doc_id: 259084 cord_uid: lwh3rww4 file: cache/cord-262573-wdgbno9p.json key: cord-262573-wdgbno9p authors: Begum, Feroza; Mukherjee, Debica; Thagriki, Dluya; Das, Sandeepan; Tripathi, Prem Prakash; Banerjee, Arup Kumar; Ray, Upasana title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India date: 2020-05-03 journal: bioRxiv DOI: 10.1101/2020.04.28.066985 sha: doc_id: 262573 cord_uid: wdgbno9p file: cache/cord-264012-q2quyijg.json key: cord-264012-q2quyijg authors: Lim, Su Bin; Dawson, Valina L.; Dawson, Ted M.; Kang, Sung-Ung title: ACE2-expressing endothelial cells in aging mouse brain date: 2020-07-11 journal: bioRxiv DOI: 10.1101/2020.07.11.198770 sha: doc_id: 264012 cord_uid: q2quyijg file: cache/cord-263008-w6twrjzr.json key: cord-263008-w6twrjzr authors: Yin, Rui; Luo, Zihan; Kwoh, Chee Keong title: Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide date: 2020-07-15 journal: bioRxiv DOI: 10.1101/2020.07.15.176933 sha: doc_id: 263008 cord_uid: w6twrjzr file: cache/cord-262485-sx2q5ol4.json key: cord-262485-sx2q5ol4 authors: Davda, Jayeshkumar Narsibhai; Frank, Keith; Prakash, Sivakumar; Purohit, Gunjan; Vijayashankar, Devi Prasad; Vedagiri, Dhiviya; Tallapaka, Karthik Bharadwaj; Harshan, Krishnan Harinivas; Siva, Archana Bharadwaj; Mishra, Rakesh Kumar; Dhawan, Jyotsna; Siddiqi, Imran title: An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance date: 2020-06-08 journal: bioRxiv DOI: 10.1101/2020.06.08.139477 sha: doc_id: 262485 cord_uid: sx2q5ol4 file: cache/cord-263594-jd9ako6c.json key: cord-263594-jd9ako6c authors: Kang, Sisi; Yang, Mei; He, Suhua; Wang, Yueming; Chen, Xiaoxue; Chen, Yao-Qing; Hong, Zhongsi; Liu, Jing; Jiang, Guanmin; Chen, Qiuyue; Zhou, Ziliang; Zhou, Zhechong; Huang, Zhaoxia; Huang, Xi; He, Huanhuan; Zheng, Weihong; Liao, Hua-Xin; Xiao, Fei; Shan, Hong; Chen, Shoudeng title: A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation date: 2020-09-11 journal: bioRxiv DOI: 10.1101/2020.09.10.292318 sha: doc_id: 263594 cord_uid: jd9ako6c file: cache/cord-262470-nkql7h9x.json key: cord-262470-nkql7h9x authors: Muus, Christoph; Luecken, Malte D.; Eraslan, Gokcen; Waghray, Avinash; Heimberg, Graham; Sikkema, Lisa; Kobayashi, Yoshihiko; Vaishnav, Eeshit Dhaval; Subramanian, Ayshwarya; Smilie, Christopher; Jagadeesh, Karthik; Duong, Elizabeth Thu; Fiskin, Evgenij; Triglia, Elena Torlai; Ansari, Meshal; Cai, Peiwen; Lin, Brian; Buchanan, Justin; Chen, Sijia; Shu, Jian; Haber, Adam L; Chung, Hattie; Montoro, Daniel T; Adams, Taylor; Aliee, Hananeh; Samuel, J.; Andrusivova, Allon Zaneta; Angelidis, Ilias; Ashenberg, Orr; Bassler, Kevin; Bécavin, Christophe; Benhar, Inbal; Bergenstråhle, Joseph; Bergenstråhle, Ludvig; Bolt, Liam; Braun, Emelie; Bui, Linh T; Chaffin, Mark; Chichelnitskiy, Evgeny; Chiou, Joshua; Conlon, Thomas M; Cuoco, Michael S; Deprez, Marie; Fischer, David S; Gillich, Astrid; Gould, Joshua; Guo, Minzhe; Gutierrez, Austin J; Habermann, Arun C; Harvey, Tyler; He, Peng; Hou, Xiaomeng; Hu, Lijuan; Jaiswal, Alok; Jiang, Peiyong; Kapellos, Theodoros; Kuo, Christin S; Larsson, Ludvig; Kyungtae Lim, Michael A. Leney-Greene; Litviňuková, Monika; Lu, Ji; Maatz, Henrike; Madissoon, Elo; Mamanova, Lira; Manakongtreecheep, Kasidet; Marquette, Charles-Hugo; Mbano, Ian; McAdams, Alexi Marie; Metzger, Ross J; Nabhan, Ahmad N; Nyquist, Sarah K.; Ordovas-Montanes, Jose; Penland, Lolita; Poirion, Olivier B; Poli, Sergio; Qi, CanCan; Reichart, Daniel; Rosas, Ivan; Schupp, Jonas; Sinha, Rahul; Sit, Rene V; Slowikowski, Kamil; Slyper, Michal; Smith, Neal; Sountoulidis, Alex; Strunz, Maximilian; Sun, Dawei; Talavera-López, Carlos; Tan, Peng; Tantivit, Jessica; Travaglini, Kyle J; Tucker, Nathan R.; Vernon, Katherine; Wadsworth, Marc H.; Waldmann, Julia; Wang, Xiuting; Yan, Wenjun; Zhao, William; Ziegler, Carly G. K. title: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells date: 2020-04-20 journal: bioRxiv DOI: 10.1101/2020.04.19.049254 sha: doc_id: 262470 cord_uid: nkql7h9x file: cache/cord-262119-s6hc7fxs.json key: cord-262119-s6hc7fxs authors: Ostaszewski, Marek; Niarakis, Anna; Mazein, Alexander; Kuperstein, Inna; Phair, Robert; Orta-Resendiz, Aurelio; Singh, Vidisha; Aghamiri, Sara Sadat; Acencio, Marcio Luis; Glaab, Enrico; Ruepp, Andreas; Fobo, Gisela; Montrone, Corinna; Brauner, Barbara; Frischman, Goar; Monraz Gómez, Luis Cristóbal; Somers, Julia; Hoch, Matti; Gupta, Shailendra Kumar; Scheel, Julia; Borlinghaus, Hanna; Czauderna, Tobias; Schreiber, Falk; Montagud, Arnau; de Leon, Miguel Ponce; Funahashi, Akira; Hiki, Yusuke; Hiroi, Noriko; Yamada, Takahiro G.; Dräger, Andreas; Renz, Alina; Naveez, Muhammad; Bocskei, Zsolt; Messina, Francesco; Börnigen, Daniela; Fergusson, Liam; Conti, Marta; Rameil, Marius; Nakonecnij, Vanessa; Vanhoefer, Jakob; Schmiester, Leonard; Wang, Muying; Ackerman, Emily E.; Shoemaker, Jason; Zucker, Jeremy; Oxford, Kristie; Teuton, Jeremy; Kocakaya, Ebru; Summak, Gökçe Yağmur; Hanspers, Kristina; Kutmon, Martina; Coort, Susan; Eijssen, Lars; Ehrhart, Friederike; Rex, D. A. B.; Slenter, Denise; Martens, Marvin; Haw, Robin; Jassal, Bijay; Matthews, Lisa; Orlic-Milacic, Marija; Senff Ribeiro, Andrea; Rothfels, Karen; Shamovsky, Veronica; Stephan, Ralf; Sevilla, Cristoffer; Varusai, Thawfeek; Ravel, Jean-Marie; Fraser, Rupsha; Ortseifen, Vera; Marchesi, Silvia; Gawron, Piotr; Smula, Ewa; Heirendt, Laurent; Satagopam, Venkata; Wu, Guanming; Riutta, Anders; Golebiewski, Martin; Owen, Stuart; Goble, Carole; Hu, Xiaoming; Overall, Rupert W.; Maier, Dieter; Bauch, Angela; Gyori, Benjamin M.; Bachman, John A.; Vega, Carlos; Grouès, Valentin; Vazquez, Miguel; Porras, Pablo; Licata, Luana; Iannuccelli, Marta; Sacco, Francesca; Nesterova, Anastasia; Yuryev, Anton; de Waard, Anita; Turei, Denes; Luna, Augustin; Babur, Ozgun; Soliman, Sylvain; Valdeolivas, Alberto; Esteban-Medina, Marina; Peña-Chilet, Maria; Helikar, Tomáš; Puniya, Bhanwar Lal; Modos, Dezso; Treveil, Agatha; Olbei, Marton; De Meulder, Bertrand; Dugourd, Aurélien; Naldi, Aurelien; Noel, Vincent; Calzone, Laurence; Sander, Chris; Demir, Emek; Korcsmaros, Tamas; Freeman, Tom C.; Augé, Franck; Beckmann, Jacques S.; Hasenauer, Jan; Wolkenhauer, Olaf; Wilighagen, Egon L.; Pico, Alexander R.; Evelo, Chris T.; Gillespie, Marc E.; Stein, Lincoln D.; Hermjakob, Henning; D’Eustachio, Peter; Saez-Rodriguez, Julio; Dopazo, Joaquin; Valencia, Alfonso; Kitano, Hiroaki; Barillot, Emmanuel; Auffray, Charles; Balling, Rudi; Schneider, Reinhard title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 journal: bioRxiv DOI: 10.1101/2020.10.26.356014 sha: doc_id: 262119 cord_uid: s6hc7fxs file: cache/cord-264031-0y7xbgun.json key: cord-264031-0y7xbgun authors: Wierbowski, Shayne D.; Liang, Siqi; Chen, You; Andre, Nicole M.; Lipkin, Steven M.; Whittaker, Gary R.; Yu, Haiyuan title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 journal: bioRxiv DOI: 10.1101/2020.10.13.308676 sha: doc_id: 264031 cord_uid: 0y7xbgun file: cache/cord-261855-qpbgq5d8.json key: cord-261855-qpbgq5d8 authors: Walker, Susanne N.; Chokkalingam, Neethu; Reuschel, Emma L.; Purwar, Mansi; Xu, Ziyang; Gary, Ebony N.; Kim, Kevin Y.; Schultheis, Katherine; Walters, Jewell; Ramos, Stephanie; Smith, Trevor R.F.; Broderick, Kate E.; Tebas, Pablo; Patel, Ami; Weiner, David B.; Kulp, Daniel W. title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients date: 2020-06-18 journal: bioRxiv DOI: 10.1101/2020.06.17.158527 sha: doc_id: 261855 cord_uid: qpbgq5d8 file: cache/cord-267115-6jqdi417.json key: cord-267115-6jqdi417 authors: Giobbe, Giovanni Giuseppe; Bonfante, Francesco; Zambaiti, Elisa; Gagliano, Onelia; Jones, Brendan C.; Luni, Camilla; Laterza, Cecilia; Perin, Silvia; Stuart, Hannah T.; Pagliari, Matteo; Bortolami, Alessio; Mazzetto, Eva; Manfredi, Anna; Colantuono, Chiara; Di Filippo, Lucio; Pellegata, Alessandro; Li, Vivian Sze Wing; Eaton, Simon; Thapar, Nikhil; Cacchiarelli, Davide; Elvassore, Nicola; De Coppi, Paolo title: SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.06.24.167049 sha: doc_id: 267115 cord_uid: 6jqdi417 file: cache/cord-265453-z6aux01t.json key: cord-265453-z6aux01t authors: Bierig, Tobias; Collu, Gabriella; Blanc, Alain; Poghosyan, Emiliya; Benoit, Roger. M. title: Design, expression, purification and characterization of a YFP-tagged 2019-nCoV spike receptor-binding domain construct date: 2020-09-29 journal: bioRxiv DOI: 10.1101/2020.09.29.318196 sha: doc_id: 265453 cord_uid: z6aux01t file: cache/cord-265418-yqe9vdj1.json key: cord-265418-yqe9vdj1 authors: Kumar, Nilesh; Mishra, Bharat; Mehmood, Adeel; Athar, Mohammad; Mukhtar, M. Shahid title: Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.09.033910 sha: doc_id: 265418 cord_uid: yqe9vdj1 file: cache/cord-263780-8jejswuk.json key: cord-263780-8jejswuk authors: Wang, Nan; Han, Shengli; Liu, Rui; Meng, Liesu; He, Huaizhen; Zhang, Yongjing; Wang, Cheng; Lv, Yanni; Wang, Jue; Li, Xiaowei; Ding, Yuanyuan; Fu, Jia; Hou, Yajing; Lu, Wen; Ma, Weina; Zhan, Yingzhuan; Dai, Bingling; Zhang, Jie; Pan, Xiaoyan; Hu, Shiling; Gao, Jiapan; Jia, Qianqian; Zhang, Liyang; Ge, Shuai; Wang, Saisai; Liang, Peida; Hu, Tian; Lu, Jiayu; Wang, Xiangjun; Zhou, Huaxin; Ta, Wenjing; Wang, Yuejin; Lu, Shemin; He, Langchong title: Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.06.22.164665 sha: doc_id: 263780 cord_uid: 8jejswuk file: cache/cord-264204-4ablrwuo.json key: cord-264204-4ablrwuo authors: Guintivano, Jerry; Dick, Danielle; Bulik, Cynthia M title: Psychiatric Genomics Research During the COVID-19 Pandemic: A Survey of Psychiatric Genomics Consortium Researchers date: 2020-10-08 journal: bioRxiv DOI: 10.1101/2020.10.08.331421 sha: doc_id: 264204 cord_uid: 4ablrwuo file: cache/cord-267223-pf799wbw.json key: cord-267223-pf799wbw authors: de Lamballerie, Claire Nicolas; Pizzorno, Andrés; Fouret, Julien; Szpiro, Lea; Padey, Blandine; Dubois, Julia; Julien, Thomas; Traversier, Aurélien; Dulière, Victoria; Brun, Pauline; Lina, Bruno; Rosa-Calatrava, Manuel; Terrier, Olivier title: Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection in a human airway epithelial model date: 2020-05-19 journal: bioRxiv DOI: 10.1101/2020.05.19.103630 sha: doc_id: 267223 cord_uid: pf799wbw file: cache/cord-263970-9w6ciglv.json key: cord-263970-9w6ciglv authors: Marquez-Miranda, Valeria; Rojas, Maximiliano; Duarte, Yorley; Diaz-Franulic, Ignacio; Holmgren, Miguel; Cachau, Raul E.; Gonzalez-Nilo, Fernando D. title: Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites date: 2020-10-22 journal: bioRxiv DOI: 10.1101/2020.10.22.349522 sha: doc_id: 263970 cord_uid: 9w6ciglv file: cache/cord-267613-hsc2x36j.json key: cord-267613-hsc2x36j authors: Dittmar, Mark; Lee, Jae Seung; Whig, Kanupriya; Segrist, Elisha; Li, Minghua; Jurado, Kellie; Samby, Kirandeep; Ramage, Holly; Schultz, David; Cherry, Sara title: Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2 date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.19.161042 sha: doc_id: 267613 cord_uid: hsc2x36j file: cache/cord-269285-2r40mico.json key: cord-269285-2r40mico authors: Resnick, Samuel J.; Iketani, Sho; Hong, Seo Jung; Zask, Arie; Liu, Hengrui; Kim, Sungsoo; Melore, Schuyler; Nair, Manoj S.; Huang, Yaoxing; Tay, Nicholas E.S.; Rovis, Tomislav; Yang, Hee Won; Stockwell, Brent R.; Ho, David D.; Chavez, Alejandro title: A simplified cell-based assay to identify coronavirus 3CL protease inhibitors date: 2020-08-29 journal: bioRxiv DOI: 10.1101/2020.08.29.272864 sha: doc_id: 269285 cord_uid: 2r40mico file: cache/cord-266444-rw94yls8.json key: cord-266444-rw94yls8 authors: Dominguez Andres, Ana; Feng, Yongmei; Campos, Alexandre Rosa; Yin, Jun; Yang, Chih-Cheng; James, Brian; Murad, Rabi; Kim, Hyungsoo; Deshpande, Aniruddha J.; Gordon, David E.; Krogan, Nevan; Pippa, Raffaella; Ronai, Ze’ev A. title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 journal: bioRxiv DOI: 10.1101/2020.08.18.256776 sha: doc_id: 266444 cord_uid: rw94yls8 file: cache/cord-266869-fs8dn7ir.json key: cord-266869-fs8dn7ir authors: Kim, So Young; Jin, Weihua; Sood, Amika; Montgomery, David W.; Grant, Oliver C.; Fuster, Mark M.; Fu, Li; Dordick, Jonathan S.; Woods, Robert J.; Zhang, Fuming; Linhardt, Robert J. title: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry date: 2020-04-15 journal: bioRxiv DOI: 10.1101/2020.04.14.041459 sha: doc_id: 266869 cord_uid: fs8dn7ir file: cache/cord-267482-afqfymbq.json key: cord-267482-afqfymbq authors: Ryu, Seungjin; Shchukina, Irina; Youm, Yun-Hee; Qing, Hua; Hilliard, Brandon K.; Dlugos, Tamara; Zhang, Xinbo; Yasumoto, Yuki; Booth, Carmen J.; Fernández-Hernando, Carlos; Suárez, Yajaira; Khanna, Kamal M.; Horvath, Tamas L.; Dietrich, Marcelo O.; Artyomov, Maxim N.; Wang, Andrew; Dixit, Vishwa Deep title: Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model date: 2020-09-12 journal: bioRxiv DOI: 10.1101/2020.09.11.294363 sha: doc_id: 267482 cord_uid: afqfymbq file: cache/cord-264296-0x90yubt.json key: cord-264296-0x90yubt authors: Sawmya, Shashata; Saha, Arpita; Tasnim, Sadia; Anjum, Naser; Toufikuzzaman, Md.; Rafid, Ali Haisam Muhammad; Rahman, Mohammad Saifur; Rahman, M. Sohel title: Analyzing hCov genome sequences: Applying Machine Intelligence and beyond date: 2020-06-03 journal: bioRxiv DOI: 10.1101/2020.06.03.131987 sha: doc_id: 264296 cord_uid: 0x90yubt file: cache/cord-267536-rvhwl4ea.json key: cord-267536-rvhwl4ea authors: Miyashita, L; Foley, G; Semple, S; Grigg, J title: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells date: 2020-05-27 journal: bioRxiv DOI: 10.1101/2020.05.15.097501 sha: doc_id: 267536 cord_uid: rvhwl4ea file: cache/cord-263090-29n9tsk9.json key: cord-263090-29n9tsk9 authors: Roy, Susmita title: Dynamical asymmetry exposes 2019-nCoV prefusion spike date: 2020-04-21 journal: bioRxiv DOI: 10.1101/2020.04.20.052290 sha: doc_id: 263090 cord_uid: 29n9tsk9 file: cache/cord-265277-ymvrserl.json key: cord-265277-ymvrserl authors: Crooke, Stephen N.; Ovsyannikova, Inna G.; Kennedy, Richard B.; Poland, Gregory A. title: Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome date: 2020-05-14 journal: bioRxiv DOI: 10.1101/2020.05.14.093757 sha: doc_id: 265277 cord_uid: ymvrserl file: cache/cord-263825-g8p2lsr0.json key: cord-263825-g8p2lsr0 authors: Maldonado, Lucas L.; Kamenetzky, Laura title: Molecular features similarities between SARS-CoV-2, SARS, MERS and key human genes could favour the viral infections and trigger collateral effects date: 2020-06-25 journal: bioRxiv DOI: 10.1101/2020.06.23.167072 sha: doc_id: 263825 cord_uid: g8p2lsr0 file: cache/cord-268894-amfv3z2y.json key: cord-268894-amfv3z2y authors: Nguyen-Contant, Phuong; Embong, A. Karim; Kanagaiah, Preshetha; Chaves, Francisco A.; Yang, Hongmei; Branche, Angela R.; Topham, David J.; Sangster, Mark Y. title: S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit date: 2020-07-21 journal: bioRxiv DOI: 10.1101/2020.07.20.213298 sha: doc_id: 268894 cord_uid: amfv3z2y file: cache/cord-267845-18hb5ndr.json key: cord-267845-18hb5ndr authors: Resende, Paola Cristina; Motta, Fernando Couto; Roy, Sunando; Appolinario, Luciana; Fabri, Allison; Xavier, Joilson; Harris, Kathryn; Matos, Aline Rocha; Caetano, Braulia; Orgeswalska, Maria; Miranda, Milene; Garcia, Cristiana; Abreu, André; Williams, Rachel; Breuer, Judith; Siqueira, Marilda M title: SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.04.30.069039 sha: doc_id: 267845 cord_uid: 18hb5ndr file: cache/cord-268224-5tbb8df1.json key: cord-268224-5tbb8df1 authors: Di Gioacchino, Andrea; Šulc, Petr; Komarova, Anastassia V.; Greenbaum, Benjamin D.; Monasson, Rémi; Cocco, Simona title: The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 date: 2020-08-27 journal: bioRxiv DOI: 10.1101/2020.05.06.074039 sha: doc_id: 268224 cord_uid: 5tbb8df1 file: cache/cord-264051-ps0x2es1.json key: cord-264051-ps0x2es1 authors: Li, Wei; Yang, Shuai; Xu, Peng; Zhang, Dapeng; Tong, Ying; Chen, Lu; Jia, Ben; Li, Ang; Ru, Daoping; Zhang, Baolong; Liu, Mengxing; Lian, Cheng; Chen, Cancan; Fu, Weihui; Yuan, Songhua; Ren, Xiaoguang; Liang, Ying; Yang, Zhicong; Li, Wenxuan; Wang, Shaoxuan; Zhang, Xiaoyan; Lu, Hongzhou; Xu, Jianqing; Wang, Hailing; Yu, Wenqiang title: Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.04.361576 sha: doc_id: 264051 cord_uid: ps0x2es1 file: cache/cord-264919-0jlg2gkc.json key: cord-264919-0jlg2gkc authors: Hopp, Marie-Thérèse; Domingo-Fernández, Daniel; Gadiya, Yojana; Detzel, Milena S.; Schmalohr, Benjamin F.; Steinbock, Francèl; Imhof, Diana; Hofmann-Apitius, Martin title: Unravelling the debate on heme effects in COVID-19 infections date: 2020-06-12 journal: bioRxiv DOI: 10.1101/2020.06.09.142125 sha: doc_id: 264919 cord_uid: 0jlg2gkc file: cache/cord-268795-tjmx6msm.json key: cord-268795-tjmx6msm authors: Sardar, Rahila; Satish, Deepshikha; Birla, Shweta; Gupta, Dinesh title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis date: 2020-03-21 journal: bioRxiv DOI: 10.1101/2020.03.21.001586 sha: doc_id: 268795 cord_uid: tjmx6msm file: cache/cord-270049-54t3w94z.json key: cord-270049-54t3w94z authors: Campione, Elena; Lanna, Caterina; Cosio, Terenzio; Rosa, Luigi; Conte, Maria Pia; Iacovelli, Federico; Romeo, Alice; Falconi, Mattia; Del Vecchio, Claudia; Franchin, Elisa; Lia, Maria Stella; Minieri, Marilena; Chiaramonte, Carlo; Ciotti, Marco; Nuccetelli, Marzia; Terrinoni, Alessandro; Iannuzzi, Ilaria; Coppeda, Luca; Magrini, Andrea; Moricca, Nicola; Sabatini, Stefano; Rosapepe, Felice; Bartoletti, Pier Luigi; Bernardini, Sergio; Andreoni, Massimo; Valenti, Piera; Bianchi, Luca title: Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidences date: 2020-08-17 journal: bioRxiv DOI: 10.1101/2020.08.11.244996 sha: doc_id: 270049 cord_uid: 54t3w94z file: cache/cord-268339-jxm69ndw.json key: cord-268339-jxm69ndw authors: Karamitros, Timokratis; Papadopoulou, Gethsimani; Bousali, Maria; Mexias, Anastasios; Tsiodras, Sotiris; Mentis, Andreas title: SARS-CoV-2 exhibits intra-host genomic plasticity and low-frequency polymorphic quasispecies date: 2020-03-28 journal: bioRxiv DOI: 10.1101/2020.03.27.009480 sha: doc_id: 268339 cord_uid: jxm69ndw file: cache/cord-270550-if748w2n.json key: cord-270550-if748w2n authors: Bailey, Adam L.; Dmytrenko, Oleksandr; Greenberg, Lina; Bredemeyer, Andrea L.; Ma, Pan; Liu, Jing; Penna, Vinay; Lai, Lulu; Winkler, Emma S.; Sviben, Sanja; Brooks, Erin; Nair, Ajith P.; Heck, Kent A.; Rali, Aniket S.; Simpson, Leo; Saririan, Mehrdad; Hobohm, Dan; Stump, W. Tom; Fitzpatrick, James A.; Xie, Xuping; Shi, Pei-Yong; Hinson, J. Travis; Gi, Weng-Tein; Schmidt, Constanze; Leuschner, Florian; Lin, Chieh-Yu; Diamond, Michael S.; Greenberg, Michael J.; Lavine, Kory J. title: SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.04.364315 sha: doc_id: 270550 cord_uid: if748w2n file: cache/cord-270698-9w3ap3gz.json key: cord-270698-9w3ap3gz authors: Guo, Hua; Hu, Bing-Jie; Yang, Xing-Lou; Zeng, Lei-Ping; Li, Bei; Ouyang, Song-Ying; Shi, Zheng-Li title: Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes date: 2020-05-13 journal: bioRxiv DOI: 10.1101/2020.05.13.093658 sha: doc_id: 270698 cord_uid: 9w3ap3gz file: cache/cord-267831-uu883ofc.json key: cord-267831-uu883ofc authors: Kang, Yuan-Lin; Chou, Yi-Ying; Rothlauf, Paul W.; Liu, Zhuoming; Soh, Timothy K.; Cureton, David; Case, James Brett; Chen, Rita E.; Diamond, Michael S.; Whelan, Sean P. J.; Kirchhausen, Tom title: Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2 date: 2020-06-15 journal: bioRxiv DOI: 10.1101/2020.04.21.053058 sha: doc_id: 267831 cord_uid: uu883ofc file: cache/cord-271693-7tg21up3.json key: cord-271693-7tg21up3 authors: Zheng, Fan; Zhang, She; Churas, Christopher; Pratt, Dexter; Bahar, Ivet; Ideker, Trey title: Identifying persistent structures in multiscale ‘omics data date: 2020-10-03 journal: bioRxiv DOI: 10.1101/2020.06.16.151555 sha: doc_id: 271693 cord_uid: 7tg21up3 file: cache/cord-268034-7id7sfsu.json key: cord-268034-7id7sfsu authors: Auerswald, Heidi; Yann, Sokhoun; Dul, Sokha; In, Saraden; Dussart, Philippe; Martin, Nicholas J.; Karlsson, Erik A.; Garcia-Rivera, Jose A. title: Assessment of Inactivation Procedures for SARS-CoV-2 date: 2020-05-28 journal: bioRxiv DOI: 10.1101/2020.05.28.120444 sha: doc_id: 268034 cord_uid: 7id7sfsu file: cache/cord-271978-j5enftje.json key: cord-271978-j5enftje authors: Zoltán, Köntös title: In Vitro Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) date: 2020-11-10 journal: bioRxiv DOI: 10.1101/2020.11.07.370726 sha: doc_id: 271978 cord_uid: j5enftje file: cache/cord-270329-t60t639i.json key: cord-270329-t60t639i authors: Schloer, Sebastian; Brunotte, Linda; Mecate-Zambrano, Angeles; Zheng, Shuyu; Tang, Jing; Ludwig, Stephan; Rescher, Ursula title: Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro date: 2020-10-16 journal: bioRxiv DOI: 10.1101/2020.10.16.342410 sha: doc_id: 270329 cord_uid: t60t639i file: cache/cord-270919-0hldozml.json key: cord-270919-0hldozml authors: Cortey, Martí; Li, Yanli; Díaz, Ivan; Clilverd, Hepzibar; Darwich, Laila; Mateu, Enric title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins date: 2020-05-17 journal: bioRxiv DOI: 10.1101/2020.05.16.099499 sha: doc_id: 270919 cord_uid: 0hldozml file: cache/cord-273416-332stbjl.json key: cord-273416-332stbjl authors: Liu, Tianyuan; Nogueira, Leandro Balzano; Lleo, Ana; Conesa, Ana title: Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease date: 2020-10-01 journal: bioRxiv DOI: 10.1101/2020.09.30.321059 sha: doc_id: 273416 cord_uid: 332stbjl file: cache/cord-261877-4y37676n.json key: cord-261877-4y37676n authors: Xu, Cong; Wang, Yanxing; Liu, Caixuan; Zhang, Chao; Han, Wenyu; Hong, Xiaoyu; Wang, Yifan; Hong, Qin; Wang, Shutian; Zhao, Qiaoyu; Wang, Yalei; Yang, Yong; Chen, Kaijian; Zheng, Wei; Kong, Liangliang; Wang, Fangfang; Zuo, Qinyu; Huang, Zhong; Cong, Yao title: Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.06.30.177097 sha: doc_id: 261877 cord_uid: 4y37676n file: cache/cord-271971-rstmd0va.json key: cord-271971-rstmd0va authors: Matsumura, Yasufumi; Shimizu, Tsunehiro; Noguchi, Taro; Nakano, Satoshi; Yamamoto, Masaki; Nagao, Miki title: Comparison of 12 molecular detection assays for SARS-CoV-2 date: 2020-06-25 journal: bioRxiv DOI: 10.1101/2020.06.24.170332 sha: doc_id: 271971 cord_uid: rstmd0va file: cache/cord-273882-tqdcb3oo.json key: cord-273882-tqdcb3oo authors: Pratibha,; Shaju, C.; Kamal, title: Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses date: 2020-08-21 journal: bioRxiv DOI: 10.1101/2020.08.21.261289 sha: doc_id: 273882 cord_uid: tqdcb3oo file: cache/cord-270257-5f95gve3.json key: cord-270257-5f95gve3 authors: Jeon, Sangeun; Ko, Meehyun; Lee, Jihye; Choi, Inhee; Byun, Soo Young; Park, Soonju; Shum, David; Kim, Seungtaek title: Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs date: 2020-03-28 journal: bioRxiv DOI: 10.1101/2020.03.20.999730 sha: doc_id: 270257 cord_uid: 5f95gve3 file: cache/cord-273645-czh3zfb3.json key: cord-273645-czh3zfb3 authors: Lu, Shuaiyao; Zhao, Yuan; Yu, Wenhai; Yang, Yun; Gao, Jiahong; Wang, Junbin; Kuang, Dexuan; Yang, Mengli; Yang, Jing; Ma, Chunxia; Xu, Jingwen; Qian, Xingli; Li, Haiyan; Zhao, Siwen; Li, Jingmei; Wang, Haixuan; Long, Haiting; Zhou, Jingxian; Luo, Fangyu; Ding, Kaiyun; Wu, Daoju; Zhang, Yong; Dong, Yinliang; Liu, Yuqin; Zheng, Yingqiu; Lin, Xiaochen; Jiao, Li; Zheng, Huanying; Dai, Qing; Sun, Qiangmin; Hu, Yunzhang; Ke, Changwen; Liu, Hongqi; Peng, Xiaozhong title: Comparison of SARS-CoV-2 infections among 3 species of non-human primates date: 2020-07-17 journal: bioRxiv DOI: 10.1101/2020.04.08.031807 sha: doc_id: 273645 cord_uid: czh3zfb3 file: cache/cord-273891-7w334xgt.json key: cord-273891-7w334xgt authors: Kirchdoerfer, Robert N.; Wang, Nianshuang; Pallesen, Jesper; Wrapp, Daniel; Turner, Hannah L.; Cottrell, Christopher A.; Corbett, Kizzmekia S.; Graham, Barney S.; McLellan, Jason S.; Ward, Andrew B. title: Receptor binding and proteolysis do not induce large conformational changes in the SARS-CoV spike date: 2018-03-31 journal: bioRxiv DOI: 10.1101/292672 sha: doc_id: 273891 cord_uid: 7w334xgt file: cache/cord-271970-i35pic5o.json key: cord-271970-i35pic5o authors: Boris, Bonaventure; Antoine, Rebendenne; de Gracia Francisco, Garcia; Marine, Tauziet; Joe, McKellar; Valadão Ana Luiza, Chaves; Valérie, Courgnaud; Eric, Bernard; Laurence, Briant; Nathalie, Gros; Wassila, Djilli; Mary, Arnaud-Arnould; Hugues, Parrinello; Stéphanie, Rialle; Olivier, Moncorgé; Caroline, Goujon title: A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date: 2020-10-28 journal: bioRxiv DOI: 10.1101/2020.10.28.359356 sha: doc_id: 271970 cord_uid: i35pic5o file: cache/cord-272513-umuiovrd.json key: cord-272513-umuiovrd authors: Bindayna, Khalid Mubarak; Crinion, Shane title: Variant analysis of SARS-CoV-2 genomes in the Middle East date: 2020-10-09 journal: bioRxiv DOI: 10.1101/2020.10.09.332692 sha: doc_id: 272513 cord_uid: umuiovrd file: cache/cord-275173-ely3aen3.json key: cord-275173-ely3aen3 authors: Pickering, Brad S.; Smith, Greg; Pinette, Mathieu M.; Embury-Hyatt, Carissa; Moffat, Estella; Marszal, Peter; Lewis, Charles E. title: Susceptibility of domestic swine to experimental infection with SARS-CoV-2 date: 2020-09-10 journal: bioRxiv DOI: 10.1101/2020.09.10.288548 sha: doc_id: 275173 cord_uid: ely3aen3 file: cache/cord-275252-4e3cn50u.json key: cord-275252-4e3cn50u authors: Rad SM, Ali Hosseini; McLellan, Alexander D. title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date: 2020-05-16 journal: bioRxiv DOI: 10.1101/2020.05.15.098947 sha: doc_id: 275252 cord_uid: 4e3cn50u file: cache/cord-275690-83nrzfon.json key: cord-275690-83nrzfon authors: Stanifer, Megan L.; Kee, Carmon; Cortese, Mirko; Triana, Sergio; Mukenhirn, Markus; Kraeusslich, Hans-Georg; Alexandrov, Theodore; Bartenschlager, Ralf; Boulant, Steeve title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 journal: bioRxiv DOI: 10.1101/2020.04.24.059667 sha: doc_id: 275690 cord_uid: 83nrzfon file: cache/cord-271849-wxmr8eki.json key: cord-271849-wxmr8eki authors: Meysman, Pieter; Postovskaya, Anna; De Neuter, Nicolas; Ogunjimi, Benson; Laukens, Kris title: Tracking SARS-CoV-2 T cells with epitope-T-cell receptor recognition models date: 2020-09-09 journal: bioRxiv DOI: 10.1101/2020.09.09.289355 sha: doc_id: 271849 cord_uid: wxmr8eki file: cache/cord-272869-381qupdn.json key: cord-272869-381qupdn authors: Mirvakili, Seyed M; Sim, Douglas; Langer, Robert title: Reverse Pneumatic Artificial Muscles for Application in Low-Cost Artificial Respirators date: 2020-05-21 journal: bioRxiv DOI: 10.1101/2020.05.20.107342 sha: doc_id: 272869 cord_uid: 381qupdn file: cache/cord-274528-mr81o9cu.json key: cord-274528-mr81o9cu authors: Li, Fei; Han, Ming; Dai, Pengfei; Xu, Wei; He, Juan; Tao, Xiaoting; Wu, Yang; Tong, Xinyuan; Xia, Xinyi; Guo, Wangxin; Zhou, Yunjiao; Li, Yunguang; Zhu, Yiqin; Zhang, Xiaoyu; Liu, Zhuang; Aji, Rebiguli; Cai, Xia; Li, Yutang; Qu, Di; Chen, Yu; Jiang, Shibo; Wang, Qiao; Ji, Hongbin; Xie, Youhua; Sun, Yihua; Lu, Lu; Gao, Dong title: Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide date: 2020-09-12 journal: bioRxiv DOI: 10.1101/2020.09.11.293035 sha: doc_id: 274528 cord_uid: mr81o9cu file: cache/cord-280392-ij5gtesw.json key: cord-280392-ij5gtesw authors: Gultom, Mitra; Licheri, Matthias; Laloli, Laura; Wider, Manon; Strässle, Marina; Steiner, Silvio; Kratzel, Annika; Thao, Tran Thi Nhu; Stalder, Hanspeter; Portmann, Jasmine; Holwerda, Melle; V’kovski, Philip; Ebert, Nadine; Stokar – Regenscheit, Nadine; Gurtner, Corinne; Zanolari, Patrik; Posthaus, Horst; Schuller, Simone; Vicente – Santos, Amanda; Moreira – Soto, Andres; Corrales – Aguilar, Eugenia; Ruggli, Nicolas; Tekes, Gergely; von Messling, Veronika; Sawatsky, Bevan; Thiel, Volker; Dijkman, Ronald title: Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2 date: 2020-11-10 journal: bioRxiv DOI: 10.1101/2020.11.10.374587 sha: doc_id: 280392 cord_uid: ij5gtesw file: cache/cord-272986-ebgusf3o.json key: cord-272986-ebgusf3o authors: Cao, Yipeng; Yang, Rui; Wang, Wei; Lee, Imshik; Zhang, Ruiping; Zhang, Wenwen; Sun, Jiana; Xu, Bo; Meng, Xiangfei title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel date: 2020-05-17 journal: bioRxiv DOI: 10.1101/2020.05.17.099143 sha: doc_id: 272986 cord_uid: ebgusf3o file: cache/cord-274409-4ugdxbmy.json key: cord-274409-4ugdxbmy authors: Laskar, Rezwanuzzaman; Ali, Safdar title: Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2020.10.19.345066 sha: doc_id: 274409 cord_uid: 4ugdxbmy file: cache/cord-272626-bw9lbzvt.json key: cord-272626-bw9lbzvt authors: Pizzorno, Andrés; Padey, Blandine; Julien, Thomas; Trouillet-Assant, Sophie; Traversier, Aurélien; Errazuriz-Cerda, Elisabeth; Fouret, Julien; Dubois, Julia; Gaymard, Alexandre; Lescure, François-Xavier; Dulière, Victoria; Brun, Pauline; Constant, Samuel; Poissy, Julien; Lina, Bruno; Yazdanpanah, Yazdan; Terrier, Olivier; Rosa-Calatrava, Manuel title: Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia date: 2020-04-02 journal: bioRxiv DOI: 10.1101/2020.03.31.017889 sha: doc_id: 272626 cord_uid: bw9lbzvt file: cache/cord-274114-fglyfz8p.json key: cord-274114-fglyfz8p authors: Minervina, Anastasia A.; Komech, Ekaterina A.; Titov, Aleksei; Koraichi, Meriem Bensouda; Rosati, Elisa; Mamedov, Ilgar Z.; Franke, Andre; Efimov, Grigory A.; Chudakov, Dmitriy M.; Mora, Thierry; Walczak, Aleksandra M.; Lebedev, Yuri B.; Pogorelyy, Mikhail V. title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection date: 2020-10-01 journal: bioRxiv DOI: 10.1101/2020.05.18.100545 sha: doc_id: 274114 cord_uid: fglyfz8p file: cache/cord-279474-c5y2lygj.json key: cord-279474-c5y2lygj authors: Bozzo, Caterina Prelli; Nchioua, Rayhane; Volcic, Meta; Wettstein, Lukas; Weil, Tatjana; Krüger, Jana; Heller, Sandra; Conzelmann, Carina; Müller, Janis; Gross, Rüdiger; Zech, Fabian; Schütz, Desiree; Koepke, Lennart; Stuerzel, Christina M; Schüler, Christiane; Stenzel, Saskia; Braun, Elisabeth; Weiß, Johanna; Sauter, Daniel; Münch, Jan; Stenger, Steffen; Sato, Kei; Kleger, Alexander; Goffinet, Christine; Sparrer, Konstantin M.J.; Kirchhoff, Frank title: IFITM proteins promote SARS-CoV-2 infection of human lung cells date: 2020-08-18 journal: bioRxiv DOI: 10.1101/2020.08.18.255935 sha: doc_id: 279474 cord_uid: c5y2lygj file: cache/cord-279629-t1xjy12y.json key: cord-279629-t1xjy12y authors: Nazneen Akhand, Mst Rubaiat; Azim, Kazi Faizul; Hoque, Syeda Farjana; Moli, Mahmuda Akther; Joy, Bijit Das; Akter, Hafsa; Afif, Ibrahim Khalil; Ahmed, Nadim; Hasan, Mahmudul title: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date: 2020-04-15 journal: bioRxiv DOI: 10.1101/2020.04.15.036285 sha: doc_id: 279629 cord_uid: t1xjy12y file: cache/cord-278869-7zr1118b.json key: cord-278869-7zr1118b authors: Ravichandran, Supriya; Coyle, Elizabeth M.; Klenow, Laura; Tang, Juanjie; Grubbs, Gabrielle; Liu, Shufeng; Wang, Tony; Golding, Hana; Khurana, Surender title: Antibody repertoire induced by SARS-CoV-2 spike protein immunogens date: 2020-05-13 journal: bioRxiv DOI: 10.1101/2020.05.12.091918 sha: doc_id: 278869 cord_uid: 7zr1118b file: cache/cord-280454-etf32afd.json key: cord-280454-etf32afd authors: Moustaqil, Mehdi; Ollivier, Emma; Chiu, Hsin-Ping; Van Tol, Sarah; Rudolffi-Soto, Paulina; Stevens, Christian; Bhumkar, Akshay; Hunter, Dominic J.B.; Freiberg, Alex; Jacques, David; Lee, Benhur; Sierecki, Emma; Gambin, Yann title: SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts date: 2020-06-05 journal: bioRxiv DOI: 10.1101/2020.06.05.135699 sha: doc_id: 280454 cord_uid: etf32afd file: cache/cord-273613-cpiveo7j.json key: cord-273613-cpiveo7j authors: Cao, Xia; Maruyama, Junki; Zhou, Heyue; Kerwin, Lisa; Sattler, Rachel; Manning, John T.; Johnson, Sachi; Richards, Susan; Li, Yan; Shen, Weiqun; Blair, Benjamin; Du, Na; Morais, Kyndal; Lawrence, Kate; Lu, Lucy; Pai, Chin-I; Li, Donghui; Brunswick, Mark; Zhang, Yanliang; Ji, Henry; Paessler, Slobodan; Allen, Robert D. title: Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach date: 2020-09-29 journal: bioRxiv DOI: 10.1101/2020.09.27.316174 sha: doc_id: 273613 cord_uid: cpiveo7j file: cache/cord-276017-2375ipkk.json key: cord-276017-2375ipkk authors: Chen, Dongsheng; Sun, Jian; Zhu, Jiacheng; Ding, Xiangning; Lan, Tianming; Zhu, Linnan; Xiang, Rong; Ding, Peiwen; Wang, Haoyu; Wang, Xiaoling; Wu, Weiying; Qiu, Jiaying; Wang, Shiyou; Li, Haimeng; An, Fuyu; Bao, Heng; Zhang, Le; Han, Lei; Zhu, Yixin; Wang, Xiran; Wang, Feiyue; Yuan, Yuting; Wu, Wendi; Sun, Chengcheng; Lu, Haorong; Wu, Jihong; Sun, Xinghuai; Zhang, Shenghai; Sahu, Sunil Kumar; Chen, Haixia; Fang, Dongming; Luo, Lihua; Zeng, Yuying; Wu, Yiquan; Cui, ZeHua; He, Qian; Jiang, Sanjie; Ma, Xiaoyan; Feng, Weimin; Xu, Yan; Li, Fang; Liu, Zhongmin; Chen, Lei; Chen, Fang; Jin, Xin; Qiu, Wei; Yang, Huanming; Wang, Jian; Hua, Yan; Liu, Yahong; Liu, Huan; Xu, Xun title: Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife date: 2020-06-14 journal: bioRxiv DOI: 10.1101/2020.06.13.149690 sha: doc_id: 276017 cord_uid: 2375ipkk file: cache/cord-280994-w8dtfjel.json key: cord-280994-w8dtfjel authors: Peng, Qi; Peng, Ruchao; Yuan, Bin; Zhao, Jingru; Wang, Min; Wang, Xixi; Wang, Qian; Sun, Yan; Fan, Zheng; Qi, Jianxun; Gao, George F.; Shi, Yi title: Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from COVID-19 virus date: 2020-04-23 journal: bioRxiv DOI: 10.1101/2020.04.23.057265 sha: doc_id: 280994 cord_uid: w8dtfjel file: cache/cord-273083-xrydkiu4.json key: cord-273083-xrydkiu4 authors: Pahmeier, Felix; Neufeldt, Christoper J; Cerikan, Berati; Prasad, Vibhu; Pape, Costantin; Laketa, Vibor; Ruggieri, Alessia; Bartenschlager, Ralf; Cortese, Mirko title: A versatile reporter system to monitor virus infected cells and its application to dengue virus and SARS-CoV-2 date: 2020-09-01 journal: bioRxiv DOI: 10.1101/2020.08.31.276683 sha: doc_id: 273083 cord_uid: xrydkiu4 file: cache/cord-277253-vy0mvzeb.json key: cord-277253-vy0mvzeb authors: Liu, Hongbo; Ye, Fei; Sun, Qi; Liang, Hao; Li, Chunmei; Lu, Roujian; Huang, Baoying; Tan, Wenjie; Lai, Luhua title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.10.035824 sha: doc_id: 277253 cord_uid: vy0mvzeb file: cache/cord-277487-jgbjxgh1.json key: cord-277487-jgbjxgh1 authors: Graham, Simon P.; McLean, Rebecca K.; Spencer, Alexandra J.; Belij-Rammerstorfer, Sandra; Wright, Daniel; Ulaszewska, Marta; Edwards, Jane C.; Hayes, Jack W. P.; Martini, Veronica; Thakur, Nazia; Conceicao, Carina; Dietrich, Isabelle; Shelton, Holly; Waters, Ryan; Ludi, Anna; Wilsden, Ginette; Browning, Clare; Bialy, Dagmara; Bhat, Sushant; Stevenson-Leggett, Phoebe; Hollinghurst, Philippa; Gilbride, Ciaran; Pulido, David; Moffat, Katy; Sharpe, Hannah; Allen, Elizabeth; Mioulet, Valerie; Chiu, Chris; Newman, Joseph; Asfor, Amin S.; Burman, Alison; Crossley, Sylvia; Huo, Jiandong; Owens, Raymond J.; Carroll, Miles; Hammond, John A.; Tchilian, Elma; Bailey, Dalan; Charleston, Bryan; Gilbert, Sarah C.; Tuthill, Tobias J.; Lambe, Teresa title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 journal: bioRxiv DOI: 10.1101/2020.06.20.159715 sha: doc_id: 277487 cord_uid: jgbjxgh1 file: cache/cord-281684-m3m4mhye.json key: cord-281684-m3m4mhye authors: Fagre, Anna C.; Manhard, John; Adams, Rachel; Eckley, Miles; Zhan, Shijun; Lewis, Juliette; Rocha, Savannah M.; Woods, Catherine; Kuo, Karina; Liao, Wuxiang; Li, Lin; Corper, Adam; Challa, Dilip; Mount, Emily; Tumanut, Christine; Tjalkens, Ronald B.; Aboelleil, Tawfik; Fan, Xiaomin; Schountz, Tony title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date: 2020-09-28 journal: bioRxiv DOI: 10.1101/2020.09.25.313601 sha: doc_id: 281684 cord_uid: m3m4mhye file: cache/cord-281699-pxof67pl.json key: cord-281699-pxof67pl authors: Eskier, Doğa; Suner, Aslı; Oktay, Yavuz; Karakülah, Gökhan title: Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load date: 2020-08-13 journal: bioRxiv DOI: 10.1101/2020.08.12.248732 sha: doc_id: 281699 cord_uid: pxof67pl file: cache/cord-277648-9kxwkcbl.json key: cord-277648-9kxwkcbl authors: Overholt, Kalon J.; Krog, Jonathan R.; Bryson, Bryan D. title: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.15.147470 sha: doc_id: 277648 cord_uid: 9kxwkcbl file: cache/cord-282372-nmii30mc.json key: cord-282372-nmii30mc authors: Youk, Jeonghwan; Kim, Taewoo; Evans, Kelly V.; Jeong, Young-Il; Hur, Yongsuk; Hong, Seon Pyo; Kim, Je Hyoung; Yi, Kijong; Kim, Su Yeon; Na, Kwon Joong; Bleazard, Thomas; Kim, Ho Min; Ivory, Natasha; Mahbubani, Krishnaa T.; Saeb-Parsy, Kourosh; Kim, Young Tae; Koh, Gou Young; Choi, Byeong-Sun; Ju, Young Seok; Lee, Joo-Hyeon title: Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection date: 2020-07-10 journal: bioRxiv DOI: 10.1101/2020.07.10.194498 sha: doc_id: 282372 cord_uid: nmii30mc file: cache/cord-279576-wt4crton.json key: cord-279576-wt4crton authors: Fajardo, Álvaro; Pereira-Gómez, Marianoel; Echeverría, Natalia; López-Tort, Fernando; Perbolianachis, Paula; Aldunate, Fabián; Moreno, Pilar; Moratorio, Gonzalo title: Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples date: 2020-05-13 journal: bioRxiv DOI: 10.1101/2020.05.13.093609 sha: doc_id: 279576 cord_uid: wt4crton file: cache/cord-284102-rovyvv45.json key: cord-284102-rovyvv45 authors: Wagner, Teresa R.; Kaiser, Philipp D.; Gramlich, Marius; Becker, Matthias; Traenkle, Bjoern; Junker, Daniel; Haering, Julia; Dulovic, Alex; Schweizer, Helen; Nueske, Stefan; Scholz, Armin; Zeck, Anne; Schenke-Layland, Katja; Nelde, Annika; Strengert, Monika; Walz, Juliane S.; Ruetalo, Natalia; Schindler, Michael; Schneiderhan-Marra, Nicole; Rothbauer, Ulrich title: NeutrobodyPlex - Nanobodies to monitor a SARS-CoV-2 neutralizing immune response date: 2020-09-28 journal: bioRxiv DOI: 10.1101/2020.09.22.308338 sha: doc_id: 284102 cord_uid: rovyvv45 file: cache/cord-280198-bhjw6xc5.json key: cord-280198-bhjw6xc5 authors: Olaleye, Omonike A.; Kaur, Manvir; Onyenaka, Collins; Adebusuyi, Tolu title: Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.08.14.250480 sha: doc_id: 280198 cord_uid: bhjw6xc5 file: cache/cord-280979-0vaarrji.json key: cord-280979-0vaarrji authors: Gauttier, V.; Morello, A.; Girault, I.; Mary, C.; Belarif, L.; Desselle, A.; Wilhelm, E.; Bourquard, T.; Pengam, S.; Teppaz, G.; Thepenier, V.; Biteau, K.; De Barbeyrac, E.; Kiepferlé, D.; Vasseur, B.; Le Flem, FX.; Debieuvre, D.; Costantini, D.; Poirier, N. title: Tissue-resident memory CD8 T-cell responses elicited by a single injection of a multi-target COVID-19 vaccine date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.08.14.240093 sha: doc_id: 280979 cord_uid: 0vaarrji file: cache/cord-284354-aoti88v7.json key: cord-284354-aoti88v7 authors: Lupala, Cecylia S.; Kumar, Vikash; Li, Xuanxuan; Su, Xiao-dong; Liu, Haiguang title: Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 date: 2020-05-04 journal: bioRxiv DOI: 10.1101/2020.05.03.075473 sha: doc_id: 284354 cord_uid: aoti88v7 file: cache/cord-280922-w6a5ec06.json key: cord-280922-w6a5ec06 authors: Sen, Sanjana; Sanders, Emily C.; Gabriel, Kristin N.; Miller, Brian M.; Isoda, Hariny M.; Salcedo, Gabriela S.; Garrido, Jason E.; Dyer, Rebekah P.; Nakajima, Rie; Jain, Aarti; Santos, Alicia M.; Bhuvan, Keertna; Tifrea, Delia F.; Ricks-Oddie, Joni L.; Felgner, Philip L.; Edwards, Robert A.; Majumdar, Sudipta; Weiss, Gregory A. title: Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score date: 2020-10-29 journal: bioRxiv DOI: 10.1101/2020.10.15.341743 sha: doc_id: 280922 cord_uid: w6a5ec06 file: cache/cord-282795-kje7rn57.json key: cord-282795-kje7rn57 authors: Zheng, Yue; Larragoite, Erin T.; Lama, Juan; Cisneros, Isabel; Delgado, Julio C.; Slev, Patricia; Rychert, Jenna; Innis, Emily A.; Williams, Elizabeth S.C.P.; Coiras, Mayte; Rondina, Matthew T.; Spivak, Adam M.; Planelles, Vicente title: Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions date: 2020-09-21 journal: bioRxiv DOI: 10.1101/2020.07.17.207563 sha: doc_id: 282795 cord_uid: kje7rn57 file: cache/cord-280025-4hmecfi0.json key: cord-280025-4hmecfi0 authors: Korber, B; Fischer, WM; Gnanakaran, S; Yoon, H; Theiler, J; Abfalterer, W; Foley, B; Giorgi, EE; Bhattacharya, T; Parker, MD; Partridge, DG; Evans, CM; Freeman, TM; de Silva, TI; LaBranche, CC; Montefiori, DC title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 date: 2020-05-05 journal: bioRxiv DOI: 10.1101/2020.04.29.069054 sha: doc_id: 280025 cord_uid: 4hmecfi0 file: cache/cord-281717-kzd9vvci.json key: cord-281717-kzd9vvci authors: Digard, Paul; Lee, Hui Min; Sharp, Colin; Grey, Finn; Gaunt, Eleanor title: Intra-genome variability in the dinucleotide composition of SARS-CoV-2 date: 2020-05-08 journal: bioRxiv DOI: 10.1101/2020.05.08.083816 sha: doc_id: 281717 cord_uid: kzd9vvci file: cache/cord-282604-xp71rkxc.json key: cord-282604-xp71rkxc authors: Nikolaev, EN; Indeykina, MI; Brzhozovskiy, AG; Bugrova, AE; Kononikhin, AS; Starodubtseva, NL; Petrotchenko, EV; Kovalev, G; Borchers, CH; Sukhikh, GT title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date: 2020-05-25 journal: bioRxiv DOI: 10.1101/2020.05.24.113043 sha: doc_id: 282604 cord_uid: xp71rkxc file: cache/cord-282878-8qgsq2km.json key: cord-282878-8qgsq2km authors: Fignani, Daniela; Licata, Giada; Brusco, Noemi; Nigi, Laura; Grieco, Giuseppina E.; Marselli, Lorella; Overbergh, Lut; Gysemans, Conny; Colli, Maikel L.; Marchetti, Piero; Mathieu, Chantal; Eizirik, Decio L.; Sebastiani, Guido; Dotta, Francesco title: SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature date: 2020-10-23 journal: bioRxiv DOI: 10.1101/2020.07.23.208041 sha: doc_id: 282878 cord_uid: 8qgsq2km file: cache/cord-284045-scd3f8vk.json key: cord-284045-scd3f8vk authors: Pape, Constantin; Remme, Roman; Wolny, Adrian; Olberg, Sylvia; Wolf, Steffen; Cerrone, Lorenzo; Cortese, Mirko; Klaus, Severina; Lucic, Bojana; Ullrich, Stephanie; Anders-Össwein, Maria; Wolf, Stefanie; Cerikan, Berati; Neufeldt, Christopher J.; Ganter, Markus; Schnitzler, Paul; Merle, Uta; Lusic, Marina; Boulant, Steeve; Stanifer, Megan; Bartenschlager, Ralf; Hamprecht, Fred A.; Kreshuk, Anna; Tischer, Christian; Kräusslich, Hans-Georg; Müller, Barbara; Laketa, Vibor title: Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.06.15.152587 sha: doc_id: 284045 cord_uid: scd3f8vk file: cache/cord-281141-ouno4jpl.json key: cord-281141-ouno4jpl authors: Mahajan, Swapnil; Kode, Vasumathi; Bhojak, Keshav; Magdalene, Coral M.; Lee, Kayla; Manoharan, Malini; Ramesh, Athulya; Sudheendra, HV; Srivastava, Ankita; Sathian, Rekha; Khan, Tahira; Kumar, Prasanna; Chakraborty, Papia; Chaudhuri, Amitabha title: Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.03.367375 sha: doc_id: 281141 cord_uid: ouno4jpl file: cache/cord-283109-ka3n9pft.json key: cord-283109-ka3n9pft authors: Arumugam, Arunkumar; Wong, Season title: The Potential Use of Unprocessed Sample for RT-qPCR Detection of COVID-19 without an RNA Extraction Step date: 2020-04-08 journal: bioRxiv DOI: 10.1101/2020.04.06.028811 sha: doc_id: 283109 cord_uid: ka3n9pft file: cache/cord-285159-gytebbua.json key: cord-285159-gytebbua authors: Eydoux, Cecilia; Fattorini, Veronique; Shannon, Ashleigh; Le, Thi-Tuyet-Nhung; Didier, Bruno; Canard, Bruno; Guillemot, Jean-Claude title: A Fluorescence-based High Throughput-Screening assay for the SARS-CoV RNA synthesis complex date: 2020-07-07 journal: bioRxiv DOI: 10.1101/2020.07.07.192005 sha: doc_id: 285159 cord_uid: gytebbua file: cache/cord-284068-sbon3aes.json key: cord-284068-sbon3aes authors: Mok, Chee Keng; Ng, Yan Ling; Ahidjo, Bintou Ahmadou; Hua Lee, Regina Ching; Choy Loe, Marcus Wing; Liu, Jing; Tan, Kai Sen; Kaur, Parveen; Chng, Wee Joo; Wong, John Eu-Li; Wang, De Yun; Hao, Erwei; Hou, Xiaotao; Tan, Yong Wah; Mak, Tze Minn; Lin, Cui; Lin, Raymond; Tambyah, Paul; Deng, JiaGang; Hann Chu, Justin Jang title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date: 2020-06-22 journal: bioRxiv DOI: 10.1101/2020.06.21.162396 sha: doc_id: 284068 cord_uid: sbon3aes file: cache/cord-284627-qvz63m93.json key: cord-284627-qvz63m93 authors: Banerjee, Shuvam; Dhar, Shrinjana; Bhattacharjee, Sandip; Bhattacharjee, Pritha title: Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence date: 2020-04-09 journal: bioRxiv DOI: 10.1101/2020.04.06.027854 sha: doc_id: 284627 cord_uid: qvz63m93 file: cache/cord-286001-pu1fetq7.json key: cord-286001-pu1fetq7 authors: Zang, Ruochen; Castro, Maria F.G.; McCune, Broc T.; Zeng, Qiru; Rothlauf, Paul W.; Sonnek, Naomi M.; Liu, Zhuoming; Brulois, Kevin F.; Wang, Xin; Greenberg, Harry B.; Diamond, Michael S.; Ciorba, Matthew A.; Whelan, Sean P.J.; Ding, Siyuan title: TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes date: 2020-04-23 journal: bioRxiv DOI: 10.1101/2020.04.21.054015 sha: doc_id: 286001 cord_uid: pu1fetq7 file: cache/cord-284191-05djnz4p.json key: cord-284191-05djnz4p authors: Bert, Nina Le; Tan, Anthony T; Kunasegaran, Kamini; Tham, Christine Y L; Hafezi, Morteza; Chia, Adeline; Chng, Melissa; Lin, Meiyin; Tan, Nicole; Linster, Martin; Chia, Wan Ni; Chen, Mark I-Cheng; Wang, Lin-Fa; Ooi, Eng Eong; Kalimuddin, Shirin; Tambyah, Paul Anantharajal; Low, Jenny Guek-Hong; Tan, Yee-Joo; Bertoletti, Antonio title: Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals date: 2020-05-27 journal: bioRxiv DOI: 10.1101/2020.05.26.115832 sha: doc_id: 284191 cord_uid: 05djnz4p file: cache/cord-286810-kq2gu5cc.json key: cord-286810-kq2gu5cc authors: Klein, Joshua A.; Zaia, Joseph title: Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft date: 2020-05-31 journal: bioRxiv DOI: 10.1101/2020.05.31.125302 sha: doc_id: 286810 cord_uid: kq2gu5cc file: cache/cord-286466-scokdxp2.json key: cord-286466-scokdxp2 authors: Tani, Hideki; Tan, Long; Kimura, Miyuki; Yoshida, Yoshihiro; Yamada, Hiroshi; Fukushi, Shuetsu; Saijo, Masayuki; Kawasuji, Hitoshi; Ueno, Akitoshi; Miyajima, Yuki; Fukui, Yasutaka; Sakamaki, Ippei; Yamamoto, Yoshihiro; Morinaga, Yoshitomo title: Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein date: 2020-08-23 journal: bioRxiv DOI: 10.1101/2020.08.21.262295 sha: doc_id: 286466 cord_uid: scokdxp2 file: cache/cord-285592-0in22wzv.json key: cord-285592-0in22wzv authors: Lemoine, Frédéric; Blassel, Luc; Voznica, Jakub; Gascuel, Olivier title: COVID-Align: Accurate online alignment of hCoV-19 genomes using a profile HMM date: 2020-05-25 journal: bioRxiv DOI: 10.1101/2020.05.25.114884 sha: doc_id: 285592 cord_uid: 0in22wzv file: cache/cord-287172-h8zoplkm.json key: cord-287172-h8zoplkm authors: Ghobrial, Moheb; Charish, Jason; Takada, Shigeki; Valiante, Taufik; Monnier, Philippe P.; Radovanovic, Ivan; Bader, Gary D.; Wälchli, Thomas title: The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors date: 2020-10-21 journal: bioRxiv DOI: 10.1101/2020.10.10.334664 sha: doc_id: 287172 cord_uid: h8zoplkm file: cache/cord-291012-y0ufzx93.json key: cord-291012-y0ufzx93 authors: Ye, Qing; Zhou, Jia; Yang, Guan; Li, Rui-Ting; He, Qi; Zhang, Yao; Wu, Shu-Jia; Chen, Qi; Shi, Jia-Hui; Zhang, Rong-Rong; Zhu, Hui-Min; Qiu, Hong-Ying; Zhang, Tao; Deng, Yong-Qiang; Li, Xiao-Feng; Xu, Ping; Yang, Xiao; Qin, Cheng-Feng title: SARS-CoV-2 infection causes transient olfactory dysfunction in mice date: 2020-11-10 journal: bioRxiv DOI: 10.1101/2020.11.10.376673 sha: doc_id: 291012 cord_uid: y0ufzx93 file: cache/cord-281565-v8s2ski3.json key: cord-281565-v8s2ski3 authors: Belmonte-Reche, Efres; Serrano-Chacón, Israel; Gonzalez, Carlos; Gallo, Juan; Bañobre-López, Manuel title: Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date: 2020-08-20 journal: bioRxiv DOI: 10.1101/2020.08.19.257493 sha: doc_id: 281565 cord_uid: v8s2ski3 file: cache/cord-285088-krim73zt.json key: cord-285088-krim73zt authors: Wang, Deguo title: One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay date: 2020-04-21 journal: bioRxiv DOI: 10.1101/2020.04.21.052530 sha: doc_id: 285088 cord_uid: krim73zt file: cache/cord-281679-xmbnpawj.json key: cord-281679-xmbnpawj authors: Meekins, David A.; Morozov, Igor; Trujillo, Jessie D.; Gaudreault, Natasha N.; Bold, Dashzeveg; Artiaga, Bianca L.; Indran, Sabarish V.; Kwon, Taeyong; Balaraman, Velmurugan; Madden, Daniel W.; Feldmann, Heinz; Henningson, Jamie; Ma, Wenjun; Balasuriya, Udeni B. R.; Richt, Juergen A. title: Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.08.15.252395 sha: doc_id: 281679 cord_uid: xmbnpawj file: cache/cord-287658-c2lljdi7.json key: cord-287658-c2lljdi7 authors: Lopez-Rincon, Alejandro; Tonda, Alberto; Mendoza-Maldonado, Lucero; Mulders, Daphne G.J.C.; Molenkamp, Richard; Perez-Romero, Carmina A.; Claassen, Eric; Garssen, Johan; Kraneveld, Aletta D. title: Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date: 2020-09-10 journal: bioRxiv DOI: 10.1101/2020.03.13.990242 sha: doc_id: 287658 cord_uid: c2lljdi7 file: cache/cord-291710-ixun0c8g.json key: cord-291710-ixun0c8g authors: Su, Haixia; Yao, Sheng; Zhao, Wenfeng; Li, Minjun; Liu, Jia; Shang, WeiJuan; Xie, Hang; Ke, Changqiang; Gao, Meina; Yu, Kunqian; Liu, Hong; Shen, Jingshan; Tang, Wei; Zhang, Leike; Zuo, Jianping; Jiang, Hualiang; Bai, Fang; Wu, Yan; Ye, Yang; Xu, Yechun title: Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.13.038687 sha: doc_id: 291710 cord_uid: ixun0c8g file: cache/cord-290445-vb53bih9.json key: cord-290445-vb53bih9 authors: Ahmed, Shiek SSJ; Paramasivam, Prabu; Raj, Kamal; Kumar, Vishal; murugesan, Ram; Ramakrishnan, title: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date: 2020-04-23 journal: bioRxiv DOI: 10.1101/2020.04.20.050138 sha: doc_id: 290445 cord_uid: vb53bih9 file: cache/cord-291420-40xsypzt.json key: cord-291420-40xsypzt authors: Nelson-Sathi, Shijulal; Umasankar, PK; Sreekumar, E; Radhakrishnan Nair, R; Joseph, Iype; Nori, Sai Ravi Chandra; Philip, Jamiema Sara; Prasad, Roshny; Navyasree, KV; Ramesh, Shikha; Pillai, Heera; Ghosh, Sanu; Santosh Kumar, TR; Radhakrishna Pillai, M. title: Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction date: 2020-10-01 journal: bioRxiv DOI: 10.1101/2020.05.02.071811 sha: doc_id: 291420 cord_uid: 40xsypzt file: cache/cord-288705-f3zqhpx1.json key: cord-288705-f3zqhpx1 authors: Slaine, Patrick; Kleer, Mariel; Duguay, Brett; Pringle, Eric S.; Kadijk, Eileigh; Ying, Shan; Balgi, Aruna D.; Roberge, Michel; McCormick, Craig; Khaperskyy, Denys A. title: Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model date: 2020-10-01 journal: bioRxiv DOI: 10.1101/2020.09.30.319863 sha: doc_id: 288705 cord_uid: f3zqhpx1 file: cache/cord-290694-jmav8xi4.json key: cord-290694-jmav8xi4 authors: Bridgland, Victoria M. E.; Moeck, Ella K.; Green, Deanne M.; Swain, Taylor L.; Nayda, Diane; Matson, Lucy A.; Hutchison, Nadine P.; Takarangi, Melanie K.T. title: Why the COVID-19 pandemic is a traumatic stressor date: 2020-09-22 journal: bioRxiv DOI: 10.1101/2020.09.22.307637 sha: doc_id: 290694 cord_uid: jmav8xi4 file: cache/cord-291677-zcbyhsf1.json key: cord-291677-zcbyhsf1 authors: Wilamowski, M.; Sherrell, D.A.; Minasov, G.; Kim, Y.; Shuvalova, L.; Lavens, A.; Chard, R.; Maltseva, N.; Jedrzejczak, R.; Rosas-Lemus, M.; Saint, N.; Foster, I.T.; Michalska, K.; Satchell, K.J.F.; Joachimiak, A title: Methylation of RNA Cap in SARS-CoV-2 captured by serial crystallography date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.08.14.251421 sha: doc_id: 291677 cord_uid: zcbyhsf1 file: cache/cord-287205-k64svq6n.json key: cord-287205-k64svq6n authors: Pollet, Jeroen; Chen, Wen-Hsiang; Versteeg, Leroy; Keegan, Brian; Zhan, Bin; Wei, Junfei; Liu, Zhuyun; Lee, Jungsoon; Kundu, Rahki; Adhikari, Rakesh; Poveda, Cristina; Mondragon, Maria-Jose Villar; de Araujo Leao, Ana Carolina; Rivera, Joanne Altieri; Gillespie, Portia M.; Strych, Ulrich; Hotez, Peter J.; Bottazzi, Maria Elena title: SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.04.367359 sha: doc_id: 287205 cord_uid: k64svq6n file: cache/cord-291590-24psoaer.json key: cord-291590-24psoaer authors: Ogando, Natacha S.; Zevenhoven-Dobbe, Jessika C.; Posthuma, Clara C.; Snijder, Eric J. title: The enzymatic activity of the nsp14 exoribonuclease is critical for replication of Middle East respiratory syndrome-coronavirus date: 2020-06-20 journal: bioRxiv DOI: 10.1101/2020.06.19.162529 sha: doc_id: 291590 cord_uid: 24psoaer file: cache/cord-293640-pgrrurrc.json key: cord-293640-pgrrurrc authors: Tripathi, Satyendra C; Deshmukh, Vishwajit; Creighton, Chad J.; Patil, Ashlesh title: Renal carcinoma is associated with increased risk of coronavirus infections date: 2020-07-06 journal: bioRxiv DOI: 10.1101/2020.07.02.184663 sha: doc_id: 293640 cord_uid: pgrrurrc file: cache/cord-289367-zna8qkkv.json key: cord-289367-zna8qkkv authors: Wirden, Marc; Feghoul, Linda; Bertine, Mélanie; Nere, Marie-Laure; Le Hingrat, Quentin; Abdi, Basma; Boutolleau, David; Ferre, Valentine Marie; Jary, Aude; Delaugerre, Constance; Marcelin, Anne-Genevieve; Descamps, Diane; Legoff, Jérôme; Visseaux, Benoit; Chaix, Marie-Laure title: Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2 date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.06.29.179184 sha: doc_id: 289367 cord_uid: zna8qkkv file: cache/cord-290290-wyx9ib7s.json key: cord-290290-wyx9ib7s authors: Sinegubova, Maria V.; Orlova, Nadezhda A.; Kovnir, Sergey V.; Dayanova, Lutsia K.; Vorobiev, Ivan I title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.04.368092 sha: doc_id: 290290 cord_uid: wyx9ib7s file: cache/cord-291523-4dtk1kyh.json key: cord-291523-4dtk1kyh authors: Nguyen, Thanh Thi; Abdelrazek, Mohamed; Nguyen, Dung Tien; Aryal, Sunil; Nguyen, Duc Thanh; Khatami, Amin title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.05.12.091397 sha: doc_id: 291523 cord_uid: 4dtk1kyh file: cache/cord-293274-ysr1l557.json key: cord-293274-ysr1l557 authors: Perisé-Barrios, Ana Judith; Tomeo-Martín, Beatriz Davinia; Gómez-Ochoa, Pablo; Delgado-Bonet, Pablo; Plaza, Pedro; Palau-Concejo, Paula; González, Jorge; Ortiz-Diez, Gustavo; Meléndez-Lazo, Antonio; Gentil, Michaela; García-Castro, Javier; Barbero-Fernández, Alicia title: Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date: 2020-09-22 journal: bioRxiv DOI: 10.1101/2020.09.22.308023 sha: doc_id: 293274 cord_uid: ysr1l557 file: cache/cord-287372-ya5uvoki.json key: cord-287372-ya5uvoki authors: Böszörményi, Kinga P.; Stammes, Marieke A.; Fagrouch, Zahra C.; Kiemenyi-Kayere, Gwendoline; Niphuis, Henk; Mortier, Daniella; van Driel, Nikki; Nieuwenhuis, Ivonne; Zuiderwijk-Sick, Ella; Meijer, Lisette; Mooij, Petra; Remarque, Ed J.; Koopman, Gerrit; Hoste, Alexis C. R.; Sastre, Patricia; Haagmans, Bart L.; Bontrop, Ronald E.; Langermans, Jan A.M.; Bogers, Willy M.; Verschoor, Ernst J.; Verstrepen, Babs E. title: Comparison of SARS-CoV-2 infection in two non-human primate species: rhesus and cynomolgus macaques date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.05.369413 sha: doc_id: 287372 cord_uid: ya5uvoki file: cache/cord-291156-zxg3dsm3.json key: cord-291156-zxg3dsm3 authors: Bernasconi, Anna; Canakoglu, Arif; Pinoli, Pietro; Ceri, Stefano title: Empowering Virus Sequences Research through Conceptual Modeling date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.04.29.067637 sha: doc_id: 291156 cord_uid: zxg3dsm3 file: cache/cord-288644-ywaefpe8.json key: cord-288644-ywaefpe8 authors: Rodon, Jordi; Muñoz-Basagoiti, Jordana; Perez-Zsolt, Daniel; Noguera-Julian, Marc; Paredes, Roger; Mateu, Lourdes; Quiñones, Carles; Erkizia, Itziar; Blanco, Ignacio; Valencia, Alfonso; Guallar, Víctor; Carrillo, Jorge; Blanco, Julià; Segalés, Joaquim; Clotet, Bonaventura; Vergara-Alert, Júlia; Izquierdo-Useros, Nuria title: Pre-clinical search of SARS-CoV-2 inhibitors and their combinations in approved drugs to tackle COVID-19 pandemic date: 2020-10-20 journal: bioRxiv DOI: 10.1101/2020.04.23.055756 sha: doc_id: 288644 cord_uid: ywaefpe8 file: cache/cord-293428-8hj06hzt.json key: cord-293428-8hj06hzt authors: Yang, Jianling; Wu, Meng; Liu, Xu; Liu, Qi; Guo, Zhengyang; Yao, Xueting; Liu, Yang; Cui, Cheng; Li, Haiyan; Song, Chunli; Liu, Dongyang; Xue, Lixiang title: Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model date: 2020-04-24 journal: bioRxiv DOI: 10.1101/2020.04.22.056762 sha: doc_id: 293428 cord_uid: 8hj06hzt file: cache/cord-294120-8fxrqorg.json key: cord-294120-8fxrqorg authors: Guebre-Xabier, Mimi; Patel, Nita; Tian, Jing-Hui; Zhou, Bin; Maciejewski, Sonia; Lam, Kristal; Portnoff, Alyse D.; Massare, Michael J.; Frieman, Matthew B.; Piedra, Pedro A.; Ellingsworth, Larry; Glenn, Gregory; Smith, Gale title: NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge date: 2020-08-19 journal: bioRxiv DOI: 10.1101/2020.08.18.256578 sha: doc_id: 294120 cord_uid: 8fxrqorg file: cache/cord-295560-0rpguepv.json key: cord-295560-0rpguepv authors: Yan, Kexin; Rawle, Daniel J.; Le, Thuy T.T.; Suhrbier, Andreas title: Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.13.338541 sha: doc_id: 295560 cord_uid: 0rpguepv file: cache/cord-288824-sygnmiun.json key: cord-288824-sygnmiun authors: Lam, SD; Bordin, N; Waman, VP; Scholes, HM; Ashford, P; Sen, N; van Dorp, L; Rauer, C; Dawson, NL; Pang, CSM; Abbasian, M; Sillitoe, I; Edwards, SJL; Fraternali, F; Lees, JG; Santini, JM; Orengo, CA title: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals date: 2020-08-19 journal: bioRxiv DOI: 10.1101/2020.05.01.072371 sha: doc_id: 288824 cord_uid: sygnmiun file: cache/cord-295545-ruxz77i8.json key: cord-295545-ruxz77i8 authors: Hennighausen, Lothar; Lee, Hye Kyung title: Activation of the SARS-CoV-2 receptor Ace2 by cytokines through pan JAK-STAT enhancers date: 2020-05-11 journal: bioRxiv DOI: 10.1101/2020.05.11.089045 sha: doc_id: 295545 cord_uid: ruxz77i8 file: cache/cord-292862-ezrkg0dc.json key: cord-292862-ezrkg0dc authors: Myerson, Jacob W.; Patel, Priyal N.; Habibi, Nahal; Walsh, Landis R.; Lee, Yi-Wei; Luther, David C.; Ferguson, Laura T.; Zaleski, Michael H.; Zamora, Marco E.; Marcos-Contreras, Oscar A.; Glassman, Patrick M.; Johnston, Ian; Hood, Elizabeth D.; Shuvaeva, Tea; Gregory, Jason V.; Kiseleva, Raisa Y.; Nong, Jia; Rubey, Kathryn M.; Greineder, Colin F.; Mitragotri, Samir; Worthen, George S.; Rotello, Vincent M.; Lahann, Joerg; Muzykantov, Vladimir R.; Brenner, Jacob S. title: Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment date: 2020-04-18 journal: bioRxiv DOI: 10.1101/2020.04.15.037564 sha: doc_id: 292862 cord_uid: ezrkg0dc file: cache/cord-292985-w62xaa4f.json key: cord-292985-w62xaa4f authors: Römer, Rudolf A.; Römer, Navodya S.; Wallis, A. Katrine title: Flexibility and mobility of SARS-CoV-2-related protein structures date: 2020-07-12 journal: bioRxiv DOI: 10.1101/2020.07.12.199364 sha: doc_id: 292985 cord_uid: w62xaa4f file: cache/cord-292670-12prczym.json key: cord-292670-12prczym authors: Urra, José Miguel; Ferreras-Colino, Elisa; Contreras, Marinela; Cabrera, Carmen M.; Fernández de Mera, Isabel G.; Villar, Margarita; Cabezas-Cruz, Alejandro; Gortázar, Christian; de la Fuente, José title: The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms date: 2020-07-14 journal: bioRxiv DOI: 10.1101/2020.07.14.201954 sha: doc_id: 292670 cord_uid: 12prczym file: cache/cord-293826-2p7dqacd.json key: cord-293826-2p7dqacd authors: Lee, Cheryl Yi-Pin; Amrun, Siti Naqiah; Chee, Rhonda Sin-Ling; Goh, Yun Shan; Mak, Tze-Minn; Octavia, Sophie; Yeo, Nicholas Kim-Wah; Chang, Zi Wei; Tay, Matthew Zirui; Torres-Ruesta, Anthony; Carissimo, Guillaume; Poh, Chek Meng; Fong, Siew-Wai; Bei, Wang; Lee, Sandy; Young, Barnaby Edward; Tan, Seow-Yen; Leo, Yee-Sin; Lye, David C.; Lin, Raymond T. P.; Maurer-Stroh, Sebastien; Lee, Bernett; Cheng-I, Wang; Renia, Laurent; Ng, Lisa F.P. title: Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant date: 2020-10-09 journal: bioRxiv DOI: 10.1101/2020.10.08.332544 sha: doc_id: 293826 cord_uid: 2p7dqacd file: cache/cord-297021-fzfl08qa.json key: cord-297021-fzfl08qa authors: Manomaipiboon, Anan; Pupipatpab, Sujaree; Chomdee, Pongsathorn; Boonyapatkul, Pathiporn; Trakarnvanich, Thananda title: The new silicone N99 half-piece respirator, VJR-NMU N99: A novel and effective tool to prevent COVID-19 date: 2020-07-23 journal: bioRxiv DOI: 10.1101/2020.07.23.217372 sha: doc_id: 297021 cord_uid: fzfl08qa file: cache/cord-297754-d4xnj551.json key: cord-297754-d4xnj551 authors: Aktas, Emre title: Bioinformatic Analysis Reveals That Some Mutations May Affect On Both Spike Structure Damage and Ligand Binding Site date: 2020-09-03 journal: bioRxiv DOI: 10.1101/2020.08.10.244632 sha: doc_id: 297754 cord_uid: d4xnj551 file: cache/cord-296187-nnv2e7gr.json key: cord-296187-nnv2e7gr authors: Mulgaonkar, Nirmitee; Wang, Haoqi; Mallawarachchi, Samavath; Fernando, Sandun; Martina, Byron; Ruzek, Daniel title: Bcr-Abl tyrosine kinase inhibitor imatinib as a potential drug for COVID-19 date: 2020-08-18 journal: bioRxiv DOI: 10.1101/2020.06.18.158196 sha: doc_id: 296187 cord_uid: nnv2e7gr file: cache/cord-297775-ug4ovsws.json key: cord-297775-ug4ovsws authors: Hosie, Margaret J; Epifano, Ilaria; Herder, Vanessa; Orton, Richard J; Stevenson, Andrew; Johnson, Natasha; MacDonald, Emma; Dunbar, Dawn; McDonald, Michael; Howie, Fiona; Tennant, Bryn; Herrity, Darcy; Da Silva Filipe, Ana; Streicker, Daniel G; Willett, Brian J; Murcia, Pablo R; Jarrett, Ruth F; Robertson, David L; Weir, William title: Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK date: 2020-09-23 journal: bioRxiv DOI: 10.1101/2020.09.23.309948 sha: doc_id: 297775 cord_uid: ug4ovsws file: cache/cord-297787-t9neub6d.json key: cord-297787-t9neub6d authors: Fu, Ziyang; Huang, Bin; Tang, Jinle; Liu, Shuyan; Liu, Ming; Ye, Yuxin; Liu, Zhihong; Xiong, Yuxian; Cao, Dan; Li, Jihui; Niu, Xiaogang; Zhou, Huan; Zhao, Yong Juan; Zhang, Guoliang; Huang, Hao title: Structural basis for the inhibition of the papain-like protease of SARS-CoV-2 by small molecules date: 2020-07-18 journal: bioRxiv DOI: 10.1101/2020.07.17.208959 sha: doc_id: 297787 cord_uid: t9neub6d file: cache/cord-296997-ba7f2mf3.json key: cord-296997-ba7f2mf3 authors: Sikora, Mateusz; von Bülow, Sören; Blanc, Florian E. C.; Gecht, Michael; Covino, Roberto; Hummer, Gerhard title: Map of SARS-CoV-2 spike epitopes not shielded by glycans date: 2020-07-03 journal: bioRxiv DOI: 10.1101/2020.07.03.186825 sha: doc_id: 296997 cord_uid: ba7f2mf3 file: cache/cord-296657-mymndjvd.json key: cord-296657-mymndjvd authors: Higuchi, Yusuke; Suzuki, Tatsuya; Arimori, Takao; Ikemura, Nariko; Kirita, Yuhei; Ohgitani, Eriko; Mazda, Osam; Motooka, Daisuke; Nakamura, Shota; Matsuura, Yoshiharu; Matoba, Satoaki; Okamoto, Toru; Takagi, Junichi; Hoshino, Atsushi title: High affinity modified ACE2 receptors prevent SARS-CoV-2 infection date: 2020-09-16 journal: bioRxiv DOI: 10.1101/2020.09.16.299891 sha: doc_id: 296657 cord_uid: mymndjvd file: cache/cord-297684-9q3oopaz.json key: cord-297684-9q3oopaz authors: Dobaño, Carlota; Vidal, Marta; Santano, Rebeca; Jiménez, Alfons; Chi, Jordi; Barrios, Diana; Ruiz-Olalla, Gemma; Melero, Natalia Rodrigo; Carolis, Carlo; Parras, Daniel; Serra, Pau; de Aguirre, Paula Martínez; Carmona-Torre, Francisco; Reina, Gabriel; Santamaria, Pere; Mayor, Alfredo; García-Basteiro, Alberto; Izquierdo, Luis; Aguilar, Ruth; Moncunill, Gemma title: Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens date: 2020-06-12 journal: bioRxiv DOI: 10.1101/2020.06.11.147363 sha: doc_id: 297684 cord_uid: 9q3oopaz file: cache/cord-296268-kb7fgfaq.json key: cord-296268-kb7fgfaq authors: Mendonça, Luiza; Howe, Andrew; Gilchrist, James B.; Sun, Dapeng; Knight, Michael L.; Zanetti-Domingues, Laura C.; Bateman, Benji; Krebs, Anna-Sophia; Chen, Long; Radecke, Julika; Sheng, Yuewen; Li, Vivian D.; Ni, Tao; Kounatidis, Ilias; Koronfel, Mohamed A.; Szynkiewicz, Marta; Harkiolaki, Maria; Martin-Fernandez, Marisa L.; James, William; Zhang, Peijun title: SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.05.370239 sha: doc_id: 296268 cord_uid: kb7fgfaq file: cache/cord-296981-tded20ih.json key: cord-296981-tded20ih authors: Gilmore, Kerry; Zhou, Yuyong; Ramirez, Santseharay; Pham, Long V.; Fahnøe, Ulrik; Feng, Shan; Offersgaard, Anna; Trimpert, Jakob; Bukh, Jens; Osterrieder, Klaus; Gottwein, Judith M.; Seeberger, Peter H. title: In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2 date: 2020-10-05 journal: bioRxiv DOI: 10.1101/2020.10.05.326637 sha: doc_id: 296981 cord_uid: tded20ih file: cache/cord-296007-1gsgd22t.json key: cord-296007-1gsgd22t authors: Mohseni, Amir Hossein; Taghinezhad-S, Sedigheh; Su, Bing; Wang, Feng title: Inferring MHC interacting SARS-CoV-2 epitopes recognized by TCRs towards designing T cell-based vaccines date: 2020-09-12 journal: bioRxiv DOI: 10.1101/2020.09.12.294413 sha: doc_id: 296007 cord_uid: 1gsgd22t file: cache/cord-296237-i9cti2ok.json key: cord-296237-i9cti2ok authors: Díez, José-María; Romero, Carolina; Vergara-Alert, Júlia; Belló-Perez, Melissa; Rodon, Jordi; Honrubia, José Manuel; Segalés, Joaquim; Sola, Isabel; Enjuanes, Luis; Gajardo, Rodrigo title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.19.160879 sha: doc_id: 296237 cord_uid: i9cti2ok file: cache/cord-297826-2nruf2g7.json key: cord-297826-2nruf2g7 authors: Tian, Jing-Hui; Patel, Nita; Haupt, Robert; Zhou, Haixia; Weston, Stuart; Hammond, Holly; Lague, James; Portnoff, Alyse D.; Norton, James; Guebre-Xabier, Mimi; Zhou, Bin; Jacobson, Kelsey; Maciejewski, Sonia; Khatoon, Rafia; Wisniewska, Malgorzata; Moffitt, Will; Kluepfel-Stahl, Stefanie; Ekechukwu, Betty; Papin, James; Boddapati, Sarathi; Wong, C. Jason; Piedra, Pedro A.; Frieman, Matthew B.; Massare, Michael J.; Fries, Louis; Lövgren Bengtsson, Karin; Stertman, Linda; Ellingsworth, Larry; Glenn, Gregory; Smith, Gale title: SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.06.29.178509 sha: doc_id: 297826 cord_uid: 2nruf2g7 file: cache/cord-297747-kifqgskc.json key: cord-297747-kifqgskc authors: Lupala, Cecylia S.; Li, Xuanxuan; Lei, Jian; Chen, Hong; Qi, Jianxun; Liu, Haiguang; Su, Xiao-dong title: Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein date: 2020-03-27 journal: bioRxiv DOI: 10.1101/2020.03.24.005561 sha: doc_id: 297747 cord_uid: kifqgskc file: cache/cord-298716-pubhq564.json key: cord-298716-pubhq564 authors: Bryche, Bertrand; St Albin, Audrey; Murri, Severine; Lacôte, Sandra; Pulido, Coralie; Gouilh, Meriadeg Ar; Lesellier, Sandrine; Servat, Alexandre; Wasniewski, Marine; Picard-Meyer, Evelyne; Monchatre-Leroy, Elodie; Volmer, Romain; Rampin, Olivier; Le Goffic, Ronan; Marianneau, Philippe; Meunier, Nicolas title: Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.16.151704 sha: doc_id: 298716 cord_uid: pubhq564 file: cache/cord-295765-c7o2ukm6.json key: cord-295765-c7o2ukm6 authors: Silvas, Jesus A.; Jureka, Alexander S.; Nicolini, Anthony M.; Chvatal, Stacie A.; Basler, Christopher F. title: Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication date: 2020-07-20 journal: bioRxiv DOI: 10.1101/2020.07.18.210211 sha: doc_id: 295765 cord_uid: c7o2ukm6 file: cache/cord-294275-pp0vlaye.json key: cord-294275-pp0vlaye authors: Li, Jingjing; Quan, Weipeng; Yan, Shuge; Wu, Shuangju; Qin, Jianhu; Yang, Tingting; Liang, Fan; Wang, Depeng; Liang, Yu title: Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow date: 2020-06-03 journal: bioRxiv DOI: 10.1101/2020.06.03.131474 sha: doc_id: 294275 cord_uid: pp0vlaye file: cache/cord-295257-iguhy1z8.json key: cord-295257-iguhy1z8 authors: Calcagnile, Matteo; Forgez, Patricia; Iannelli, Antonio; Bucci, Cecilia; Alifano, Marco; Alifano, Pietro title: ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study date: 2020-04-24 journal: bioRxiv DOI: 10.1101/2020.04.23.057042 sha: doc_id: 295257 cord_uid: iguhy1z8 file: cache/cord-298321-8871aifz.json key: cord-298321-8871aifz authors: Laamarti, Meriem; Kartti, Souad; Alouane, Tarek; Laamarti, Rokia; Allam, Loubna; Ouadghiri, Mouna; Chemao-Elfihri, M.W.; Smyej, Imane; Rahoui, Jalila; Benrahma, Houda; Diawara, Idrissa; Essabbar, Abdelomunim; Boumajdi, Nasma; Bendani, Houda; Bouricha, El Mehdi; Aanniz, Tarik; Elattar, Jalil; Hafidi, Naima EL; Jaoudi, Rachid EL; Sbabou, Laila; Nejjari, Chakib; Amzazi, Saaid; Mentag, Rachid; Belyamani, Lahcen; Ibrahimi, Azeddine title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.06.30.181123 sha: doc_id: 298321 cord_uid: 8871aifz file: cache/cord-298326-f5q7j3iu.json key: cord-298326-f5q7j3iu authors: Nick, Benjamin C.; Pandya, Mansi C.; Lu, Xiaotao; Franke, Megan E.; Callahan, Sean M.; Hasik, Emily F.; Berthrong, Sean T.; Denison, Mark R.; Stobart, Christopher C. title: Identification of a critical horseshoe-shaped region in the nsp5 (Mpro, 3CLpro) protease interdomain loop (IDL) of coronavirus mouse hepatitis virus (MHV) date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.18.160671 sha: doc_id: 298326 cord_uid: f5q7j3iu file: cache/cord-299737-r34d0rx7.json key: cord-299737-r34d0rx7 authors: Grant, Paul R; Turner, Melanie A; Shin, Gee Yen; Nastouli, Eleni; Levett, Lisa J title: Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic date: 2020-04-08 journal: bioRxiv DOI: 10.1101/2020.04.06.028316 sha: doc_id: 299737 cord_uid: r34d0rx7 file: cache/cord-296649-h6oyjz56.json key: cord-296649-h6oyjz56 authors: Scherf-Clavel, Oliver; Kaczmarek, Edith; Kinzig, Martina; Friedl, Bettina; Feja, Malte; Höhl, Rainer; Nau, Roland; Holzgrabe, Ulrike; Gernert, Manuela; Richter, Franziska; Sörgel, Fritz title: Tissue Level Profiling of SARS-CoV-2 antivirals in mice to predict their effects: comparing Remdesivir’s active metabolite GS-441 524 vs. the clinically failed Hydroxychloroquine date: 2020-11-06 journal: bioRxiv DOI: 10.1101/2020.09.16.299537 sha: doc_id: 296649 cord_uid: h6oyjz56 file: cache/cord-297786-jz1d1m2e.json key: cord-297786-jz1d1m2e authors: Hasan, Md. Mahbub; Das, Rasel; Rasheduzzaman, Md.; Hussain, Md Hamed; Muzahid, Nazmul Hasan; Salauddin, Asma; Rumi, Meheadi Hasan; Rashid, S M Mahbubur; Siddiki, AMAM Zonaed; Mannan, Adnan title: Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date: 2020-08-26 journal: bioRxiv DOI: 10.1101/2020.08.25.267658 sha: doc_id: 297786 cord_uid: jz1d1m2e file: cache/cord-300423-q2i328sz.json key: cord-300423-q2i328sz authors: Bai, Lei; Zhao, Yongliang; Dong, Jiazhen; Liang, Simeng; Guo, Ming; Liu, Xinjin; Wang, Xin; Huang, Zhixiang; Sun, Xiaoyi; Zhang, Zhen; Dong, Lianghui; Liu, Qianyun; Zheng, Yucheng; Niu, Danping; Xiang, Min; Song, Kun; Ye, Jiajie; Zheng, Wenchao; Tang, Zhidong; Tang, Mingliang; Zhou, Yu; Shen, Chao; Dai, Ming; Zhou, Li; Chen, Yu; Yan, Huan; Lan, Ke; Xu, Ke title: Co-infection of influenza A virus enhances SARS-CoV-2 infectivity date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.14.335893 sha: doc_id: 300423 cord_uid: q2i328sz file: cache/cord-297044-tpp40j0g.json key: cord-297044-tpp40j0g authors: Jin, Zhenming; Zhao, Yao; Sun, Yuan; Zhang, Bing; Wang, Haofeng; Wu, Yan; Zhu, Yan; Zhu, Chen; Hu, Tianyu; Du, Xiaoyu; Duan, Yinkai; Yu, Jing; Yang, Xiaobao; Yang, Xiuna; Yang, Kailin; Liu, Xiang; Guddat, Luke W.; Xiao, Gengfu; Zhang, Leike; Yang, Haitao; Rao, Zihe title: Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur date: 2020-04-28 journal: bioRxiv DOI: 10.1101/2020.04.09.033233 sha: doc_id: 297044 cord_uid: tpp40j0g file: cache/cord-300783-pvn2qq0f.json key: cord-300783-pvn2qq0f authors: Sadykov, Mukhtar; Mourier, Tobias; Guan, Qingtian; Pain, Arnab title: Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction date: 2020-08-07 journal: bioRxiv DOI: 10.1101/2020.06.19.161687 sha: doc_id: 300783 cord_uid: pvn2qq0f file: cache/cord-301535-eui41zyg.json key: cord-301535-eui41zyg authors: Chandler-Brown, Devon; Bueno, Anna M.; Atay, Oguzhan; Tsao, David S. title: A Highly Scalable and Rapidly Deployable RNA Extraction-Free COVID-19 Assay by Quantitative Sanger Sequencing date: 2020-04-10 journal: bioRxiv DOI: 10.1101/2020.04.07.029199 sha: doc_id: 301535 cord_uid: eui41zyg file: cache/cord-300194-nsp53lv6.json key: cord-300194-nsp53lv6 authors: Rath, Soumya Lipsa; Kumar, Kishant title: Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.10.145086 sha: doc_id: 300194 cord_uid: nsp53lv6 file: cache/cord-300707-k9uk14b3.json key: cord-300707-k9uk14b3 authors: Bouwman, Kim M.; Tomris, Ilhan; Turner, Hannah L.; van der Woude, Roosmarijn; Bosman, Gerlof P.; Rockx, Barry; Herfst, Sander; Haagmans, Bart L.; Ward, Andrew B.; Boons, Geert-Jan; de Vries, Robert P. title: Multimerization- and glycosylation-dependent receptor binding of SARS-CoV-2 spike proteins date: 2020-09-04 journal: bioRxiv DOI: 10.1101/2020.09.04.282558 sha: doc_id: 300707 cord_uid: k9uk14b3 file: cache/cord-301233-nenw0f81.json key: cord-301233-nenw0f81 authors: Naydenova, Katerina; Muir, Kyle W.; Wu, Long-Fei; Zhang, Ziguo; Coscia, Francesca; Peet, Mathew J.; Castro-Hartmann, Pablo; Qian, Pu; Sader, Kasim; Dent, Kyle; Kimanius, Dari; Sutherland, John D.; Löwe, Jan; Barford, David; Russo, Christopher J. title: Structural basis for the inhibition of the SARS-CoV-2 RNA-dependent RNA polymerase by favipiravir-RTP date: 2020-10-21 journal: bioRxiv DOI: 10.1101/2020.10.21.347690 sha: doc_id: 301233 cord_uid: nenw0f81 file: cache/cord-298242-iuskpoug.json key: cord-298242-iuskpoug authors: Yu, Alvin; Pak, Alexander J.; He, Peng; Monje-Galvan, Viviana; Casalino, Lorenzo; Gaieb, Zied; Dommer, Abigail C.; Amaro, Rommie E.; Voth, Gregory A. title: A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion date: 2020-10-02 journal: bioRxiv DOI: 10.1101/2020.10.02.323915 sha: doc_id: 298242 cord_uid: iuskpoug file: cache/cord-300078-svu06v9c.json key: cord-300078-svu06v9c authors: Haghani, Milad; Bliemer, Michiel C. J. title: Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCov literature date: 2020-06-01 journal: bioRxiv DOI: 10.1101/2020.05.31.126813 sha: doc_id: 300078 cord_uid: svu06v9c file: cache/cord-302146-51hof7it.json key: cord-302146-51hof7it authors: Cross, Thomas J.; Takahashi, Gemma R.; Diessner, Elizabeth M.; Crosby, Marquise G.; Farahmand, Vesta; Zhuang, Shannon; Butts, Carter T.; Martin, Rachel W. title: Sequence characterization and molecular modeling of clinically relevant variants of the SARS-CoV-2 main protease date: 2020-05-15 journal: bioRxiv DOI: 10.1101/2020.05.15.097493 sha: doc_id: 302146 cord_uid: 51hof7it file: cache/cord-304544-tqtdjh2m.json key: cord-304544-tqtdjh2m authors: Enes, Ak; Pir, Pınar title: Transcriptional response of signalling pathways to SARS-CoV-2 infection in normal human bronchial epithelial cells date: 2020-06-20 journal: bioRxiv DOI: 10.1101/2020.06.20.163006 sha: doc_id: 304544 cord_uid: tqtdjh2m file: cache/cord-302608-fw4pmaoc.json key: cord-302608-fw4pmaoc authors: Huang, Jiao-Mei; Jan, Syed Sajid; Wei, Xiaobin; Wan, Yi; Ouyang, Songying title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date: 2020-03-19 journal: bioRxiv DOI: 10.1101/2020.03.16.993816 sha: doc_id: 302608 cord_uid: fw4pmaoc file: cache/cord-303069-ss6g3jkg.json key: cord-303069-ss6g3jkg authors: Jakhar, Renu; Gakhar, S.K title: An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2 date: 2020-05-26 journal: bioRxiv DOI: 10.1101/2020.05.26.115790 sha: doc_id: 303069 cord_uid: ss6g3jkg file: cache/cord-302733-rfuyd041.json key: cord-302733-rfuyd041 authors: Dellicour, Simon; Durkin, Keith; Hong, Samuel L.; Vanmechelen, Bert; Martí-Carreras, Joan; Gill, Mandev S.; Meex, Cécile; Bontems, Sébastien; André, Emmanuel; Gilbert, Marius; Walker, Conor; De Maio, Nicola; Faria, Nuno R.; Hadfield, James; Hayette, Marie-Pierre; Bours, Vincent; Wawina-Bokalanga, Tony; Artesi, Maria; Baele, Guy; Maes, Piet title: A phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages date: 2020-10-21 journal: bioRxiv DOI: 10.1101/2020.05.05.078758 sha: doc_id: 302733 cord_uid: rfuyd041 file: cache/cord-305589-ofpna4k1.json key: cord-305589-ofpna4k1 authors: Schubert, Katharina; Karousis, Evangelos D.; Jomaa, Ahmad; Scaiola, Alain; Echeverria, Blanca; Gurzeler, Lukas-Adrian; Leibundgut, Marc; Thiel, Volker; Mühlemann, Oliver; Ban, Nenad title: SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation date: 2020-07-07 journal: bioRxiv DOI: 10.1101/2020.07.07.191676 sha: doc_id: 305589 cord_uid: ofpna4k1 file: cache/cord-298172-iyxyennq.json key: cord-298172-iyxyennq authors: Guo, Youjia; Kawaguchi, Atsushi; Takeshita, Masaru; Sekiya, Takeshi; Hirohama, Mikako; Yamashita, Akio; Siomi, Haruhiko; Murano, Kensaku title: Potent mouse monoclonal antibodies that block SARS-CoV-2 infection date: 2020-10-02 journal: bioRxiv DOI: 10.1101/2020.10.01.323220 sha: doc_id: 298172 cord_uid: iyxyennq file: cache/cord-303832-1kcqhgjw.json key: cord-303832-1kcqhgjw authors: Dai, Manman; Li, Huanan; Yan, Nan; Huang, Jinyu; Zhao, Li; Xu, Siqi; Jiang, Shibo; Pan, Chungen; Liao, Ming title: Long-term survival of salmon-attached SARS-CoV-2 at 4°C as a potential source of transmission in seafood markets date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.06.284695 sha: doc_id: 303832 cord_uid: 1kcqhgjw file: cache/cord-304792-8sdxqmkb.json key: cord-304792-8sdxqmkb authors: Khan, Md. Abdullah-Al-Kamran; Islam, Abul Bashar Mir Md. Khademul title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date: 2020-05-08 journal: bioRxiv DOI: 10.1101/2020.05.06.050260 sha: doc_id: 304792 cord_uid: 8sdxqmkb file: cache/cord-300272-95o8yd7h.json key: cord-300272-95o8yd7h authors: Thépaut, Michel; Luczkowiak, Joanna; Vivès, Corinne; Labiod, Nuria; Bally, Isabelle; Lasala, Fátima; Grimoire, Yasmina; Fenel, Daphna; Sattin, Sara; Thielens, Nicole; Schoehn, Guy; Bernardi, Anna; Delgado, Rafael; Fieschi, Franck title: DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist date: 2020-08-10 journal: bioRxiv DOI: 10.1101/2020.08.09.242917 sha: doc_id: 300272 cord_uid: 95o8yd7h file: cache/cord-303399-s1hbpvn7.json key: cord-303399-s1hbpvn7 authors: Straus, Marco R.; Kinder, Jonathan T.; Segall, Michal; Dutch, Rebecca Ellis; Whittaker, Gary R. title: SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses date: 2019-08-31 journal: bioRxiv DOI: 10.1101/752592 sha: doc_id: 303399 cord_uid: s1hbpvn7 file: cache/cord-303868-aes92l6s.json key: cord-303868-aes92l6s authors: Steffen, Tara L.; Stone, E. Taylor; Hassert, Mariah; Geerling, Elizabeth; Grimberg, Brian T.; Espino, Ana M.; Pantoja, Petraleigh; Climent, Consuelo; Hoft, Daniel F.; George, Sarah L.; Sariol, Carlos A.; Pinto, Amelia K.; Brien, James D. title: The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera date: 2020-08-22 journal: bioRxiv DOI: 10.1101/2020.08.21.261727 sha: doc_id: 303868 cord_uid: aes92l6s file: cache/cord-305054-4d84b2g6.json key: cord-305054-4d84b2g6 authors: Liu, Yuan; Yan, Changhui title: The selection of reference genome and the search for the origin of SARS-CoV-2 date: 2020-08-11 journal: bioRxiv DOI: 10.1101/2020.08.10.245290 sha: doc_id: 305054 cord_uid: 4d84b2g6 file: cache/cord-307536-qeo5dfxg.json key: cord-307536-qeo5dfxg authors: Feng, Ye; Qiu, Min; Liu, Liang; Zou, Shengmei; Li, Yun; Luo, Kai; Guo, Qianpeng; Han, Ning; Sun, Yingqiang; Wang, Kui; Zhuang, Xinlei; Zhang, Shanshan; Chen, Shuqing; Mo, Fan title: Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.03.03.962332 sha: doc_id: 307536 cord_uid: qeo5dfxg file: cache/cord-300847-ycuiso0g.json key: cord-300847-ycuiso0g authors: Li, Wei; Drelich, Aleksandra; Martinez, David R.; Gralinski, Lisa; Chen, Chuan; Sun, Zehua; Schäfer, Alexandra; Leist, Sarah R.; Liu, Xianglei; Zhelev, Doncho; Zhang, Liyong; Peterson, Eric C.; Conard, Alex; Mellors, John W.; Tseng, Chien-Te; Baric, Ralph S.; Dimitrov, Dimiter S. title: Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models date: 2020-06-02 journal: bioRxiv DOI: 10.1101/2020.05.13.093088 sha: doc_id: 300847 cord_uid: ycuiso0g file: cache/cord-305496-t8ykkekl.json key: cord-305496-t8ykkekl authors: Stone, E. Taylor; Geerling, Elizabeth; Steffen, Tara L.; Hassert, Mariah; Dickson, Alexandria; Spencer, Jacqueline F.; Toth, Karoly; DiPaolo, Richard J.; Brien, James D.; Pinto, Amelia K. title: Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay date: 2020-08-21 journal: bioRxiv DOI: 10.1101/2020.08.20.259838 sha: doc_id: 305496 cord_uid: t8ykkekl file: cache/cord-308310-wtmjt3hf.json key: cord-308310-wtmjt3hf authors: Zha, Lisha; Zhao, Hongxin; Mohsen, Mona O.; Hong, Liang; Zhou, Yuhang; Li, Zehua; Yao, Chuankai; Guo, Lijie; Chen, Hongquan; Liu, Xuelan; Chang, Xinyue; Zhang, Jie; Li, Dong; Wu, Ke; Vogel, Monique; Bachmann, Martin F; Wang, Junfeng title: Development of a COVID-19 vaccine based on the receptor binding domain displayed on virus-like particles date: 2020-05-14 journal: bioRxiv DOI: 10.1101/2020.05.06.079830 sha: doc_id: 308310 cord_uid: wtmjt3hf file: cache/cord-307504-cogk5kig.json key: cord-307504-cogk5kig authors: Zhu, Yuanmei; Yu, Danwei; Yan, Hongxia; Chong, Huihui; He, Yuxian title: Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity date: 2020-03-28 journal: bioRxiv DOI: 10.1101/2020.03.26.009233 sha: doc_id: 307504 cord_uid: cogk5kig file: cache/cord-310752-zl2g9wqo.json key: cord-310752-zl2g9wqo authors: Sato, Taku; Ueha, Rumi; Goto, Takao; Yamauchi, Akihito; Kondo, Kenji; Yamasoba, Tatsuya title: Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats date: 2020-05-15 journal: bioRxiv DOI: 10.1101/2020.05.14.097204 sha: doc_id: 310752 cord_uid: zl2g9wqo file: cache/cord-302160-4yfvspaq.json key: cord-302160-4yfvspaq authors: Ruetalo, Natalia; Businger, Ramona; Schindler, Michael title: Rapid and efficient inactivation of surface dried SARS-CoV-2 by UV-C irradiation date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.09.22.308098 sha: doc_id: 302160 cord_uid: 4yfvspaq file: cache/cord-307242-e20gtx0z.json key: cord-307242-e20gtx0z authors: Jegouic, Sophie M.; Loureiro, Silvia; Thom, Michelle; Paliwal, Deepa; Jones, Ian M. title: Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.21.109298 sha: doc_id: 307242 cord_uid: e20gtx0z file: cache/cord-307811-6e3j0pn7.json key: cord-307811-6e3j0pn7 authors: Hao, Wei; Ma, Bo; Li, Ziheng; Wang, Xiaoyu; Gao, Xiaopan; Li, Yaohao; Qin, Bo; Shang, Shiying; Cui, Sheng; Tan, Zhongping title: Binding of the SARS-CoV-2 Spike Protein to Glycans date: 2020-07-02 journal: bioRxiv DOI: 10.1101/2020.05.17.100537 sha: doc_id: 307811 cord_uid: 6e3j0pn7 file: cache/cord-306901-uuwgpuhw.json key: cord-306901-uuwgpuhw authors: Roy, Sylvie; Ghani, Karim; de Campos-Lima, Pedro O.; Caruso, Manuel title: Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein date: 2020-09-16 journal: bioRxiv DOI: 10.1101/2020.09.16.298992 sha: doc_id: 306901 cord_uid: uuwgpuhw file: cache/cord-307701-fujejfwb.json key: cord-307701-fujejfwb authors: Gaurav, Shubham; Pandey, Shambhavi; Puvar, Apurvasinh; Shah, Tejas; Joshi, Madhvi; Joshi, Chaitanya; Kumar, Sachin title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date: 2020-06-07 journal: bioRxiv DOI: 10.1101/2020.06.06.137604 sha: doc_id: 307701 cord_uid: fujejfwb file: cache/cord-309289-vm0k7hfx.json key: cord-309289-vm0k7hfx authors: Rothan, Hussin A.; Stone, Shannon; Natekar, Janhavi; Kumari, Pratima; Arora, Komal; Kumar, Mukesh title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.14.041228 sha: doc_id: 309289 cord_uid: vm0k7hfx file: cache/cord-311240-o0zyt2vb.json key: cord-311240-o0zyt2vb authors: Motayo, Babatunde Olarenwaju; Oluwasemowo, Olukunle Oluwapamilerin; Akinduti, Paul Akiniyi; Olusola, Babatunde Adebiyi; Aerege, Olumide T; Faneye, Adedayo Omotayo title: Evolution and Genetic Diversity of SARSCoV-2 in Africa Using Whole Genome Sequences date: 2020-07-27 journal: bioRxiv DOI: 10.1101/2020.07.27.222901 sha: doc_id: 311240 cord_uid: o0zyt2vb file: cache/cord-310464-lkdkdque.json key: cord-310464-lkdkdque authors: Rayko, Mikhail; Komissarov, Aleksey title: Quality control of low-frequency variants in SARS-CoV-2 genomes date: 2020-05-07 journal: bioRxiv DOI: 10.1101/2020.04.26.062422 sha: doc_id: 310464 cord_uid: lkdkdque file: cache/cord-304356-jyp9gjh9.json key: cord-304356-jyp9gjh9 authors: Grant, Rogan A.; Morales-Nebreda, Luisa; Markov, Nikolay S.; Swaminathan, Suchitra; Guzman, Estefany R.; Abbott, Darryl A.; Donnelly, Helen K.; Donayre, Alvaro; Goldberg, Isaac A.; Klug, Zasu M.; Borkowski, Nicole; Lu, Ziyan; Kihshen, Hermon; Politanska, Yuliya; Sichizya, Lango; Kang, Mengjia; Shilatifard, Ali; Qi, Chao; Argento, A. Christine; Kruser, Jacqueline M.; Malsin, Elizabeth S.; Pickens, Chiagozie O.; Smith, Sean; Walter, James M.; Pawlowski, Anna E.; Schneider, Daniel; Nannapaneni, Prasanth; Abdala-Valencia, Hiam; Bharat, Ankit; Gottardi, Cara J.; Budinger, GR Scott; Misharin, Alexander V.; Singer, Benjamin D.; Wunderink, Richard G. title: Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells date: 2020-08-05 journal: bioRxiv DOI: 10.1101/2020.08.05.238188 sha: doc_id: 304356 cord_uid: jyp9gjh9 file: cache/cord-311114-ggcpsjk8.json key: cord-311114-ggcpsjk8 authors: Radhakrishnan, Chandni; Divakar, Mohit Kumar; Jain, Abhinav; Viswanathan, Prasanth; Bhoyar, Rahul C.; Jolly, Bani; Imran, Mohamed; Sharma, Disha; Rophina, Mercy; Ranjan, Gyan; Jose, Beena Philomina; Raman, Rajendran Vadukkoot; Kesavan, Thulaseedharan Nallaveettil; George, Kalpana; Mathew, Sheela; Poovullathil, Jayesh Kumar; Govindan, Sajeeth Kumar Keeriyatt; Nair, Priyanka Raveendranadhan; Vadekkandiyil, Shameer; Gladson, Vineeth; Mohan, Midhun; Parambath, Fairoz Cheriyalingal; Mangla, Mohit; Shamnath, Afra; Sivasubbu, Sridhar; Scaria, Vinod title: Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date: 2020-09-09 journal: bioRxiv DOI: 10.1101/2020.09.09.289892 sha: doc_id: 311114 cord_uid: ggcpsjk8 file: cache/cord-312038-g76cpjp7.json key: cord-312038-g76cpjp7 authors: Brunaugh, Ashlee D.; Seo, Hyojong; Warnken, Zachary; Ding, Li; Seo, Sang Heui; Smyth, Hugh D.C. title: Broad-Spectrum, Patient-Adaptable Inhaled Niclosamide-Lysozyme Particles are Efficacious Against Coronaviruses in Lethal Murine Infection Models date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.09.24.310490 sha: doc_id: 312038 cord_uid: g76cpjp7 file: cache/cord-305858-gp1u4kh7.json key: cord-305858-gp1u4kh7 authors: Song, Xiang; Hu, Wei; Yu, Haibo; Zhao, Laura; Zhao, Yeqian; Zhao, Yong title: High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients date: 2020-07-19 journal: bioRxiv DOI: 10.1101/2020.07.18.210120 sha: doc_id: 305858 cord_uid: gp1u4kh7 file: cache/cord-310230-9wfb43gt.json key: cord-310230-9wfb43gt authors: Ghorbani, Mahdi; Brooks, Bernard R.; Klauda, Jeffery B. title: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations date: 2020-06-27 journal: bioRxiv DOI: 10.1101/2020.06.27.175448 sha: doc_id: 310230 cord_uid: 9wfb43gt file: cache/cord-302920-jkr438p9.json key: cord-302920-jkr438p9 authors: Gasser, Romain; Cloutier, Marc; Prévost, Jérémie; Fink, Corby; Ducas, Éric; Ding, Shilei; Dussault, Nathalie; Landry, Patricia; Tremblay, Tony; Laforce-Lavoie, Audrey; Lewin, Antoine; Beaudoin-Bussières, Guillaume; Laumaea, Annemarie; Medjahed, Halima; Larochelle, Catherine; Richard, Jonathan; Dekaban, Gregory A.; Dikeakos, Jimmy D.; Bazin, Renée; Finzi, Andrés title: Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 date: 2020-10-09 journal: bioRxiv DOI: 10.1101/2020.10.09.333278 sha: doc_id: 302920 cord_uid: jkr438p9 file: cache/cord-311214-eqwxkwqa.json key: cord-311214-eqwxkwqa authors: Kumar, Roshan; Verma, Helianthous; Singhvi, Nirjara; Sood, Utkarsh; Gupta, Vipin; Singh, Mona; Kumari, Rashmi; Hira, Princy; Nagar, Shekhar; Talwar, Chandni; Nayyar, Namita; Anand, Shailly; Rawat, Charu Dogra; Verma, Mansi; Negi, Ram Krishan; Singh, Yogendra; Lal, Rup title: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date: 2020-04-16 journal: bioRxiv DOI: 10.1101/2020.03.25.006213 sha: doc_id: 311214 cord_uid: eqwxkwqa file: cache/cord-311445-b6bc6vwd.json key: cord-311445-b6bc6vwd authors: Bansal, Kanika; Patil, Prabhu B. title: Codon pattern reveals SARS-CoV-2 to be a monomorphic strain that emerged through recombination of replicase and envelope alleles of bat and pangolin origin date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.10.12.335521 sha: doc_id: 311445 cord_uid: b6bc6vwd file: cache/cord-308428-zw26usmh.json key: cord-308428-zw26usmh authors: Walter, Justin D.; Hutter, Cedric A.J.; Garaeva, Alisa A.; Scherer, Melanie; Zimmermann, Iwan; Wyss, Marianne; Rheinberger, Jan; Ruedin, Yelena; Earp, Jennifer C.; Egloff, Pascal; Sorgenfrei, Michèle; Hürlimann, Lea M.; Gonda, Imre; Meier, Gianmarco; Remm, Sille; Thavarasah, Sujani; Zimmer, Gert; Slotboom, Dirk J.; Paulino, Cristina; Plattet, Philippe; Seeger, Markus A. title: Highly potent bispecific sybodies neutralize SARS-CoV-2 date: 2020-11-10 journal: bioRxiv DOI: 10.1101/2020.11.10.376822 sha: doc_id: 308428 cord_uid: zw26usmh file: cache/cord-310017-c8rd714a.json key: cord-310017-c8rd714a authors: Popa, Alexandra; Genger, Jakob-Wendelin; Nicholson, Michael; Penz, Thomas; Schmid, Daniela; Aberle, Stephan W.; Agerer, Benedikt; Lercher, Alexander; Endler, Lukas; Colaço, Henrique; Smyth, Mark; Schuster, Michael; Grau, Miguel; Martinez, Francisco; Pich, Oriol; Borena, Wegene; Pawelka, Erich; Keszei, Zsofia; Senekowitsch, Martin; Laine, Jan; Aberle, Judith H.; Redlberger-Fritz, Monika; Karolyi, Mario; Zoufaly, Alexander; Maritschnik, Sabine; Borkovec, Martin; Hufnagl, Peter; Nairz, Manfred; Weiss, Günter; Wolfinger, Michael T.; von Laer, Dorothee; Superti-Furga, Giulio; Lopez-Bigas, Nuria; Puchhammer-Stöckl, Elisabeth; Allerberger, Franz; Michor, Franziska; Bock, Christoph; Bergthaler, Andreas title: Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date: 2020-07-17 journal: bioRxiv DOI: 10.1101/2020.07.15.204339 sha: doc_id: 310017 cord_uid: c8rd714a file: cache/cord-312305-ll29frwc.json key: cord-312305-ll29frwc authors: Sun, Shihui; Gu, Hongjing; Cao, Lei; Chen, Qi; Yang, Guan; Li, Rui-Ting; Fan, Hang; Ye, Qing; Deng, Yong-Qiang; Song, Xiaopeng; Qi, Yini; Li, Min; Lan, Jun; Feng, Rui; Guo, Yan; Qin, Si; Wang, Lei; Zhang, Yi-Fei; Zhou, Chao; Zhao, Lingna; Chen, Yuehong; Shen, Meng; Cui, Yujun; Yang, Xiao; Wang, Xinquan; Wang, Hui; Wang, Xiangxi; Qin, Cheng-Feng title: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date: 2020-11-11 journal: bioRxiv DOI: 10.1101/2020.11.10.377333 sha: doc_id: 312305 cord_uid: ll29frwc file: cache/cord-312524-ee5xw1r8.json key: cord-312524-ee5xw1r8 authors: Moustafa, Ahmed M.; Planet, Paul J. title: Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread date: 2020-06-08 journal: bioRxiv DOI: 10.1101/2020.06.08.139055 sha: doc_id: 312524 cord_uid: ee5xw1r8 file: cache/cord-306924-dw35dlx3.json key: cord-306924-dw35dlx3 authors: Wohlers, Inken; Calonga-Solís, Verónica; Jobst, Jan-Niklas; Busch, Hauke title: COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans date: 2020-11-03 journal: bioRxiv DOI: 10.1101/2020.11.02.365551 sha: doc_id: 306924 cord_uid: dw35dlx3 file: cache/cord-312228-wbyqmvhs.json key: cord-312228-wbyqmvhs authors: Xiao, Minfeng; Liu, Xiaoqing; Ji, Jingkai; Li, Min; Li, Jiandong; Yang, Lin; Sun, Wanying; Ren, Peidi; Yang, Guifang; Zhao, Jincun; Liang, Tianzhu; Ren, Huahui; Chen, Tian; Zhong, Huanzi; Song, Wenchen; Wang, Yanqun; Deng, Ziqing; Zhao, Yanping; Ou, Zhihua; Wang, Daxi; Cai, Jielun; Cheng, Xinyi; Feng, Taiqing; Wu, Honglong; Gong, Yanping; Yang, Huanming; Wang, Jian; Xu, Xun; Zhu, Shida; Chen, Fang; Zhang, Yanyan; Chen, Weijun; Li, Yimin; Li, Junhua title: Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples date: 2020-03-19 journal: bioRxiv DOI: 10.1101/2020.03.16.993584 sha: doc_id: 312228 cord_uid: wbyqmvhs file: cache/cord-312473-7i7efdp2.json key: cord-312473-7i7efdp2 authors: Sidhom, John-William; Baras, Alexander S. title: Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope date: 2020-06-20 journal: bioRxiv DOI: 10.1101/2020.06.20.160499 sha: doc_id: 312473 cord_uid: 7i7efdp2 file: cache/cord-309411-2dfiwo65.json key: cord-309411-2dfiwo65 authors: Paris, Kristina A.; Santiago, Ulises; Camacho, Carlos J. title: Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology date: 2020-06-23 journal: bioRxiv DOI: 10.1101/2020.06.16.155457 sha: doc_id: 309411 cord_uid: 2dfiwo65 file: cache/cord-309512-d8n9711b.json key: cord-309512-d8n9711b authors: Bacus, Michael G.; Dayap, Stephen Adrian H.; Tampon, Nikki Vanesa T.; Udarbe, Marielle M.; Puentespina, Roberto P.; Villanueva, Sharon Yvette Angelina M.; de Cadiz, Aleyla E.; Achondo, Marion John Michael M.; Murao, Lyre Anni E. title: Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses date: 2020-05-05 journal: bioRxiv DOI: 10.1101/2020.05.04.076281 sha: doc_id: 309512 cord_uid: d8n9711b file: cache/cord-310477-vniokol0.json key: cord-310477-vniokol0 authors: Pontes, Camila; Ruiz-Serra, Victoria; Lepore, Rosalba; Valencia, Alfonso title: Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs date: 2020-08-21 journal: bioRxiv DOI: 10.1101/2020.08.21.260745 sha: doc_id: 310477 cord_uid: vniokol0 file: cache/cord-311843-un6urdb1.json key: cord-311843-un6urdb1 authors: Baray, Juwel Chandra; Khan, Md. Maksudur Rahman; Mahmud, Asif; Islam, Md. Jikrul; Myti, Sanat; Ali, Md. Rostum; Sarker, Md. Enamul Haq; Kumar, Samir; Chowdhury, Md. Mobarak Hossain; Roy, Rony; Islam, Faqrul; Barman, Uttam; Khan, Habiba; Chakraborty, Sourav; Hossain, Md. Manik; Chowdhury, Md. Mashfiqur Rahman; Ghosh, Polash; Mohiuddin, Mohammad; Sultana, Naznin; Nag, Kakon title: BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response date: 2020-09-30 journal: bioRxiv DOI: 10.1101/2020.09.29.319061 sha: doc_id: 311843 cord_uid: un6urdb1 file: cache/cord-311066-62edsbfc.json key: cord-311066-62edsbfc authors: Cox, Brian J. title: Integration of viral transcriptome sequencing with structure and sequence motifs predicts novel regulatory elements in SARS-CoV-2 date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.06.24.169144 sha: doc_id: 311066 cord_uid: 62edsbfc file: cache/cord-312702-fruzsn26.json key: cord-312702-fruzsn26 authors: Finch, Courtney L.; Crozier, Ian; Lee, Ji Hyun; Byrum, Russ; Cooper, Timothy K.; Liang, Janie; Sharer, Kaleb; Solomon, Jeffrey; Sayre, Philip J.; Kocher, Gregory; Bartos, Christopher; Aiosa, Nina M.; Castro, Marcelo; Larson, Peter A.; Adams, Ricky; Beitzel, Brett; Di Paola, Nicholas; Kugelman, Jeffrey R.; Kurtz, Jonathan R.; Burdette, Tracey; Nason, Martha C.; Feuerstein, Irwin M.; Palacios, Gustavo; Claire, Marisa C. St.; Lackemeyer, Matthew G.; Johnson, Reed F.; Braun, Katarina M.; Ramuta, Mitchell D.; Wada, Jiro; Schmaljohn, Connie S.; Friedrich, Thomas C.; O’Connor, David H.; Kuhn, Jens H. title: Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) date: 2020-05-14 journal: bioRxiv DOI: 10.1101/2020.05.14.096727 sha: doc_id: 312702 cord_uid: fruzsn26 file: cache/cord-313571-umcbulcw.json key: cord-313571-umcbulcw authors: Martínez-Murcia, Antonio; Bru, Gema; Navarro, Aaron; Ros-Tárraga, Patricia; García-Sirera, Adrián; Pérez, Laura title: In silico design and validation of commercial kit GPS™ CoVID-19 dtec-RT-qPCR Test under criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012 date: 2020-05-05 journal: bioRxiv DOI: 10.1101/2020.04.27.065383 sha: doc_id: 313571 cord_uid: umcbulcw file: cache/cord-314072-av3r7it7.json key: cord-314072-av3r7it7 authors: Liu, Zhuoming; VanBlargan, Laura A.; Rothlauf, Paul W.; Bloyet, Louis-Marie; Chen, Rita E.; Stumpf, Spencer; Zhao, Haiyan; Errico, John M.; Theel, Elitza S.; Ellebedy, Ali H.; Fremont, Daved H.; Diamond, Michael S.; Whelan, Sean P. J. title: Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization date: 2020-11-08 journal: bioRxiv DOI: 10.1101/2020.11.06.372037 sha: doc_id: 314072 cord_uid: av3r7it7 file: cache/cord-313247-55loucvc.json key: cord-313247-55loucvc authors: Pipes, Lenore; Wang, Hongru; Huelsenbeck, John P.; Nielsen, Rasmus title: Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.06.19.160630 sha: doc_id: 313247 cord_uid: 55loucvc file: cache/cord-309556-xv3413k1.json key: cord-309556-xv3413k1 authors: Chow, Ryan D.; Chen, Sidi title: The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date: 2020-04-15 journal: bioRxiv DOI: 10.1101/2020.04.07.030684 sha: doc_id: 309556 cord_uid: xv3413k1 file: cache/cord-311333-shvtfxog.json key: cord-311333-shvtfxog authors: Fukumoto, Tatsuya; Iwasaki, Sumio; Fujisawa, Shinichi; Hayasaka, Kasumi; Sato, Kaori; Oguri, Satoshi; Taki, Keisuke; Nakakubo, Sho; Kamada, Keisuke; Yamashita, Yu; Konno, Satoshi; Nishida, Mutsumi; Sugita, Junichi; Teshima, Takanori title: Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification date: 2020-05-28 journal: bioRxiv DOI: 10.1101/2020.05.27.120410 sha: doc_id: 311333 cord_uid: shvtfxog file: cache/cord-312414-g5px0b65.json key: cord-312414-g5px0b65 authors: Takagi, Akira; Matsui, Masanori title: An immunodominance hierarchy exists in CD8+ T cell responses to HLA-A*02:01-restricted epitopes identified from the non-structural polyprotein 1a of SARS-CoV-2 date: 2020-09-19 journal: bioRxiv DOI: 10.1101/2020.09.18.304493 sha: doc_id: 312414 cord_uid: g5px0b65 file: cache/cord-312999-3erodkv9.json key: cord-312999-3erodkv9 authors: Hassan, Sk. Sarif; Attrish, Diksha; Ghosh, Shinjini; Choudhury, Pabitra Pal; Uversky, Vladimir N.; Uhal, Bruce D.; Lundstrom, Kenneth; Rezaei, Nima; Aljabali, Alaa A. A.; Seyran, Murat; Pizzol, Damiano; Adadi, Parise; Abd El-Aziz, Tarek Mohamed; Soares, Antonio; Kandimalla, Ramesh; Tambuwala, Murtaza; Lal, Amos; Azad, Gajendra Kumar; Sherchan, Samendra P.; Baetas-da-Cruz, Wagner; Palù, Giorgio; Brufsky, Adam M. title: Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2 date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.06.284976 sha: doc_id: 312999 cord_uid: 3erodkv9 file: cache/cord-314321-klb8oe9q.json key: cord-314321-klb8oe9q authors: Chen, Serena H.; Young, M. Todd; Gounley, John; Stanley, Christopher; Bhowmik, Debsindhu title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date: 2020-04-18 journal: bioRxiv DOI: 10.1101/2020.04.17.047548 sha: doc_id: 314321 cord_uid: klb8oe9q file: cache/cord-314445-4cb4a9r5.json key: cord-314445-4cb4a9r5 authors: McNamara, Ryan P.; Caro-Vegas, Carolina; Landis, Justin T.; Moorad, Razia; Pluta, Linda J.; Eason, Anthony B.; Thompson, Cecilia; Bailey, Aubrey; Villamor, Femi Cleola S.; Lange, Philip T.; Wong, Jason P.; Seltzer, Tischan; Seltzer, Jedediah; Zhou, Yijun; Vahrson, Wolfgang; Juarez, Angelica; Meyo, James O.; Calabre, Tiphaine; Broussard, Grant; Rivera-Soto, Ricardo; Chappell, Danielle L.; Baric, Ralph S.; Damania, Blossom; Miller, Melissa B.; Dittmer, Dirk P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.19.161141 sha: doc_id: 314445 cord_uid: 4cb4a9r5 file: cache/cord-313805-6mnclfeg.json key: cord-313805-6mnclfeg authors: Suzuki, Yuichiro J.; Nikolaienko, Sofia I.; Dibrova, Vyacheslav A.; Dibrova, Yulia V.; Vasylyk, Volodymyr M.; Novikov, Mykhailo Y.; Shults, Nataliia V.; Gychka, Sergiy G. title: SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.10.12.335083 sha: doc_id: 313805 cord_uid: 6mnclfeg file: cache/cord-315702-pn8247j2.json key: cord-315702-pn8247j2 authors: Sahakijpijarn, Sawittree; Moon, Chaeho; Koleng, John J.; Christensen, Dale J.; Williams, Robert O. title: Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing date: 2020-09-22 journal: bioRxiv DOI: 10.1101/2020.07.26.222109 sha: doc_id: 315702 cord_uid: pn8247j2 file: cache/cord-313795-jr3n3uo9.json key: cord-313795-jr3n3uo9 authors: McAuley, Julie L.; Deerain, Joshua M.; Hammersla, William; Aktepe, Turgut E.; Purcell, Damian J.F.; Mackenzie, Jason M. title: Liquid chalk is an antiseptic against SARS-CoV-2 and influenza A respiratory viruses date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.11.02.364661 sha: doc_id: 313795 cord_uid: jr3n3uo9 file: cache/cord-317523-idji1l0a.json key: cord-317523-idji1l0a authors: Xu, Huanzhou; Chitre, Siddhi A.; Akinyemi, Ibukun A.; Loeb, Julia C.; Lednicky, John A.; McIntosh, Michael T.; Bhaduri-McIntosh, Sumita title: SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway date: 2020-10-27 journal: bioRxiv DOI: 10.1101/2020.10.27.357731 sha: doc_id: 317523 cord_uid: idji1l0a file: cache/cord-314329-rzda8x62.json key: cord-314329-rzda8x62 authors: Wells, Stephen A. title: Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure date: 2020-03-12 journal: bioRxiv DOI: 10.1101/2020.03.10.986190 sha: doc_id: 314329 cord_uid: rzda8x62 file: cache/cord-313215-diqfmitr.json key: cord-313215-diqfmitr authors: Luo, Lei; Liu, Dan; Zhang, Hao; Li, Zhihao; Zhen, Ruonan; Zhang, Xiru; Xie, Huaping; Song, Weiqi; Liu, Jie; Huang, Qingmei; Liu, Jingwen; Yang, Xingfen; Chen, Zongqiu; Mao, Chen title: Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases date: 2020-07-09 journal: bioRxiv DOI: 10.1101/2020.07.09.195008 sha: doc_id: 313215 cord_uid: diqfmitr file: cache/cord-313505-2lr4xara.json key: cord-313505-2lr4xara authors: Resende, Paola Cristina; Delatorre, Edson; Gräf, Tiago; Mir, Daiana; Motta, Fernando do Couto; Appolinario, Luciana Reis; da Paixão, Anna Carolina Dias; Ogrzewalska, Maria; Caetano, Braulia; dos Santos, Mirleide Cordeiro; de Almeida Ferreira, Jessylene; Santos Junior, Edivaldo Costa; da Silva, Sandro Patroca; Fernandes, Sandra Bianchini; Vianna, Lucas A; da Costa Souza, Larissa; Ferro, Jean F G; Nardy, Vanessa B; Croda, Júlio; Oliveira, Wanderson K; Abreu, André; Bello, Gonzalo; Siqueira, Marilda M title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date: 2020-06-18 journal: bioRxiv DOI: 10.1101/2020.06.17.158006 sha: doc_id: 313505 cord_uid: 2lr4xara file: cache/cord-320054-wqpr8v3p.json key: cord-320054-wqpr8v3p authors: Yuan, Xianlin; li, liangping title: The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes date: 2020-08-24 journal: bioRxiv DOI: 10.1101/2020.08.24.264895 sha: doc_id: 320054 cord_uid: wqpr8v3p file: cache/cord-320490-3jmo35jc.json key: cord-320490-3jmo35jc authors: Ismail, Saba; Ahmad, Sajjad; Azam, Syed Sikander title: Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine date: 2020-04-12 journal: bioRxiv DOI: 10.1101/2020.04.05.026005 sha: doc_id: 320490 cord_uid: 3jmo35jc file: cache/cord-315982-iuez41zj.json key: cord-315982-iuez41zj authors: Achdout, Hagit; Aimon, Anthony; Bar-David, Elad; Barr, Haim; Ben-Shmuel, Amir; Bennett, James; Bobby, Melissa L; Brun, Juliane; Sarma, BVNBS; Calmiano, Mark; Carbery, Anna; Cattermole, Emma; Chodera, John D.; Clyde, Austin; Coffland, Joseph E.; Cohen, Galit; Cole, Jason; Contini, Alessandro; Cox, Lisa; Cvitkovic, Milan; Dias, Alex; Douangamath, Alice; Duberstein, Shirly; Dudgeon, Tim; Dunnett, Louise; Eastman, Peter K.; Erez, Noam; Fairhead, Michael; Fearon, Daren; Fedorov, Oleg; Ferla, Matteo; Foster, Holly; Foster, Richard; Gabizon, Ronen; Gehrtz, Paul; Gileadi, Carina; Giroud, Charline; Glass, William G.; Glen, Robert; Glinert, Itai; Gorichko, Marian; Gorrie-Stone, Tyler; Griffen, Edward J; Heer, Jag; Hill, Michelle; Horrell, Sam; Hurley, Matthew F.D.; Israely, Tomer; Jajack, Andrew; Jnoff, Eric; John, Tobias; Kantsadi, Anastassia L.; Kenny, Peter W.; Kiappes, John L.; Koekemoer, Lizbe; Kovar, Boris; Krojer, Tobias; Lee, Alpha Albert; Lefker, Bruce A.; Levy, Haim; London, Nir; Lukacik, Petra; Macdonald, Hannah Bruce; MacLean, Beth; Malla, Tika R.; Matviiuk, Tatiana; McCorkindale, Willam; Melamed, Sharon; Michurin, Oleg; Mikolajek, Halina; Morris, Aaron; Morris, Garrett M.; Morwitzer, Melody Jane; Moustakas, Demetri; Neto, Jose Brandao; Oleinikovas, Vladas; Overheul, Gijs J.; Owen, David; Pai, Ruby; Pan, Jin; Paran, Nir; Perry, Benjamin; Pingle, Maneesh; Pinjari, Jakir; Politi, Boaz; Powell, Ailsa; Psenak, Vladimir; Puni, Reut; Rangel, Victor L.; Reddi, Rambabu N.; Reid, St Patrick; Resnick, Efrat; Robinson, Matthew C.; Robinson, Ralph P.; Rufa, Dominic; Schofield, Christopher; Shaikh, Aarif; Shi, Jiye; Shurrush, Khriesto; Sittner, Assa; Skyner, Rachael; Smalley, Adam; Smilova, Mihaela D.; Spencer, John; Strain-Damerell, Claire; Swamy, Vishwanath; Tamir, Hadas; Tennant, Rachael; Thompson, Andrew; Thompson, Warren; Tomasio, Susana; Tumber, Anthony; Vakonakis, Ioannis; van Rij, Ronald P.; Varghese, Finny S.; Vaschetto, Mariana; Vitner, Einat B.; Voelz, Vincent; von Delft, Annette; von Delft, Frank; Walsh, Martin; Ward, Walter; Weatherall, Charlie; Weiss, Shay; Wild, Conor Francis; Wittmann, Matthew; Wright, Nathan; Yahalom-Ronen, Yfat; Zaidmann, Daniel; Zidane, Hadeer; Zitzmann, Nicole title: COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning date: 2020-10-30 journal: bioRxiv DOI: 10.1101/2020.10.29.339317 sha: doc_id: 315982 cord_uid: iuez41zj file: cache/cord-317628-1inxq7t5.json key: cord-317628-1inxq7t5 authors: Cuccarese, Michael F.; Earnshaw, Berton A.; Heiser, Katie; Fogelson, Ben; Davis, Chadwick T.; McLean, Peter F.; Gordon, Hannah B.; Skelly, Kathleen-Rose; Weathersby, Fiona L.; Rodic, Vlad; Quigley, Ian K.; Pastuzyn, Elissa D.; Mendivil, Brandon M.; Lazar, Nathan H.; Brooks, Carl A.; Carpenter, Joseph; Probst, Brandon L.; Jacobson, Pamela; Glazier, Seth W.; Ford, Jes; Jensen, James D.; Campbell, Nicholas D.; Statnick, Michael A.; Low, Adeline S.; Thomas, Kirk R.; Carpenter, Anne E.; Hegde, Sharath S.; Alfa, Ronald W.; Victors, Mason L.; Haque, Imran S.; Chong, Yolanda T.; Gibson, Christopher C. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 journal: bioRxiv DOI: 10.1101/2020.08.02.233064 sha: doc_id: 317628 cord_uid: 1inxq7t5 file: cache/cord-319447-xanewi59.json key: cord-319447-xanewi59 authors: Sun, Jiya; Ye, Fei; Wu, Aiping; Yang, Ren; Pan, Mei; Sheng, Jie; Zhu, Wenjie; Mao, Longfei; Wang, Ming; Huang, Baoying; Tan, Wenjie; Jiang, Taijiao title: Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.04.30.071274 sha: doc_id: 319447 cord_uid: xanewi59 file: cache/cord-313910-bwe2f7xf.json key: cord-313910-bwe2f7xf authors: Bojadzic, Damir; Alcazar, Oscar; Chen, Jinshui; Buchwald, Peter title: Small-Molecule In Vitro Inhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 date: 2020-10-22 journal: bioRxiv DOI: 10.1101/2020.10.22.351056 sha: doc_id: 313910 cord_uid: bwe2f7xf file: cache/cord-315760-9g8901v6.json key: cord-315760-9g8901v6 authors: Teng, Xufei; Li, Qianpeng; Li, Zhao; Zhang, Yuansheng; Niu, Guangyi; Xiao, Jingfa; Yu, Jun; Zhang, Zhang; Song, Shuhui title: Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades date: 2020-08-30 journal: bioRxiv DOI: 10.1101/2020.08.26.267781 sha: doc_id: 315760 cord_uid: 9g8901v6 file: cache/cord-320417-01l27d99.json key: cord-320417-01l27d99 authors: Wang, Hai-Long title: The emergence of inter-clade hybrid SARS-CoV-2 lineages revealed by 2D nucleotide variation mapping date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.13.338038 sha: doc_id: 320417 cord_uid: 01l27d99 file: cache/cord-321050-yabt72jf.json key: cord-321050-yabt72jf authors: Tuttle, Kathryn D.; Minter, Ross; Waugh, Katherine A.; Araya, Paula; Ludwig, Michael; Sempeck, Colin; Smith, Keith; Andrysik, Zdenek; Burchill, Matthew A.; Tamburini, Beth A.J.; Orlicky, David J.; Sullivan, Kelly D.; Espinosa, Joaquin M. title: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date: 2020-04-09 journal: bioRxiv DOI: 10.1101/2020.04.07.024455 sha: doc_id: 321050 cord_uid: yabt72jf file: cache/cord-318499-uihof6k6.json key: cord-318499-uihof6k6 authors: Beddingfield, Brandon; Iwanaga, Naoki; Zheng, Wenshu; Roy, Chad J.; Hu, Tony Y.; Kolls, Jay; Bix, Gregory title: The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.15.153387 sha: doc_id: 318499 cord_uid: uihof6k6 file: cache/cord-321049-9ozn6il7.json key: cord-321049-9ozn6il7 authors: de Almeida, Paula Rodrigues; Demoliner, Meriane; Antunes Eisen, Ana Karolina; Heldt, Fágner Henrique; Hansen, Alana Witt; Schallenberger, Karoline; Fleck, Juliane Deise; Spilki, Fernando Rosado title: SARS-CoV2 quantification using RT-dPCR: a faster and safer alternative to assist viral genomic copies assessment using RT-qPCR date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.05.01.072728 sha: doc_id: 321049 cord_uid: 9ozn6il7 file: cache/cord-317123-0tdfvlqd.json key: cord-317123-0tdfvlqd authors: Tan, Xiaotian; Lin, Cory; Zhang, Jie; Khaing Oo, Maung Kyaw; Fan, Xudong title: Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples date: 2020-04-21 journal: bioRxiv DOI: 10.1101/2020.04.20.052233 sha: doc_id: 317123 cord_uid: 0tdfvlqd file: cache/cord-321155-dty18esg.json key: cord-321155-dty18esg authors: Zhang, Rongxin; Ke, Xiao; Gu, Yu; Liu, Hongde; Sun, Xiao title: Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2 date: 2020-06-05 journal: bioRxiv DOI: 10.1101/2020.06.05.135749 sha: doc_id: 321155 cord_uid: dty18esg file: cache/cord-323041-wf0hlhim.json key: cord-323041-wf0hlhim authors: Larsen, Mads Delbo; de Graaf, Erik L.; Sonneveld, Myrthe E.; Plomp, H. Rosina; Linty, Federica; Visser, Remco; Brinkhaus, Maximilian; Šuštić, Tonći; de Taeye, Steven W.; Bentlage, Arthur E.H.; Nouta, Jan; Natunen, Suvi; Koeleman, Carolien A. M.; Sainio, Susanna; Kootstra, Neeltje A.; Brouwer, Philip J.M.; Sanders, Rogier W.; van Gils, Marit J.; de Bruin, Sanne; Vlaar, Alexander P.J.; Zaaijer, Hans L.; Wuhrer, Manfred; van der Schoot, C. Ellen; Vidarsson, Gestur title: Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19 date: 2020-05-18 journal: bioRxiv DOI: 10.1101/2020.05.18.099507 sha: doc_id: 323041 cord_uid: wf0hlhim file: cache/cord-318478-fn0gcxbb.json key: cord-318478-fn0gcxbb authors: Ziv, Omer; Price, Jonathan; Shalamova, Lyudmila; Kamenova, Tsveta; Goodfellow, Ian; Weber, Friedemann; Miska, Eric A. title: The short- and long-range RNA-RNA Interactome of SARS-CoV-2 date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.07.19.211110 sha: doc_id: 318478 cord_uid: fn0gcxbb file: cache/cord-319100-3gdawhfn.json key: cord-319100-3gdawhfn authors: Kirkland, P.D.; Frost, M.J. title: The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2 and other viruses date: 2020-06-10 journal: bioRxiv DOI: 10.1101/2020.06.09.142323 sha: doc_id: 319100 cord_uid: 3gdawhfn file: cache/cord-321027-64y43o0y.json key: cord-321027-64y43o0y authors: Andreano, Emanuele; Nicastri, Emanuele; Paciello, Ida; Pileri, Piero; Manganaro, Noemi; Piccini, Giulia; Manenti, Alessandro; Pantano, Elisa; Kabanova, Anna; Troisi, Marco; Vacca, Fabiola; Cardamone, Dario; De Santi, Concetta; Agrati, Chiara; Capobianchi, Maria Rosaria; Castilletti, Concetta; Emiliozzi, Arianna; Fabbiani, Massimiliano; Montagnani, Francesca; Montomoli, Emanuele; Sala, Claudia; Ippolito, Giuseppe; Rappuoli, Rino title: Identification of neutralizing human monoclonal antibodies from Italian Covid-19 convalescent patients date: 2020-05-09 journal: bioRxiv DOI: 10.1101/2020.05.05.078154 sha: doc_id: 321027 cord_uid: 64y43o0y file: cache/cord-322942-y4zd2oui.json key: cord-322942-y4zd2oui authors: Olagnier, David; Farahani, Ensieh; Thyrsted, Jacob; Cadanet, Julia B.; Herengt, Angela; Idorn, Manja; Hait, Alon; Hernaez, Bruno; Knudsen, Alice; Iversen, Marie Beck; Schilling, Mirjam; Jørgensen, Sofie E.; Thomsen, Michelle; Reinert, Line; Lappe, Michael; Hoang, Huy-Dung; Gilchrist, Victoria H.; Hansen, Anne Louise; Ottosen, Rasmus; Gunderstofte, Camilla; Møller, Charlotte; van der Horst, Demi; Peri, Suraj; Balachandran, Siddarth; Huang, Jinrong; Jakobsen, Martin; Svenningsen, Esben B.; Poulsen, Thomas B.; Bartsch, Lydia; Thielke, Anne L.; Luo, Yonglun; Alain, Tommy; Rehwinkel, Jan; Alcamí, Antonio; Hiscott, John; Mogensen, Trine; Paludan, Søren R.; Holm, Christian K. title: Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate date: 2020-07-17 journal: bioRxiv DOI: 10.1101/2020.07.16.206458 sha: doc_id: 322942 cord_uid: y4zd2oui file: cache/cord-318253-vp22xd8p.json key: cord-318253-vp22xd8p authors: Parisi, Ortensia Ilaria; Dattilo, Marco; Patitucci, Francesco; Malivindi, Rocco; Pezzi, Vincenzo; Perrotta, Ida; Ruffo, Mariarosa; Amone, Fabio; Puoci, Francesco title: “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers date: 2020-05-28 journal: bioRxiv DOI: 10.1101/2020.05.28.120709 sha: doc_id: 318253 cord_uid: vp22xd8p file: cache/cord-323828-ug2duzw1.json key: cord-323828-ug2duzw1 authors: Ni, Dongchun; Lau, Kelvin; Lehmann, Frank; Fränkl, Andri; Hacker, David; Pojer, Florence; Stahlberg, Henning title: Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.10.12.336016 sha: doc_id: 323828 cord_uid: ug2duzw1 file: cache/cord-323654-9nnjex9y.json key: cord-323654-9nnjex9y authors: Ramachandran, Ashwin; Huyke, Diego A.; Sharma, Eesha; Sahoo, Malaya K.; Banaei, Niaz; Pinsky, Benjamin A.; Santiago, Juan G. title: Electric-field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2 date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.21.109637 sha: doc_id: 323654 cord_uid: 9nnjex9y file: cache/cord-318444-sgm24q1i.json key: cord-318444-sgm24q1i authors: Walter, Justin D.; Hutter, Cedric A.J.; Zimmermann, Iwan; Wyss, Marianne; Earp, Jennifer; Egloff, Pascal; Sorgenfrei, Michèle; Hürlimann, Lea M.; Gonda, Imre; Meier, Gianmarco; Remm, Sille; Thavarasah, Sujani; Plattet, Philippe; Seeger, Markus A. title: Sybodies targeting the SARS-CoV-2 receptor-binding domain date: 2020-05-16 journal: bioRxiv DOI: 10.1101/2020.04.16.045419 sha: doc_id: 318444 cord_uid: sgm24q1i file: cache/cord-321166-nvphu1fm.json key: cord-321166-nvphu1fm authors: Thomson, Emma C.; Rosen, Laura E.; Shepherd, James G.; Spreafico, Roberto; da Silva Filipe, Ana; Wojcechowskyj, Jason A.; Davis, Chris; Piccoli, Luca; Pascall, David J.; Dillen, Josh; Lytras, Spyros; Czudnochowski, Nadine; Shah, Rajiv; Meury, Marcel; Jesudason, Natasha; De Marco, Anna; Li, Kathy; Bassi, Jessica; O’Toole, Aine; Pinto, Dora; Colquhoun, Rachel M.; Culap, Katja; Jackson, Ben; Zatta, Fabrizia; Rambaut, Andrew; Jaconi, Stefano; Sreenu, Vattipally B.; Nix, Jay; Jarrett, Ruth F.; Beltramello, Martina; Nomikou, Kyriaki; Pizzuto, Matteo; Tong, Lily; Cameroni, Elisabetta; Johnson, Natasha; Wickenhagen, Arthur; Ceschi, Alessandro; Mair, Daniel; Ferrari, Paolo; Smollett, Katherine; Sallusto, Federica; Carmichael, Stephen; Garzoni, Christian; Nichols, Jenna; Galli, Massimo; Hughes, Joseph; Riva, Agostino; Ho, Antonia; Semple, Malcolm G.; Openshaw, Peter J.M.; Baillie, J. Kenneth; Rihn, Suzannah J.; Lycett, Samantha J.; Virgin, Herbert W.; Telenti, Amalio; Corti, Davide; Robertson, David L.; Snell, Gyorgy title: The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date: 2020-11-05 journal: bioRxiv DOI: 10.1101/2020.11.04.355842 sha: doc_id: 321166 cord_uid: nvphu1fm file: cache/cord-323685-gjocoa60.json key: cord-323685-gjocoa60 authors: Tsai, Shang-Jui; Guo, Chenxu; Atai, Nadia A.; Gould, Stephen J. title: Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination date: 2020-11-06 journal: bioRxiv DOI: 10.1101/2020.11.06.371419 sha: doc_id: 323685 cord_uid: gjocoa60 file: cache/cord-325432-geb4esu5.json key: cord-325432-geb4esu5 authors: Bukreyeva, Natalya; Mantlo, Emily K.; Sattler, Rachel A.; Huang, Cheng; Paessler, Slobodan; Zeldis, Jerry title: The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro date: 2020-04-09 journal: bioRxiv DOI: 10.1101/2020.04.07.028589 sha: doc_id: 325432 cord_uid: geb4esu5 file: cache/cord-324251-wgtatr8v.json key: cord-324251-wgtatr8v authors: Joshi, Madhvi; Puvar, Apurvasinh; Kumar, Dinesh; Ansari, Afzal; Pandya, Maharshi; Raval, Janvi; Patel, Zarna; Trivedi, Pinal; Gandhi, Monika; Pandya, Labdhi; Patel, Komal; Savaliya, Nitin; Bagatharia, Snehal; Kumar, Sachin; Joshi, Chaitanya title: Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology date: 2020-07-13 journal: bioRxiv DOI: 10.1101/2020.07.10.197095 sha: doc_id: 324251 cord_uid: wgtatr8v file: cache/cord-322654-6nccarjn.json key: cord-322654-6nccarjn authors: Luzes, Rafael; Muzi-Filho, Humberto; Pereira-Acácio, Amaury; Crisóstomo, Thuany; Vieyra, Adalberto title: Angiotensin-(3–4) modulates angiotensin converting enzyme 2 (ACE2) downregulation in proximal tubule cells due to overweight and undernutrition: implications regarding the severity of renal lesions in Covid-19 infection date: 2020-06-29 journal: bioRxiv DOI: 10.1101/2020.06.29.178293 sha: doc_id: 322654 cord_uid: 6nccarjn file: cache/cord-322955-7dw32xby.json key: cord-322955-7dw32xby authors: Kathwate, Gunderao H title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date: 2020-06-12 journal: bioRxiv DOI: 10.1101/2020.06.03.131755 sha: doc_id: 322955 cord_uid: 7dw32xby file: cache/cord-321369-xzu2faol.json key: cord-321369-xzu2faol authors: Andreano, Emanuele; Nicastri, Emanuele; Paciello, Ida; Pileri, Piero; Manganaro, Noemi; Piccini, Giulia; Manenti, Alessandro; Pantano, Elisa; Kabanova, Anna; Troisi, Marco; Vacca, Fabiola; Cardamone, Dario; De Santi, Concetta; Benincasa, Linda; Agrati, Chiara; Capobianchi, Maria Rosaria; Castilletti, Concetta; Emiliozzi, Arianna; Fabbiani, Massimiliano; Montagnani, Francesca; Depau, Lorenzo; Brunetti, Jlenia; Bracci, Luisa; Montomoli, Emanuele; Sala, Claudia; Ippolito, Giuseppe; Rappuoli, Rino title: Extremely potent human monoclonal antibodies from convalescent Covid-19 patients date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.10.07.328302 sha: doc_id: 321369 cord_uid: xzu2faol file: cache/cord-321427-bwcpd6im.json key: cord-321427-bwcpd6im authors: Yee, Min; Cohen, E. David; Haak, Jeannie; Dylag, Andrew M.; O’Reilly, Michael A. title: Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice date: 2020-07-22 journal: bioRxiv DOI: 10.1101/2020.07.22.215962 sha: doc_id: 321427 cord_uid: bwcpd6im file: cache/cord-322885-ob5euspo.json key: cord-322885-ob5euspo authors: Durdagi, Serdar; Dag, Cagdas; Dogan, Berna; Yigin, Merve; Avsar, Timucin; Buyukdag, Cengizhan; Erol, Ismail; Ertem, Betul; Calis, Seyma; Yildirim, Gunseli; Orhan, Muge D.; Guven, Omur; Aksoydan, Busecan; Destan, Ebru; Sahin, Kader; Besler, Sabri O.; Oktay, Lalehan; Shafiei, Alaleh; Tolu, Ilayda; Ayan, Esra; Yuksel, Busra; Peksen, Ayse B.; Gocenler, Oktay; Yucel, Ali D.; Can, Ozgur; Ozabrahamyan, Serena; Olkan, Alpsu; Erdemoglu, Ece; Aksit, Fulya; Tanisali, Gokhan; Yefanov, Oleksandr M.; Barty, Anton; Tolstikova, Alexandra; Ketawala, Gihan K.; Botha, Sabine; Dao, E. Han; Hayes, Brandon; Liang, Mengning; Seaberg, Matthew H.; Hunter, Mark S.; Batyuk, Alex; Mariani, Valerio; Su, Zhen; Poitevin, Frederic; Yoon, Chun Hong; Kupitz, Christopher; Sierra, Raymond G.; Snell, Edward; DeMirci, Hasan title: Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing date: 2020-09-09 journal: bioRxiv DOI: 10.1101/2020.09.09.287987 sha: doc_id: 322885 cord_uid: ob5euspo file: cache/cord-324892-mg2dziuw.json key: cord-324892-mg2dziuw authors: Carneiro, João; Gomes, Catarina; Couto, Cátia; Pereira, Filipe title: CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2 date: 2020-06-12 journal: bioRxiv DOI: 10.1101/2020.04.19.048991 sha: doc_id: 324892 cord_uid: mg2dziuw file: cache/cord-324480-7u5lh4jx.json key: cord-324480-7u5lh4jx authors: Sharma, A.; Preece, B.; Swann, H; Fan, X.; McKenney, R.J.; Ori-McKenney, K.M.; Saffarian, S.; Vershinin, M.D. title: Structural stability of SARS-CoV-2 degrades with temperature date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.12.336818 sha: doc_id: 324480 cord_uid: 7u5lh4jx file: cache/cord-320165-1b6sycgv.json key: cord-320165-1b6sycgv authors: Guo, Qirui; Zhao, Yingchi; Li, Junhong; Liu, Jiangning; Guo, Xuefei; Zhang, Zeming; Cao, Lili; Luo, Yujie; Bao, Linlin; Wang, Xiao; Wei, Xuemei; Deng, Wei; Chen, Luoying; Zhu, Hua; Gao, Ran; Qin, Chuan; Wang, Xiangxi; You, Fuping title: Small molecules inhibit SARS-COV-2 induced aberrant inflammation and viral replication in mice by targeting S100A8/A9-TLR4 axis date: 2020-09-09 journal: bioRxiv DOI: 10.1101/2020.09.09.288704 sha: doc_id: 320165 cord_uid: 1b6sycgv file: cache/cord-323839-a4oejky0.json key: cord-323839-a4oejky0 authors: Sasaki, Michihito; Uemura, Kentaro; Sato, Akihiko; Toba, Shinsuke; Sanaki, Takao; Maenaka, Katsumi; Hall, William W.; Orba, Yasuko; Sawa, Hirofumi title: SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.08.28.271163 sha: doc_id: 323839 cord_uid: a4oejky0 file: cache/cord-325124-0hxan9rw.json key: cord-325124-0hxan9rw authors: Li, Chenyu; Debruyne, David N.; Spencer, Julia; Kapoor, Vidushi; Liu, Lily Y.; Zhou, Bo; Pandey, Utsav; Bootwalla, Moiz; Ostrow, Dejerianne; Maglinte, Dennis T; Ruble, David; Ryutov, Alex; Shen, Lishuang; Lee, Lucie; Feigelman, Rounak; Burdon, Grayson; Liu, Jeffrey; Oliva, Alejandra; Borcherding, Adam; Tan, Hongdong; Urban, Alexander E.; Gai, Xiaowu; Bard, Jennifer Dien; Liu, Guoying; Liu, Zhitong title: Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing date: 2020-05-18 journal: bioRxiv DOI: 10.1101/2020.03.12.988246 sha: doc_id: 325124 cord_uid: 0hxan9rw file: cache/cord-323908-8dgngwmw.json key: cord-323908-8dgngwmw authors: He, Zhesheng; Zhao, Wencong; Niu, Wenchao; Gao, Xuejiao; Gao, Xingfa; Gong, Yong; Gao, Xueyun title: Molecules inhibit the enzyme activity of 3-chymotrypsin-like cysteine protease of SARS-CoV-2 virus: the experimental and theory studies date: 2020-05-31 journal: bioRxiv DOI: 10.1101/2020.05.28.120642 sha: doc_id: 323908 cord_uid: 8dgngwmw file: cache/cord-324888-oak27okj.json key: cord-324888-oak27okj authors: Leng, Ling; Ma, Jie; Zhang, Leike; Li, Wei; Zhao, Lei; Zhu, Yunping; Wu, Zhihong; Cao, Ruiyuan; Zhong, Wu title: Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis date: 2020-04-18 journal: bioRxiv DOI: 10.1101/2020.04.16.045799 sha: doc_id: 324888 cord_uid: oak27okj file: cache/cord-325348-yi6yu5l1.json key: cord-325348-yi6yu5l1 authors: Zhang, G.; Pomplun, S.; Loftis, A. R.; Tan, X.; Loas, A.; Pentelute, B. L. title: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD date: 2020-06-17 journal: bioRxiv DOI: 10.1101/2020.03.19.999318 sha: doc_id: 325348 cord_uid: yi6yu5l1 file: cache/cord-326282-uxn64olw.json key: cord-326282-uxn64olw authors: Lu, Maolin; Uchil, Pradeep D.; Li, Wenwei; Zheng, Desheng; Terry, Daniel S.; Gorman, Jason; Shi, Wei; Zhang, Baoshan; Zhou, Tongqing; Ding, Shilei; Gasser, Romain; Prévost, Jérémie; Beaudoin-Bussières, Guillaume; Anand, Sai Priya; Laumaea, Annemarie; Grover, Jonathan R.; Liu, Lihong; Ho, David D.; Mascola, John R.; Finzi, Andrés; Kwong, Peter D.; Blanchard, Scott C.; Mothes, Walther title: Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles date: 2020-09-13 journal: bioRxiv DOI: 10.1101/2020.09.10.286948 sha: doc_id: 326282 cord_uid: uxn64olw file: cache/cord-326337-s0fp5z1q.json key: cord-326337-s0fp5z1q authors: Chan, Kui K.; Tan, Timothy J.C.; Narayanan, Krishna K.; Procko, Erik title: An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants date: 2020-10-19 journal: bioRxiv DOI: 10.1101/2020.10.18.344622 sha: doc_id: 326337 cord_uid: s0fp5z1q file: cache/cord-327520-qj7coqfr.json key: cord-327520-qj7coqfr authors: Wei, Yulong; Silke, Jordan R.; Aris, Parisa; Xia, Xuhua title: Coronavirus genomes carry the signatures of their habitats date: 2020-06-13 journal: bioRxiv DOI: 10.1101/2020.06.13.149591 sha: doc_id: 327520 cord_uid: qj7coqfr file: cache/cord-326380-9ecsp66y.json key: cord-326380-9ecsp66y authors: Griesemer, Sara B; Van Slyke, Greta; St. George, Kirsten title: Assessment of sample pooling for clinical SARS-CoV-2 testing date: 2020-05-27 journal: bioRxiv DOI: 10.1101/2020.05.26.118133 sha: doc_id: 326380 cord_uid: 9ecsp66y file: cache/cord-325610-n3zb36am.json key: cord-325610-n3zb36am authors: Postlethwait, John H.; Farnsworth, Dylan R.; Miller, Adam C. title: An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities date: 2020-09-02 journal: bioRxiv DOI: 10.1101/2020.09.01.278366 sha: doc_id: 325610 cord_uid: n3zb36am file: cache/cord-324344-dxuabscn.json key: cord-324344-dxuabscn authors: Zhao, Xuesen; Zheng, Shuangli; Chen, Danying; Zheng, Mei; Li, Xinglin; Li, Guoli; Lin, Hanxin; Chang, Jinhong; Zeng, Hui; Guo, Ju-Tao title: LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2 date: 2020-04-05 journal: bioRxiv DOI: 10.1101/2020.04.02.021469 sha: doc_id: 324344 cord_uid: dxuabscn file: cache/cord-326866-nbd4arhx.json key: cord-326866-nbd4arhx authors: Fox, Charles W. title: The representation of women as authors of submissions to ecology journals during the COVID-19 pandemic date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.29.123455 sha: doc_id: 326866 cord_uid: nbd4arhx file: cache/cord-325420-e9fjo7tl.json key: cord-325420-e9fjo7tl authors: Xiao, Xia; Wang, Conghui; Chang, De; Wang, Ying; Dong, Xiaojing; Jiao, Tao; Zhao, Zhendong; Ren, Lili; Dela Cruz, Charles S; Sharma, Lokesh; Lei, Xiaobo; Wang, Jianwei title: Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2 date: 2020-07-06 journal: bioRxiv DOI: 10.1101/2020.07.06.188953 sha: doc_id: 325420 cord_uid: e9fjo7tl file: cache/cord-327711-welf0eb1.json key: cord-327711-welf0eb1 authors: Zhou, Daming; Duyvesteyn, Helen ME; Chen, Cheng-Pin; Huang, Chung-Guei; Chen, Ting-Hua; Shih, Shin-Ru; Lin, Yi-Chun; Cheng, Chien-Yu; Cheng, Shu-Hsing; Huang, Yhu-Chering; Lin, Tzou-Yien; Ma, Che; Huo, Jiandong; Carrique, Loic; Malinauskas, Tomas; Ruza, Reinis R; Shah, Pranav NM; Tan, Tiong Kit; Rijal, Pramila; Donat, Robert F.; Godwin, Kerry; Buttigieg, Karen; Tree, Julia; Radecke, Julika; Paterson, Neil G; Supasa, Piyasa; Mongkolsapaya, Juthathip; Screaton, Gavin R; Carroll, Miles W.; Jaramillo, Javier G.; Knight, Michael; James, William; Owens, Raymond J; Naismith, James H.; Townsend, Alain; Fry, Elizabeth E; Zhao, Yuguang; Ren, Jingshan; Stuart, David I; Huang, Kuan-Ying A. title: Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient date: 2020-06-13 journal: bioRxiv DOI: 10.1101/2020.06.12.148387 sha: doc_id: 327711 cord_uid: welf0eb1 file: cache/cord-328636-1q71gjwt.json key: cord-328636-1q71gjwt authors: Arora, Kajal; Rastogi, Ruchir; Arora, Nupur Mehrotra; Parashar, Deepak; Paliwal, Jeny; Naqvi, Aelia; Srivastava, Apoorva; Singh, Sudhir Kumar; Kalyanaraman, Sriganesh; Potdar, Swaroop; Kumar, Devanand; Arya, Vidya Bhushan; Bansal, Sarthi; Rautray, Satabdi; Singh, Indrajeet; Fengade, Pankaj Surendra; Kumar, Bibekanand; Kundu, Prabuddha Kumar title: Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate date: 2020-05-19 journal: bioRxiv DOI: 10.1101/2020.05.18.099234 sha: doc_id: 328636 cord_uid: 1q71gjwt file: cache/cord-325473-hrdanbn1.json key: cord-325473-hrdanbn1 authors: Ghahremanpour, Mohammad M.; Tirado-Rives, Julian; Deshmukh, Maya; Ippolito, Joseph A.; Zhang, Chun-Hui; de Vaca, Israel Cabeza; Liosi, Maria-Elena; Anderson, Karen S.; Jorgensen, William L. title: Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2 date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.08.28.271957 sha: doc_id: 325473 cord_uid: hrdanbn1 file: cache/cord-328073-bqeffvzl.json key: cord-328073-bqeffvzl authors: Limonta, Daniel; Dyna-Dagman, Lovely; Branton, William; Makio, Tadashi; Wozniak, Richard W.; Power, Christopher; Hobman, Tom C. title: Nodosome inhibition as a novel broad-spectrum antiviral strategy against arboviruses and SARS-CoV-2 date: 2020-11-06 journal: bioRxiv DOI: 10.1101/2020.11.05.370767 sha: doc_id: 328073 cord_uid: bqeffvzl file: cache/cord-326736-jd6fvaop.json key: cord-326736-jd6fvaop authors: Bosco-Lauth, Angela M.; Hartwig, Airn E.; Porter, Stephanie M.; Gordy, Paul W.; Nehring, Mary; Byas, Alex D.; VandeWoude, Sue; Ragan, Izabela K.; Maison, Rachel M.; Bowen, Richard A. title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.28.120998 sha: doc_id: 326736 cord_uid: jd6fvaop file: cache/cord-328257-kl4wh2zg.json key: cord-328257-kl4wh2zg authors: Xu, H; Zhang, XY; Wang, WW; Wang, JS title: Hydroxychloroquine increased psychiatric-like behaviors and disrupted the expression of related genes in the mouse brain date: 2020-09-28 journal: bioRxiv DOI: 10.1101/2020.09.27.316158 sha: doc_id: 328257 cord_uid: kl4wh2zg file: cache/cord-323967-2mo915u1.json key: cord-323967-2mo915u1 authors: Miersch, Shane; Li, Zhijie; Saberianfar, Reza; Ustav, Mart; Blazer, Levi; Chen, Chao; Ye, Wei; Pavlenco, Alia; Subramania, Suryasree; Singh, Serena; Ploder, Lynda; Ganaie, Safder; Leung, Daisy; Chen, Rita E.; Case, James Brett; Novelli, Guiseppe; Matusali, Giulia; Colavita, Francesca; Copabianchi, Maria R.; Jain, Suresh; Gupta, J.B.; Amarasinghe, Gaya; Diamond, Michael; Rini, James; Sidhu, Sachdev S. title: Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations date: 2020-11-01 journal: bioRxiv DOI: 10.1101/2020.10.31.362848 sha: doc_id: 323967 cord_uid: 2mo915u1 file: cache/cord-328189-jpkxjn6e.json key: cord-328189-jpkxjn6e authors: Brielle, Esther S.; Schneidman-Duhovny, Dina; Linial, Michal title: The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor date: 2020-03-12 journal: bioRxiv DOI: 10.1101/2020.03.10.986398 sha: doc_id: 328189 cord_uid: jpkxjn6e file: cache/cord-326257-rcv8sh22.json key: cord-326257-rcv8sh22 authors: Simmonds, P. title: Rampant C->U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses – causes and consequences for their short and long evolutionary trajectories date: 2020-05-01 journal: bioRxiv DOI: 10.1101/2020.05.01.072330 sha: doc_id: 326257 cord_uid: rcv8sh22 file: cache/cord-326666-melz5fq4.json key: cord-326666-melz5fq4 authors: Sun, Weitao title: The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe date: 2020-09-03 journal: bioRxiv DOI: 10.1101/2020.09.03.280727 sha: doc_id: 326666 cord_uid: melz5fq4 file: cache/cord-329240-atisrhas.json key: cord-329240-atisrhas authors: Fedorenko, Aliza; Grinberg, Maor; Orevi, Tomer; Kashtan, Nadav title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.15.152983 sha: doc_id: 329240 cord_uid: atisrhas file: cache/cord-328960-46zui1sl.json key: cord-328960-46zui1sl authors: Hillen, Hauke S.; Kokic, Goran; Farnung, Lucas; Dienemann, Christian; Tegunov, Dimitry; Cramer, Patrick title: Structure of replicating SARS-CoV-2 polymerase date: 2020-04-27 journal: bioRxiv DOI: 10.1101/2020.04.27.063180 sha: doc_id: 328960 cord_uid: 46zui1sl file: cache/cord-327431-dnppshnv.json key: cord-327431-dnppshnv authors: Hognon, Cécilia; Miclot, Tom; Iriepa, Cristina Garcia; Francés-Monerris, Antonio; Grandemange, Stephanie; Terenzi, Alessio; Marazzi, Marco; Barone, Giampaolo; Monari, Antonio title: Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses date: 2020-05-27 journal: bioRxiv DOI: 10.1101/2020.04.07.029447 sha: doc_id: 327431 cord_uid: dnppshnv file: cache/cord-326882-bbn1tfq5.json key: cord-326882-bbn1tfq5 authors: Li, Quan; Cao, Zanxia; Rahman, Proton title: Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations date: 2020-04-14 journal: bioRxiv DOI: 10.1101/2020.04.14.041434 sha: doc_id: 326882 cord_uid: bbn1tfq5 file: cache/cord-327808-k3jec87p.json key: cord-327808-k3jec87p authors: Zhu, Yunkai; Feng, Fei; Hu, Gaowei; Wang, Yuyan; Yu, Yin; Zhu, Yuanfei; Xu, Wei; Cai, Xia; Sun, Zhiping; Han, Wendong; Ye, Rong; Chen, Hongjun; Ding, Qiang; Cai, Qiliang; Qu, Di; Xie, Youhua; Yuan, Zhenghong; Zhang, Rong title: The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission date: 2020-08-25 journal: bioRxiv DOI: 10.1101/2020.08.25.266775 sha: doc_id: 327808 cord_uid: k3jec87p file: cache/cord-326441-w8iyh59u.json key: cord-326441-w8iyh59u authors: Bhattacharjee, Sayan; Bhattacharyya, Rajanya; Sengupta, Jayati title: Transmission of allosteric response within the homotrimer of SARS-CoV-2 spike upon recognition of ACE2 receptor by the receptor-binding domain date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.06.284901 sha: doc_id: 326441 cord_uid: w8iyh59u file: cache/cord-330031-c1n994j6.json key: cord-330031-c1n994j6 authors: Kratzel, Annika; Todt, Daniel; V’kovski, Philip; Steiner, Silvio; Gultom, Mitra L.; Thao, Tran Thi Nhu; Ebert, Nadine; Holwerda, Melle; Steinmann, Jörg; Niemeyer, Daniela; Dijkman, Ronald; Kampf, Günter; Drosten, Christian; Steinmann, Eike; Thiel, Volker; Pfaender, Stephanie title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols date: 2020-03-17 journal: bioRxiv DOI: 10.1101/2020.03.10.986711 sha: doc_id: 330031 cord_uid: c1n994j6 file: cache/cord-330473-f03ka7bd.json key: cord-330473-f03ka7bd authors: Yuan, Meng; Wu, Nicholas C.; Zhu, Xueyong; Lee, Chang-Chun D.; So, Ray T. Y.; Lv, Huibin; Mok, Chris K. P.; Wilson, Ian A. title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV date: 2020-03-14 journal: bioRxiv DOI: 10.1101/2020.03.13.991570 sha: doc_id: 330473 cord_uid: f03ka7bd file: cache/cord-331611-pwj226j0.json key: cord-331611-pwj226j0 authors: Shrimp, Jonathan H.; Kales, Stephen C.; Sanderson, Philip E.; Simeonov, Anton; Shen, Min; Hall, Matthew D. title: An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19 date: 2020-06-23 journal: bioRxiv DOI: 10.1101/2020.06.23.167544 sha: doc_id: 331611 cord_uid: pwj226j0 file: cache/cord-328585-1rkrrx8a.json key: cord-328585-1rkrrx8a authors: Lu, Shuai; Xie, Xi-xiu; Zhao, Lei; Wang, Bin; Zhu, Jie; Yang, Ting-rui; Yang, Guang-wen; Ji, Mei; Lv, Cui-ping; Xue, Jian; Dai, Er-hei; Fu, Xi-ming; Liu, Dong-qun; zhang, Lun; Hou, Sheng-jie; Yu, Xiao-lin; Wang, Yu-ling; Gao, Hui-xia; Shi, Xue-han; Ke, Chang-wen; Ke, Bi-xia; Jiang, Chun-guo; Liu, Rui-tian title: The immunodominant and neutralization linear epitopes for SARS-CoV-2 date: 2020-08-27 journal: bioRxiv DOI: 10.1101/2020.08.27.267716 sha: doc_id: 328585 cord_uid: 1rkrrx8a file: cache/cord-328695-nptfd6c2.json key: cord-328695-nptfd6c2 authors: Tengs, Torstein; Delwiche, Charles F.; Jonassen, Christine Monceyron title: A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species date: 2020-06-29 journal: bioRxiv DOI: 10.1101/2020.06.29.177030 sha: doc_id: 328695 cord_uid: nptfd6c2 file: cache/cord-330213-reb9vo7x.json key: cord-330213-reb9vo7x authors: Miladi, Milad; Fuchs, Jonas; Maier, Wolfgang; Weigang, Sebastian; Pedrosa, Núria Díaz i; Weiss, Lisa; Lother, Achim; Nekrutenko, Anton; Ruzsics, Zsolt; Panning, Marcus; Kochs, Georg; Gilsbach, Ralf; Grüning, Björn title: The landscape of SARS-CoV-2 RNA modifications date: 2020-07-18 journal: bioRxiv DOI: 10.1101/2020.07.18.204362 sha: doc_id: 330213 cord_uid: reb9vo7x file: cache/cord-330384-yujbcwg5.json key: cord-330384-yujbcwg5 authors: Al-Mulla, Fahd; Mohammad, Anwar; Al Madhoun, Ashraf; Haddad, Dania; Ali, Hamad; Eaaswarkhanth, Muthukrishnan; John, Sumi Elsa; Nizam, Rasheeba; Channanath, Arshad; Abu-Farha, Mohamed; Ahmad, Rasheed; Abubaker, Jehad; Thanaraj, Thangavel Alphonse title: A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine date: 2020-05-16 journal: bioRxiv DOI: 10.1101/2020.05.16.099176 sha: doc_id: 330384 cord_uid: yujbcwg5 file: cache/cord-328187-9zd79gai.json key: cord-328187-9zd79gai authors: Zhang, Yali; Wang, Shaojuan; Wu, Yangtao; Hou, Wangheng; Yuan, Lunzhi; Sheng, Chenguang; Wang, Juan; Ye, Jianghui; Zheng, Qingbing; Ma, Jian; Xu, Jingjing; Wei, Min; Li, Zonglin; Nian, Sheng; Xiong, Hualong; Zhang, Liang; Shi, Yang; Fu, Baorong; Cao, Jiali; Yang, Chuanlai; Li, Zhiyong; Yang, Ting; Liu, Lei; Yu, Hai; Hu, Jianda; Ge, Shengxiang; Chen, Yixin; Zhang, Tianying; Zhang, Jun; Cheng, Tong; Yuan, Quan; Xia, Ningshao title: Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors date: 2020-07-22 journal: bioRxiv DOI: 10.1101/2020.07.22.215236 sha: doc_id: 328187 cord_uid: 9zd79gai file: cache/cord-329102-2y49kcwu.json key: cord-329102-2y49kcwu authors: Lan, Tammy C. T.; Allan, Matthew F.; Malsick, Lauren E.; Khandwala, Stuti; Nyeo, Sherry S. Y.; Bathe, Mark; Griffiths, Anthony; Rouskin, Silvi title: Structure of the full SARS-CoV-2 RNA genome in infected cells date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.06.29.178343 sha: doc_id: 329102 cord_uid: 2y49kcwu file: cache/cord-329118-0gq5yusk.json key: cord-329118-0gq5yusk authors: Xiang, Boyu; Hu, Xiangyu; Li, Haoxuan; Ma, Li; Zhou, Hao; Wei, Ling; Fan, Jue; Zheng, Ji title: ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway date: 2020-06-06 journal: bioRxiv DOI: 10.1101/2020.06.05.137380 sha: doc_id: 329118 cord_uid: 0gq5yusk file: cache/cord-332178-0xyrmk5a.json key: cord-332178-0xyrmk5a authors: Chadchan, Sangappa B.; Maurya, Vineet K.; Popli, Pooja; Kommagani, Ramakrishna title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization date: 2020-06-24 journal: bioRxiv DOI: 10.1101/2020.06.23.168252 sha: doc_id: 332178 cord_uid: 0xyrmk5a file: cache/cord-328644-odtue60a.json key: cord-328644-odtue60a authors: Comandatore, Francesco; Chiodi, Alice; Gabrieli, Paolo; Biffignandi, Gherard Batisti; Perini, Matteo; Ricagno, Stefano; Mascolo, Elia; Petazzoni, Greta; Ramazzotti, Matteo; Rimoldi, Sara Giordana; Gismondo, Maria Rita; Micheli, Valeria; Sassera, Davide; Gaiarsa, Stefano; Bandi, Claudio; Brilli, Matteo title: Insurgence and worldwide diffusion of genomic variants in SARS-CoV-2 genomes date: 2020-05-28 journal: bioRxiv DOI: 10.1101/2020.04.30.071027 sha: doc_id: 328644 cord_uid: odtue60a file: cache/cord-331701-izkz1hz4.json key: cord-331701-izkz1hz4 authors: Eden, John-Sebastian; Rockett, Rebecca; Carter, Ian; Rahman, Hossinur; de Ligt, Joep; Hadfield, James; Storey, Matthew; Ren, Xiaoyun; Tulloch, Rachel; Basile, Kerri; Wells, Jessica; Byun, Roy; Gilroy, Nicky; O’Sullivan, Matthew V; Sintchenko, Vitali; Chen, Sharon C; Maddocks, Susan; Sorrell, Tania C; Holmes, Edward C; Dwyer, Dominic E; Kok, Jen title: An emergent clade of SARS-CoV-2 linked to returned travellers from Iran date: 2020-03-17 journal: bioRxiv DOI: 10.1101/2020.03.15.992818 sha: doc_id: 331701 cord_uid: izkz1hz4 file: cache/cord-327912-wfjdxgxh.json key: cord-327912-wfjdxgxh authors: Swann, Heather; Sharma, Abhimanyu; Preece, Benjamin; Peterson, Abby; Eldridge, Crystal; Belnap, David M.; Vershinin, Michael; Saffarian, Saveez title: Minimal system for assembly of SARS-CoV-2 virus like particles date: 2020-08-24 journal: bioRxiv DOI: 10.1101/2020.06.01.128058 sha: doc_id: 327912 cord_uid: wfjdxgxh file: cache/cord-332134-88wfcc3y.json key: cord-332134-88wfcc3y authors: Li, Tingting; Cai, Hongmin; Yao, Hebang; Zhou, Bingjie; Zhang, Ning; Gong, Yuhuan; Zhao, Yapei; Shen, Quan; Qin, Wenming; Hutter, Cedric A.J.; Lai, Yanling; Kuo, Shu-Ming; Bao, Juan; Lan, Jiaming; Seeger, Markus A.; Wong, Gary; Bi, Yuhai; Lavillette, Dimitri; Li, Dianfan title: A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection date: 2020-09-24 journal: bioRxiv DOI: 10.1101/2020.06.09.143438 sha: doc_id: 332134 cord_uid: 88wfcc3y file: cache/cord-332185-a96r1k7a.json key: cord-332185-a96r1k7a authors: Zhang, Shuyuan; Qiao, Shuyuan; Yu, Jinfang; Zeng, Jianwei; Shan, Sisi; Lan, Jun; Tian, Long; Zhang, Linqi; Wang, Xinquan title: Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution date: 2020-09-22 journal: bioRxiv DOI: 10.1101/2020.09.21.307439 sha: doc_id: 332185 cord_uid: a96r1k7a file: cache/cord-329395-4k8js9v2.json key: cord-329395-4k8js9v2 authors: Ratcliff, Jeremy; Nguyen, Dung; Andersson, Monique; Simmonds, Peter title: Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA date: 2020-07-01 journal: bioRxiv DOI: 10.1101/2020.06.24.168013 sha: doc_id: 329395 cord_uid: 4k8js9v2 file: cache/cord-329504-91te3nu8.json key: cord-329504-91te3nu8 authors: Croll, Tristan; Diederichs, Kay; Fischer, Florens; Fyfe, Cameron; Gao, Yunyun; Horrell, Sam; Joseph, Agnel Praveen; Kandler, Luise; Kippes, Oliver; Kirsten, Ferdinand; Müller, Konstantin; Nolte, Kristoper; Payne, Alex; Reeves, Matthew G.; Richardson, Jane; Santoni, Gianluca; Stäb, Sabrina; Tronrud, Dale; Williams, Christopher; Thorn, Andrea title: Making the invisible enemy visible date: 2020-10-07 journal: bioRxiv DOI: 10.1101/2020.10.07.307546 sha: doc_id: 329504 cord_uid: 91te3nu8 file: cache/cord-329840-f3dsu36p.json key: cord-329840-f3dsu36p authors: Hati, Sanchita; Bhattacharyya, Sudeep title: Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date: 2020-05-11 journal: bioRxiv DOI: 10.1101/2020.05.07.083147 sha: doc_id: 329840 cord_uid: f3dsu36p file: cache/cord-330743-o11d0aa1.json key: cord-330743-o11d0aa1 authors: Yu, Xi; Zhang, Liming; Tong, Liangqin; Zhang, Nana; Wang, Han; Yang, Yun; Shi, Mingyu; Xiao, Xiaoping; Zhu, Yibin; Wang, Penghua; Ding, Qiang; Zhang, Linqi; Qin, Chengfeng; Cheng, Gong title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date: 2020-05-25 journal: bioRxiv DOI: 10.1101/2020.05.22.109900 sha: doc_id: 330743 cord_uid: o11d0aa1 file: cache/cord-330337-d41imvo7.json key: cord-330337-d41imvo7 authors: Basu, Souradip; Mukhopadhyay, Suparba; Das, Rajdeep; Mukhopadhyay, Sarmishta; Singh, Pankaj Kumar; Ganguli, Sayak title: Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date: 2020-10-20 journal: bioRxiv DOI: 10.1101/2020.10.20.347021 sha: doc_id: 330337 cord_uid: d41imvo7 file: cache/cord-329129-t84pu00z.json key: cord-329129-t84pu00z authors: Zuo, J; Dowell, A; Pearce, H; Verma, K; Long, HM; Begum, J; Aiano, F; Amin-Chowdhury, Z; Hallis, B; Stapley, L; Borrow, R; Linley, E; Ahmad, S; Parker, B; Horsley, A; Amirthalingam, G; Brown, K; Ramsay, ME; Ladhani, S; Moss, P title: Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.11.01.362319 sha: doc_id: 329129 cord_uid: t84pu00z file: cache/cord-331786-wgt7kg6f.json key: cord-331786-wgt7kg6f authors: Diego-Martin, Borja; González, Beatriz; Vazquez-Vilar, Marta; Selma, Sara; Mateos-Fernández, Rubén; Gianoglio, Silvia; Fernández-del-Carmen, Asun; Orzáez, Diego title: Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities date: 2020-10-13 journal: bioRxiv DOI: 10.1101/2020.10.13.331306 sha: doc_id: 331786 cord_uid: wgt7kg6f file: cache/cord-329855-pr7g6ivu.json key: cord-329855-pr7g6ivu authors: Kalfaoglu, Bahire; Almeida-Santos, José; Adele Tye, Chanidapa; Satou, Yorifumi; Ono, Masahiro title: T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis date: 2020-05-30 journal: bioRxiv DOI: 10.1101/2020.05.26.115923 sha: doc_id: 329855 cord_uid: pr7g6ivu file: cache/cord-333703-1ku3jc9s.json key: cord-333703-1ku3jc9s authors: Kraus, Aurora; Casadei, Elisa; Huertas, Mar; Ye, Chunyan; Bradfute, Steven; Boudinot, Pierre; Levraud, Jean-Pierre; Salinas, Irene title: A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date: 2020-11-08 journal: bioRxiv DOI: 10.1101/2020.11.06.368191 sha: doc_id: 333703 cord_uid: 1ku3jc9s file: cache/cord-328659-miujzgtd.json key: cord-328659-miujzgtd authors: Mishra, Akhilesh; Pandey, Ashutosh Kumar; Gupta, Parul; Pradhan, Prashant; Dhamija, Sonam; Gomes, James; Kundu, Bishwajit; Vivekanandan, Perumal; Menon, Manoj B. title: Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions date: 2020-07-27 journal: bioRxiv DOI: 10.1101/2020.05.07.082768 sha: doc_id: 328659 cord_uid: miujzgtd file: cache/cord-334313-v2syspu6.json key: cord-334313-v2syspu6 authors: Long, S. Wesley; Olsen, Randall J.; Christensen, Paul A.; Bernard, David W.; Davis, James R.; Shukla, Maulik; Nguyen, Marcus; Ojeda Saavedra, Matthew; Cantu, Concepcion C.; Yerramilli, Prasanti; Pruitt, Layne; Subedi, Sishir; Hendrickson, Heather; Eskandari, Ghazaleh; Kumaraswami, Muthiah; McLellan, Jason S.; Musser, James M. title: Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date: 2020-05-03 journal: bioRxiv DOI: 10.1101/2020.05.01.072652 sha: doc_id: 334313 cord_uid: v2syspu6 file: cache/cord-332539-v1bfm57x.json key: cord-332539-v1bfm57x authors: Gohl, Daryl M.; Garbe, John; Grady, Patrick; Daniel, Jerry; Watson, Ray H. B.; Auch, Benjamin; Nelson, Andrew; Yohe, Sophia; Beckman, Kenneth B. title: A Rapid, Cost-Effective Tailed Amplicon Method for Sequencing SARS-CoV-2 date: 2020-05-11 journal: bioRxiv DOI: 10.1101/2020.05.11.088724 sha: doc_id: 332539 cord_uid: v1bfm57x file: cache/cord-335118-oa9jfots.json key: cord-335118-oa9jfots authors: Taka, E.; Yilmaz, S. Z.; Golcuk, M.; Kilinc, C.; Aktas, U.; Yildiz, A.; Gur, M. title: Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor date: 2020-09-21 journal: bioRxiv DOI: 10.1101/2020.09.21.305490 sha: doc_id: 335118 cord_uid: oa9jfots file: cache/cord-334624-chnibsa1.json key: cord-334624-chnibsa1 authors: Hayn, Manuel; Hirschenberger, Maximilian; Koepke, Lennart; Straub, Jan H; Nchioua, Rayhane; Christensen, Maria H; Klute, Susanne; Bozzo, Caterina Prelli; Aftab, Wasim; Zech, Fabian; Conzelmann, Carina; Müller, Janis A; Badarinarayan, Smitha Srinivasachar; Stürzel, Christina M; Forne, Ignasi; Stenger, Steffen; Conzelmann, Karl-Klaus; Münch, Jan; Sauter, Daniel; Schmidt, Florian I; Imhof, Axel; Kirchhoff, Frank; Sparrer, Konstantin MJ title: Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date: 2020-10-30 journal: bioRxiv DOI: 10.1101/2020.10.15.340612 sha: doc_id: 334624 cord_uid: chnibsa1 file: cache/cord-334220-sqvfr31q.json key: cord-334220-sqvfr31q authors: Messina, Francesco; Giombini, Emanuela; Montaldo, Chiara; Sharma, Ashish Arunkumar; Piacentini, Mauro; Zoccoli, Antonio; Sekaly, Rafick-Pierre; Locatelli, Franco; Zumla, Alimuddin; Maeurer, Markus; Capobianchi, Maria R.; Lauria, Francesco Nicola; Ippolito, Giuseppe title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 journal: bioRxiv DOI: 10.1101/2020.11.03.366666 sha: doc_id: 334220 cord_uid: sqvfr31q file: cache/cord-334300-hnrmaytm.json key: cord-334300-hnrmaytm authors: Ventura Fernandes, Bianca H; Feitosa, Natália Martins; Barbosa, Ana Paula; Bomfim, Camila Gasque; Garnique, Anali M. B.; Gomes, Francisco I. F.; Nakajima, Rafael T.; Belo, Marco A. A.; Eto, Silas Fernandes; Fernandes, Dayanne Carla; Malafaia, Guilherme; Manrique, Wilson G.; Conde, Gabriel; Rosales, Roberta R. C.; Todeschini, Iris; Rivero, Ilo; Llontop, Edgar; Sgro, German G.; Oka, Gabriel Umaji; Bueno, Natalia F; Ferraris, Fausto K.; de Magalhaes, Mariana T. Q.; Medeiros, Renata J.; Gomes, Juliana M. M; de Souza Junqueira, Mara; Conceição, Katia; Pontes, Letícia G.; Condino-Neto, Antonio; Perez, Andrea C.; Barcellos, Leonardo J. G.; Correa junior, Jose Dias; Dorlass, Erick G.; Camara, Niels O. S; Durigon, Edison Luiz; Cunha, Fernando Q.; Nóbrega, Rafael H.; Machado-Santelli, Glaucia M.; Farah, Chuck; Veras, Flávio P; Galindo-Villegas, Jorge; Costa-Lotufo, Leticia; Cunha, Thiago M.; Chammas, Roger; Guzzo, Cristiane R.; Carvalho, Luciani R; Charlie-Silva, Ives title: Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction date: 2020-10-20 journal: bioRxiv DOI: 10.1101/2020.10.20.346262 sha: doc_id: 334300 cord_uid: hnrmaytm file: cache/cord-336012-8klkojpo.json key: cord-336012-8klkojpo authors: Harilal, Divinlal; Ramaswamy, Sathishkumar; Loney, Tom; Suwaidi, Hanan Al; Khansaheb, Hamda; Alkhaja, Abdulmajeed; Varghese, Rupa; Deesi, Zulfa; Nowotny, Norbert; Alsheikh-Ali, Alawi; Tayoun, Ahmad Abou title: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission date: 2020-06-18 journal: bioRxiv DOI: 10.1101/2020.06.06.138339 sha: doc_id: 336012 cord_uid: 8klkojpo file: cache/cord-332374-cbiw6yvb.json key: cord-332374-cbiw6yvb authors: Israeli, Ofir; Beth-Din, Adi; Paran, Nir; Stein, Dana; Lazar, Shirley; Weiss, Shay; Milrot, Elad; Atiya-Nasagi, Yafit; Yitzhaki, Shmuel; Laskar, Orly; Schuster, Ofir title: Evaluating the efficacy of RT-qPCR SARS-CoV-2 direct approaches in comparison to RNA extraction date: 2020-06-10 journal: bioRxiv DOI: 10.1101/2020.06.10.144196 sha: doc_id: 332374 cord_uid: cbiw6yvb file: cache/cord-336343-qbcb9qi3.json key: cord-336343-qbcb9qi3 authors: Agarwal, Ajay title: in-silica Analysis of SARS-CoV-2 viral strain using Reverse Vaccinology Approach: A Case Study for USA date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.16.154559 sha: doc_id: 336343 cord_uid: qbcb9qi3 file: cache/cord-331888-lbtuvdv3.json key: cord-331888-lbtuvdv3 authors: de Souza, Dalton Garcia Borges; Alves Júnior, Francisco Tarcísio; Soma, Nei Yoshihiro title: Forecasting COVID-19 cases at the Amazon region: a comparison of classical and machine learning models date: 2020-10-09 journal: bioRxiv DOI: 10.1101/2020.10.09.332908 sha: doc_id: 331888 cord_uid: lbtuvdv3 file: cache/cord-333089-ufyzqgqk.json key: cord-333089-ufyzqgqk authors: Aguilar-Pineda, Jorge Alberto; Albaghdadi, Mazen; Jiang, Wanlin; Lopez, Karin J. Vera; Del-Carpio, Gonzalo Davila; Valdez, Badhin Gómez; Lindsay, Mark E.; Malhotra, Rajeev; Lino Cardenas, Christian L. title: Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date: 2020-07-29 journal: bioRxiv DOI: 10.1101/2020.07.29.227249 sha: doc_id: 333089 cord_uid: ufyzqgqk file: cache/cord-335652-v98gv5uf.json key: cord-335652-v98gv5uf authors: Salazar, Cecilia; Díaz-Viraqué, Florencia; Pereira-Gómez, Marianoel; Ferrés, Ignacio; Moreno, Pilar; Moratorio, Gonzalo; Iraola, Gregorio title: Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date: 2020-05-10 journal: bioRxiv DOI: 10.1101/2020.05.09.086223 sha: doc_id: 335652 cord_uid: v98gv5uf file: cache/cord-334394-qgyzk7th.json key: cord-334394-qgyzk7th authors: Edgar, Robert C.; Taylor, Jeff; Altman, Tomer; Barbera, Pierre; Meleshko, Dmitry; Lin, Victor; Lohr, Dan; Novakovsky, Gherman; Al-Shayeb, Basem; Banfield, Jillian F.; Korobeynikov, Anton; Chikhi, Rayan; Babaian, Artem title: Petabase-scale sequence alignment catalyses viral discovery date: 2020-08-10 journal: bioRxiv DOI: 10.1101/2020.08.07.241729 sha: doc_id: 334394 cord_uid: qgyzk7th file: cache/cord-334891-4jgtxg07.json key: cord-334891-4jgtxg07 authors: Choudhury, Abhigyan; Chandra Das, Nabarun; Patra, Ritwik; Bhattacharya, Manojit; Mukherjee, Suprabhat title: In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human date: 2020-11-11 journal: bioRxiv DOI: 10.1101/2020.11.11.377713 sha: doc_id: 334891 cord_uid: 4jgtxg07 file: cache/cord-331680-qlzhtxs0.json key: cord-331680-qlzhtxs0 authors: Goryachev, A.N.; Kalantarov, S.A.; Severova, A.G.; Goryacheva, A.S. title: Potential Opportunity of Antisense Therapy of COVID-19 on an in Vitro Model date: 2020-11-03 journal: bioRxiv DOI: 10.1101/2020.11.02.363598 sha: doc_id: 331680 cord_uid: qlzhtxs0 file: cache/cord-336628-0evl3wnd.json key: cord-336628-0evl3wnd authors: Neufeldt, Christopher J.; Cerikan, Berati; Cortese, Mirko; Frankish, Jamie; Lee, Ji-Young; Plociennikowska, Agnieszka; Heigwer, Florian; Joecks, Sebastian; Burkart, Sandy S.; Zander, David Y.; Gendarme, Mathieu; El Debs, Bachir; Halama, Niels; Merle, Uta; Boutros, Michael; Binder, Marco; Bartenschlager, Ralf title: SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB date: 2020-07-21 journal: bioRxiv DOI: 10.1101/2020.07.21.212639 sha: doc_id: 336628 cord_uid: 0evl3wnd file: cache/cord-332271-slouuryl.json key: cord-332271-slouuryl authors: Baker, Jeremy D.; Uhrich, Rikki L.; Kraemer, Gerald C.; Love, Jason E.; Kraemer, Brian C. title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease date: 2020-08-27 journal: bioRxiv DOI: 10.1101/2020.07.10.197889 sha: doc_id: 332271 cord_uid: slouuryl file: cache/cord-334584-xh41koro.json key: cord-334584-xh41koro authors: Dilucca, Maddalena; Forcelloni, Sergio; Georgakilas, Alexandros G.; Giansanti, Andrea; Pavlopoulou, Athanasia title: Temporal evolution and adaptation of SARS-COV 2 codon usage date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.29.123976 sha: doc_id: 334584 cord_uid: xh41koro file: cache/cord-335443-iv2gs3kg.json key: cord-335443-iv2gs3kg authors: Kim, Youngchang; Wower, Jacek; Maltseva, Natalia; Chang, Changsoo; Jedrzejczak, Robert; Wilamowski, Mateusz; Kang, Soowon; Nicolaescu, Vlad; Randall, Glenn; Michalska, Karolina; Joachimiak, Andrzej title: Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 date: 2020-06-28 journal: bioRxiv DOI: 10.1101/2020.06.26.173872 sha: doc_id: 335443 cord_uid: iv2gs3kg file: cache/cord-336793-9bbyu1qx.json key: cord-336793-9bbyu1qx authors: Matsuyama, Shutoku; Kawase, Miyuki; Nao, Naganori; Shirato, Kazuya; Ujike, Makoto; Kamitani, Wataru; Shimojima, Masayuki; Fukushi, Shuetsu title: The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells date: 2020-08-24 journal: bioRxiv DOI: 10.1101/2020.08.22.258459 sha: doc_id: 336793 cord_uid: 9bbyu1qx file: cache/cord-336560-m5u6ryy9.json key: cord-336560-m5u6ryy9 authors: Boudewijns, Robbert; Thibaut, Hendrik Jan; Kaptein, Suzanne J. F.; Li, Rong; Vergote, Valentijn; Seldeslachts, Laura; De Keyzer, Carolien; Bervoets, Lindsey; Sharma, Sapna; Van Weyenbergh, Johan; Liesenborghs, Laurens; Ma, Ji; Jansen, Sander; Van Looveren, Dominique; Vercruysse, Thomas; Jochmans, Dirk; Wang, Xinyu; Martens, Erik; Roose, Kenny; De Vlieger, Dorien; Schepens, Bert; Van Buyten, Tina; Jacobs, Sofie; Liu, Yanan; Martí-Carreras, Joan; Vanmechelen, Bert; Wawina-Bokalanga, Tony; Delang, Leen; Rocha-Pereira, Joana; Coelmont, Lotte; Chiu, Winston; Leyssen, Pieter; Heylen, Elisabeth; Schols, Dominique; Wang, Lanjiao; Close, Lila; Matthijnssens, Jelle; Van Ranst, Marc; Compernolle, Veerle; Schramm, Georg; Van Laere, Koen; Saelens, Xavier; Callewaert, Nico; Opdenakker, Ghislain; Maes, Piet; Weynand, Birgit; Cawthorne, Christopher; Velde, Greetje Vande; Wang, Zhongde; Neyts, Johan; Dallmeier, Kai title: STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters date: 2020-07-02 journal: bioRxiv DOI: 10.1101/2020.04.23.056838 sha: doc_id: 336560 cord_uid: m5u6ryy9 file: cache/cord-338296-2hk7h132.json key: cord-338296-2hk7h132 authors: Malla, Tek Narsingh; Pandey, Suraj; Poudyal, Ishwor; Feliz, Denisse; Noda, Moraima; Phillips, George; Stojkovic, Emina; Schmidt, Marius title: Ebselen Reacts with SARS Coronavirus-2 Main Protease Crystals date: 2020-08-23 journal: bioRxiv DOI: 10.1101/2020.08.10.244525 sha: doc_id: 338296 cord_uid: 2hk7h132 file: cache/cord-335075-6wo2o5pp.json key: cord-335075-6wo2o5pp authors: Bangaru, Sandhya; Ozorowski, Gabriel; Turner, Hannah L.; Antanasijevic, Aleksandar; Huang, Deli; Wang, Xiaoning; Torres, Jonathan L.; Diedrich, Jolene K.; Tian, Jing-Hui; Portnoff, Alyse D.; Patel, Nita; Massare, Michael J.; Yates, John R.; Nemazee, David; Paulson, James C.; Glenn, Greg; Smith, Gale; Ward, Andrew B. title: Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate date: 2020-08-06 journal: bioRxiv DOI: 10.1101/2020.08.06.234674 sha: doc_id: 335075 cord_uid: 6wo2o5pp file: cache/cord-339012-4juhmjaj.json key: cord-339012-4juhmjaj authors: Hou, Wei; Liu, Fei; van der Poel, Wim H.M.; Hulst, Marcel M. title: Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date: 2020-07-28 journal: bioRxiv DOI: 10.1101/2020.07.28.224576 sha: doc_id: 339012 cord_uid: 4juhmjaj file: cache/cord-339720-d1stzy8w.json key: cord-339720-d1stzy8w authors: Zhao, Yuan; Wang, Junbin; Kuang, Dexuan; Xu, Jingwen; Yang, Mengli; Ma, Chunxia; Zhao, Siwen; Li, Jingmei; Long, Haiting; Ding, Kaiyun; Gao, Jiahong; Liu, Jiansheng; Wang, Haixuan; Li, Haiyan; Yang, Yun; Yu, Wenhai; Yang, Jing; Zheng, Yinqiu; Wu, Daoju; Lu, Shuaiyao; Liu, Hongqi; Peng, Xiaozhong title: Susceptibility of tree shrew to SARS-CoV-2 infection date: 2020-04-30 journal: bioRxiv DOI: 10.1101/2020.04.30.029736 sha: doc_id: 339720 cord_uid: d1stzy8w file: cache/cord-336938-03366q9t.json key: cord-336938-03366q9t authors: Thacker, Vivek V; Sharma, Kunal; Dhar, Neeraj; Mancini, Gian-Filippo; Sordet-Dessimoz, Jessica; Mckinney, John D title: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model date: 2020-08-10 journal: bioRxiv DOI: 10.1101/2020.08.10.243220 sha: doc_id: 336938 cord_uid: 03366q9t file: cache/cord-339772-q814d6l7.json key: cord-339772-q814d6l7 authors: Pach, Szymon; Nguyen, Trung Ngoc; Trimpert, Jakob; Kunec, Dusan; Osterrieder, Nikolaus; Wolber, Gerhard title: ACE2-Variants Indicate Potential SARS-CoV-2-Susceptibility in Animals: An Extensive Molecular Dynamics Study date: 2020-05-14 journal: bioRxiv DOI: 10.1101/2020.05.14.092767 sha: doc_id: 339772 cord_uid: q814d6l7 file: cache/cord-338055-2d6n4cve.json key: cord-338055-2d6n4cve authors: Hassan, Sk. Sarif; Ghosh, Shinjini; Attrish, Diksha; Choudhury, Pabitra Pal; Seyran, Murat; Pizzol, Damiano; Adadi, Parise; El-Aziz, Tarek Mohamed Abd; Soares, Antonio; Kandimalla, Ramesh; Lundstrom, Kenneth; Tambuwala, Murtaza; Aljabali, Alaa A. A.; Lal, Amos; Azad, Gajendra Kumar; Uversky, Vladimir N.; Sherchan, Samendra P.; Baetas-da-Cruz, Wagner; Uhal, Bruce D.; Rezaei, Nima; Brufsky, Adam M. title: A unique view of SARS-CoV-2 through the lens of ORF8 protein date: 2020-08-26 journal: bioRxiv DOI: 10.1101/2020.08.25.267328 sha: doc_id: 338055 cord_uid: 2d6n4cve file: cache/cord-338734-laeocs3j.json key: cord-338734-laeocs3j authors: Lima, Amorce; Healer, Vicki; Vendrone, Elaine; Silbert, Suzane title: Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen date: 2020-06-30 journal: bioRxiv DOI: 10.1101/2020.06.29.179192 sha: doc_id: 338734 cord_uid: laeocs3j file: cache/cord-339431-kyr5lv15.json key: cord-339431-kyr5lv15 authors: Saçar Demirci, Müşerref Duygu; Adan, Aysun title: Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection date: 2020-03-17 journal: bioRxiv DOI: 10.1101/2020.03.15.992438 sha: doc_id: 339431 cord_uid: kyr5lv15 file: cache/cord-336522-y9nzsv95.json key: cord-336522-y9nzsv95 authors: Rosenke, Kyle; Leventhal, Shanna; Moulton, Hong M.; Hatlevig, Susan; Hawman, David; Feldmann, Heinz; Stein, David A. title: Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino-oligomers date: 2020-09-30 journal: bioRxiv DOI: 10.1101/2020.09.29.319731 sha: doc_id: 336522 cord_uid: y9nzsv95 file: cache/cord-341768-k86gsfng.json key: cord-341768-k86gsfng authors: Suresh, Voddu; Parida, Deepti; Minz, Aliva P.; Senapati, Shantibhusan title: Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies date: 2020-06-29 journal: bioRxiv DOI: 10.1101/2020.06.29.177154 sha: doc_id: 341768 cord_uid: k86gsfng file: cache/cord-341502-jlzufa28.json key: cord-341502-jlzufa28 authors: Lee, Sungyul; Lee, Young-suk; Choi, Yeon; Son, Ahyeon; Park, Youngran; Lee, Kyung-Min; Kim, Jeesoo; Kim, Jong-Seo; Kim, V. Narry title: The SARS-CoV-2 RNA interactome date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.11.02.364497 sha: doc_id: 341502 cord_uid: jlzufa28 file: cache/cord-340240-dk48pdqa.json key: cord-340240-dk48pdqa authors: Kuo, Tsun-Yung; Lin, Meei-Yun; Coffman, Robert L; Campbell, John D; Traquina, Paula; Lin, Yi-Jiun; Liu, Luke Tzu-Chi; Cheng, Jinyi; Wu, Yu-Chi; Wu, Chung-Chin; Tang, Wei-Hsuan; Huang, Chung-Guei; Tsao, Kuo-Chien; Shih, Shin-Ru; Chen, Charles title: Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 date: 2020-08-11 journal: bioRxiv DOI: 10.1101/2020.08.11.245704 sha: doc_id: 340240 cord_uid: dk48pdqa file: cache/cord-342010-5mkf67os.json key: cord-342010-5mkf67os authors: Levasseur, Anthony; Delerce, Jeremy; Caputo, Aurelia; Brechard, Ludivine; Colson, Philippe; Lagier, Jean-Christophe; Fournier, Pierre-Edouard; Raoult, Didier title: Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients date: 2020-09-04 journal: bioRxiv DOI: 10.1101/2020.09.04.282616 sha: doc_id: 342010 cord_uid: 5mkf67os file: cache/cord-337973-djqzgc1k.json key: cord-337973-djqzgc1k authors: Hao, Siyuan; Ning, Kang; Kuz, Cagla Aksu; Vorhies, Kai; Yan, Ziying; Qiu, Jianming title: Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium date: 2020-08-28 journal: bioRxiv DOI: 10.1101/2020.08.27.271130 sha: doc_id: 337973 cord_uid: djqzgc1k file: cache/cord-337701-56tmg38b.json key: cord-337701-56tmg38b authors: Xiao, Yan; Li, Zhen; Wang, Xinming; Wang, Yingying; Wang, Ying; Wang, Geng; Ren, Lili; Li, Jianguo title: Comparison of three TaqMan Real-Time Reverse Transcription-PCR assays in detecting SARS-CoV-2 date: 2020-07-06 journal: bioRxiv DOI: 10.1101/2020.07.06.189860 sha: doc_id: 337701 cord_uid: 56tmg38b file: cache/cord-338543-q6cl5kjp.json key: cord-338543-q6cl5kjp authors: Salguero, Francisco J.; White, Andrew D.; Slack, Gillian S.; Fotheringham, Susan A.; Bewley, Kevin R.; Gooch, Karen E.; Longet, Stephanie; Humphries, Holly E.; Watson, Robert J.; Hunter, Laura; Ryan, Kathryn A.; Hall, Yper; Sibley, Laura; Sarfas, Charlotte; Allen, Lauren; Aram, Marilyn; Brunt, Emily; Brown, Phillip; Buttigieg, Karen R.; Cavell, Breeze E.; Cobb, Rebecca; Coombes, Naomi S.; Daykin-Pont, Owen; Elmore, Michael J.; Gkolfinos, Konstantinos; Godwin, Kerry J.; Gouriet, Jade; Halkerston, Rachel; Harris, Debbie J.; Hender, Thomas; Ho, Catherine M.K.; Kennard, Chelsea L.; Knott, Daniel; Leung, Stephanie; Lucas, Vanessa; Mabbutt, Adam; Morrison, Alexandra L.; Ngabo, Didier; Paterson, Jemma; Penn, Elizabeth J.; Pullan, Steve; Taylor, Irene; Tipton, Tom; Thomas, Stephen; Tree, Julia A.; Turner, Carrie; Wand, Nadina; Wiblin, Nathan R.; Charlton, Sue; Hallis, Bassam; Pearson, Geoffrey; Rayner, Emma L.; Nicholson, Andrew G.; Funnell, Simon G.; Dennis, Mike J.; Gleeson, Fergus V.; Sharpe, Sally; Carroll, Miles W. title: Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19 date: 2020-09-17 journal: bioRxiv DOI: 10.1101/2020.09.17.301093 sha: doc_id: 338543 cord_uid: q6cl5kjp file: cache/cord-339665-nwwutduy.json key: cord-339665-nwwutduy authors: Patel, Ami; Walters, Jewell; Reuschel, Emma L.; Schultheis, Katherine; Parzych, Elizabeth; Gary, Ebony N.; Maricic, Igor; Purwar, Mansi; Eblimit, Zeena; Walker, Susanne N.; Guimet, Diana; Bhojnagarwala, Pratik; Doan, Arthur; Xu, Ziyang; Elwood, Dustin; Reeder, Sophia M.; Pessaint, Laurent; Kim, Kevin Y.; Cook, Anthony; Chokkalingam, Neethu; Finneyfrock, Brad; Tello-Ruiz, Edgar; Dodson, Alan; Choi, Jihae; Generotti, Alison; Harrison, John; Tursi, Nicholas J.; Andrade, Viviane M.; Dia, Yaya; Zaidi, Faraz I.; Andersen, Hanne; Lewis, Mark G.; Muthumani, Kar; Kim, J Joseph; Kulp, Daniel W.; Humeau, Laurent M.; Ramos, Stephanie; Smith, Trevor R.F.; Weiner, David B.; Broderick, Kate E. title: Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date: 2020-07-29 journal: bioRxiv DOI: 10.1101/2020.07.28.225649 sha: doc_id: 339665 cord_uid: nwwutduy file: cache/cord-342942-1s32o9m8.json key: cord-342942-1s32o9m8 authors: Stamatakis, George; Samiotaki, Martina; Mpakali, Anastasia; Panayotou, George; Stratikos, Efstratios title: Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases date: 2020-06-22 journal: bioRxiv DOI: 10.1101/2020.06.22.164681 sha: doc_id: 342942 cord_uid: 1s32o9m8 file: cache/cord-342657-od48cntc.json key: cord-342657-od48cntc authors: Klemm, Theresa; Ebert, Gregor; Calleja, Dale J.; Allison, Cody C.; Richardson, Lachlan W.; Bernardini, Jonathan P.; Lu, Bernadine G. C.; Kuchel, Nathan W.; Grohmann, Christoph; Shibata, Yuri; Gan, Zhong Yan; Cooney, James P.; Doerflinger, Marcel; Au, Amanda E.; Blackmore, Timothy R.; Geurink, Paul P.; Ovaa, Huib; Newman, Janet; Riboldi-Tunnicliffe, Alan; Czabotar, Peter E.; Mitchell, Jeffrey P.; Feltham, Rebecca; Lechtenberg, Bernhard C.; Lowes, Kym N.; Dewson, Grant; Pellegrini, Marc; Lessene, Guillaume; Komander, David title: Mechanism and inhibition of SARS-CoV-2 PLpro date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.18.160614 sha: doc_id: 342657 cord_uid: od48cntc file: cache/cord-340432-vm6m0kb4.json key: cord-340432-vm6m0kb4 authors: Srivastava, Sukrit; Verma, Sonia; Kamthania, Mohit; Agarwal, Deepa; Saxena, Ajay Kumar; Kolbe, Michael; Singh, Sarman; Kotnis, Ashwin; Rathi, Brijesh; Nayar, Seema. A.; Shin, Ho-Joon; Vashisht, Kapil; Pandey, Kailash C title: Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.06.284992 sha: doc_id: 340432 cord_uid: vm6m0kb4 file: cache/cord-342599-558yn6pu.json key: cord-342599-558yn6pu authors: Rinchai, Darawan; Kabeer, Basirudeen; Toufiq, Mohammed; Calderone, Zohreh; Deola, Sara; Brummaier, Tobias; Garand, Mathieu; Branco, Ricardo; Baldwin, Nicole; Alfaki, Mohamed; Altman, Matthew; Ballestrero, Alberto; Bassetti, Matteo; Zoppoli, Gabriele; De Maria, Andrea; Tang, Benjamin; Bedognetti, Davide; Chaussabel, Damien title: A modular framework for the development of targeted Covid-19 blood transcript profiling panels date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.20.107243 sha: doc_id: 342599 cord_uid: 558yn6pu file: cache/cord-343586-28ezisog.json key: cord-343586-28ezisog authors: Rocca, María Florencia; Zintgraff, Jonathan Cristian; Dattero, María Elena; Santos, Leonardo Silva; Ledesma, Martín; Vay, Carlos; Prieto, Mónica; Benedetti, Estefanía; Avaro, Martín; Russo, Mara; Nachtigall, Fabiane Manke; Baumeister, Elsa title: A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs date: 2020-05-07 journal: bioRxiv DOI: 10.1101/2020.05.07.082925 sha: doc_id: 343586 cord_uid: 28ezisog file: cache/cord-344909-0o55l4iy.json key: cord-344909-0o55l4iy authors: Cross, Robert W.; Prasad, Abhishek N.; Borisevich, Viktoriya; Woolsey, Courtney; Agans, Krystle N.; Deer, Daniel J.; Dobias, Natalie S.; Geisbert, Joan B.; Fenton, Karla A.; Geisbert, Thomas W. title: Use of convalescent serum reduces severity of COVID-19 in nonhuman primates date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.14.340091 sha: doc_id: 344909 cord_uid: 0o55l4iy file: cache/cord-342456-5gp3cry0.json key: cord-342456-5gp3cry0 authors: Hoagland, Daisy A.; Clarke, Daniel J.B.; Møller, Rasmus; Han, Yuling; Yang, Liuliu; Wojciechowicz, Megan L.; Lachmann, Alexander; Oguntuyo, Kasopefoluwa Y.; Stevens, Christian; Lee, Benhur; Chen, Shuibing; Ma’ayan, Avi; tenOever, Benjamin R title: Modulating the transcriptional landscape of SARS-CoV-2 as an effective method for developing antiviral compounds date: 2020-07-13 journal: bioRxiv DOI: 10.1101/2020.07.12.199687 sha: doc_id: 342456 cord_uid: 5gp3cry0 file: cache/cord-340516-9dfaqsv7.json key: cord-340516-9dfaqsv7 authors: Moore, Anne C.; Dora, Emery G.; Peinovich, Nadine; Tucker, Kiersten P.; Lin, Karen; Cortese, Mario; Tucker, Sean N. title: Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.04.283853 sha: doc_id: 340516 cord_uid: 9dfaqsv7 file: cache/cord-342015-bz2vab6e.json key: cord-342015-bz2vab6e authors: Ouadfeul, Sid-Ali title: Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date: 2020-08-16 journal: bioRxiv DOI: 10.1101/2020.08.15.252411 sha: doc_id: 342015 cord_uid: bz2vab6e file: cache/cord-340291-bah2ege0.json key: cord-340291-bah2ege0 authors: Kohmer, Niko; Westhaus, Sandra; Rühl, Cornelia; Ciesek, Sandra; Rabenau, Holger F. title: Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity date: 2020-05-10 journal: bioRxiv DOI: 10.1101/2020.05.08.085506 sha: doc_id: 340291 cord_uid: bah2ege0 file: cache/cord-343027-ks3fn9pq.json key: cord-343027-ks3fn9pq authors: Fraser, Nicholas; Brierley, Liam; Dey, Gautam; Polka, Jessica K; Pálfy, Máté; Nanni, Federico; Coates, Jonathon Alexis title: Preprinting the COVID-19 pandemic date: 2020-09-18 journal: bioRxiv DOI: 10.1101/2020.05.22.111294 sha: doc_id: 343027 cord_uid: ks3fn9pq file: cache/cord-346299-2s9j01q7.json key: cord-346299-2s9j01q7 authors: Salim Khan, S Muhammad; Qurieshi, Mariya Amin; Haq, Inaamul; Majid, Sabhiya; Bhat, Arif Akbar; Nabi, Sahila; Ganai, Nisar Ahmad; Zahoor, Nazia; Nisar, Auqfeen; Chowdri, Iqra Nisar; Qazi, Tanzeela Bashir; Kousar, Rafiya; Lone, Abdul Aziz; Sabah, Iram; Nabi, Shahroz; Sumji, Ishtiyaq Ahmad; Kawoosa, Misbah Ferooz; Ayoub, Shifana title: Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study date: 2020-09-04 journal: bioRxiv DOI: 10.1101/2020.09.04.282640 sha: doc_id: 346299 cord_uid: 2s9j01q7 file: cache/cord-343317-97n1j0jj.json key: cord-343317-97n1j0jj authors: Duan, Xiaohua; Han, Yuling; Yang, Liuliu; Nilsson-Payant, Benjamin E.; Wang, Pengfei; Zhang, Tuo; Xiang, Jenny; Xu, Dong; Wang, Xing; Uhl, Skyler; Huang, Yaoxing; Chen, Huanhuan Joyce; Wang, Hui; tenOever, Benjamin; Schwartz, Robert E.; Ho, David. D.; Evans, Todd; Pan, Fong Cheng; Chen, Shuibing title: Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date: 2020-05-02 journal: bioRxiv DOI: 10.1101/2020.05.02.073320 sha: doc_id: 343317 cord_uid: 97n1j0jj file: cache/cord-333420-qqyg9um9.json key: cord-333420-qqyg9um9 authors: Zhu, Xun; Chang, Ti-Cheng; Webby, Richard; Wu, Gang title: idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates date: 2020-10-09 journal: bioRxiv DOI: 10.1101/2020.10.08.330456 sha: doc_id: 333420 cord_uid: qqyg9um9 file: cache/cord-344236-qp3ianzf.json key: cord-344236-qp3ianzf authors: Ali, Fedaa; Elserafy, Menattallah; Alkordi, Mohamed H.; Amin, Muhamed title: ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity date: 2020-05-08 journal: bioRxiv DOI: 10.1101/2020.05.08.084384 sha: doc_id: 344236 cord_uid: qp3ianzf file: cache/cord-345405-ngpsgn63.json key: cord-345405-ngpsgn63 authors: Tremiliosi, Guilherme C.; Simoes, Luiz Gustavo P.; Minozzi, Daniel T.; Santos, Renato I.; Vilela, Daiane C. B.; Durigon, Edison Luiz; Machado, Rafael Rahal Guaragna; Medina, Douglas Sales; Ribeiro, Lara Kelly; Rosa, Ieda Lucia Viana; Assis, Marcelo; Andrés, Juan; Longo, Elson; Freitas-Junior, Lucio H. title: Ag nanoparticles-based antimicrobial polycotton fabrics to prevent the transmission and spread of SARS-CoV-2 date: 2020-06-26 journal: bioRxiv DOI: 10.1101/2020.06.26.152520 sha: doc_id: 345405 cord_uid: ngpsgn63 file: cache/cord-345299-4k7qymqd.json key: cord-345299-4k7qymqd authors: Xiong, Hua-Long; Cao, Jia-Li; Shen, Chen-Guang; Ma, Jian; Qiao, Xiao-Yang; Shi, Tian-Shu; Yang, Yang; Ge, Sheng-Xiang; Zhang, Jun; Zhang, Tian-Ying; Yuan, Quan; Xia, Ning-Shao title: Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro date: 2020-06-05 journal: bioRxiv DOI: 10.1101/2020.06.05.135996 sha: doc_id: 345299 cord_uid: 4k7qymqd file: cache/cord-345499-hq5um68k.json key: cord-345499-hq5um68k authors: Xiong, Rui; Zhang, Leike; Li, Shiliang; Sun, Yuan; Ding, Minyi; Wang, Yong; Zhao, Yongliang; Wu, Yan; Shang, Weijuan; Jiang, Xiaming; Shan, Jiwei; Shen, Zihao; Tong, Yi; Xu, Liuxin; Yu, Chen; Liu, Yingle; Zou, Gang; Lavillete, Dimitri; Zhao, Zhenjiang; Wang, Rui; Zhu, Lili; Xiao, Gengfu; Lan, Ke; Li, Honglin; Xu, Ke title: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 date: 2020-03-12 journal: bioRxiv DOI: 10.1101/2020.03.11.983056 sha: doc_id: 345499 cord_uid: hq5um68k file: cache/cord-343476-0chuwvg6.json key: cord-343476-0chuwvg6 authors: MacLean, Oscar A.; Lytras, Spyros; Singer, Joshua B.; Weaver, Steven; Pond, Sergei L. Kosakovsky; Robertson, David L. title: Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans date: 2020-05-29 journal: bioRxiv DOI: 10.1101/2020.05.28.122366 sha: doc_id: 343476 cord_uid: 0chuwvg6 file: cache/cord-347441-8ow952d8.json key: cord-347441-8ow952d8 authors: Parvez, Md Sorwer Alam; Rahman, Mohammad Mahfujur; Morshed, Md Niaz; Rahman, Dolilur; Anwar, Saeed; Hosen, Mohammad Jakir title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism date: 2020-06-07 journal: bioRxiv DOI: 10.1101/2020.06.07.138800 sha: doc_id: 347441 cord_uid: 8ow952d8 file: cache/cord-344560-662pfa61.json key: cord-344560-662pfa61 authors: Yamamoto, Norio; Matsuyama, Shutoku; Hoshino, Tyuji; Yamamoto, Naoki title: Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro date: 2020-04-08 journal: bioRxiv DOI: 10.1101/2020.04.06.026476 sha: doc_id: 344560 cord_uid: 662pfa61 file: cache/cord-343517-vf32wxkx.json key: cord-343517-vf32wxkx authors: Lokman, Syed Mohammad; Rasheduzzaman, Md.; Salauddin, Asma; Barua, Rocktim; Tanzina, Afsana Yeasmin; Rumi, Meheadi Hasan; Hossain, Md. Imran; Siddiki, Amam Zonaed; Mannan, Adnan; Hasan, Md. Mahbub title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.07.030924 sha: doc_id: 343517 cord_uid: vf32wxkx file: cache/cord-346335-el45v0a5.json key: cord-346335-el45v0a5 authors: Tan, H.S. title: Fourier spectral density of the coronavirus genome date: 2020-08-11 journal: bioRxiv DOI: 10.1101/2020.06.30.180034 sha: doc_id: 346335 cord_uid: el45v0a5 file: cache/cord-344949-9zyz4hll.json key: cord-344949-9zyz4hll authors: Luban, Jeremy; Sattler, Rachel; Mühlberger, Elke; Graci, Jason D.; Cao, Liangxian; Weetall, Marla; Trotta, Christopher; Colacino, Joseph M.; Bavari, Sina; Strambio-De-Castillia, Caterina; Suder, Ellen L.; Wang, Yetao; Soloveva, Veronica; Cintron-Lue, Katherine; Naryshkin, Nikolai A.; Pykett, Mark; Welch, Ellen M.; O’Keefe, Kylie; Kong, Ronald; Goodwin, Elizabeth; Jacobson, Allan; Paessler, Slobodan; Peltz, Stuart title: The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines date: 2020-08-05 journal: bioRxiv DOI: 10.1101/2020.08.05.238394 sha: doc_id: 344949 cord_uid: 9zyz4hll file: cache/cord-346670-34wfy52f.json key: cord-346670-34wfy52f authors: Gobeil, Sophie M-C.; Janowska, Katarzyna; McDowell, Shana; Mansouri, Katayoun; Parks, Robert; Manne, Kartik; Stalls, Victoria; Kopp, Megan; Henderson, Rory; Edwards, Robert J; Haynes, Barton F.; Acharya, Priyamvada title: D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction date: 2020-10-12 journal: bioRxiv DOI: 10.1101/2020.10.11.335299 sha: doc_id: 346670 cord_uid: 34wfy52f file: cache/cord-347714-vxxhglx7.json key: cord-347714-vxxhglx7 authors: Abitogun, Folagbade; Srivastava, R.; Sharma, S.; Komarysta, V.; Akurut, E.; Munir, N.; Macalalad, L.; Olawale, O.; Owolabi, O.; Abayomi, G.; Debnath, S. title: COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date: 2020-10-14 journal: bioRxiv DOI: 10.1101/2020.10.14.339689 sha: doc_id: 347714 cord_uid: vxxhglx7 file: cache/cord-347804-kxhasabe.json key: cord-347804-kxhasabe authors: Luo, Ruibang; Wong, Yat-Sing; Lam, Tak-Wah title: Tracking cytosine depletion in SARS-CoV-2 date: 2020-10-26 journal: bioRxiv DOI: 10.1101/2020.10.26.354787 sha: doc_id: 347804 cord_uid: kxhasabe file: cache/cord-347982-omxcdiwt.json key: cord-347982-omxcdiwt authors: Basso, Fernanda Gisele; de Paulo, Alex Fabianne; Porto, Geciane Silveira; Pereira, Cristiano Gonçalves title: Cooperative efforts on developing vaccines and therapies for COVID-19 Cooperative efforts for COVID-19 date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.09.06.282145 sha: doc_id: 347982 cord_uid: omxcdiwt file: cache/cord-346532-4xpnd93d.json key: cord-346532-4xpnd93d authors: Strömich, Léonie; Wu, Nan; Barahona, Mauricio; Yaliraki, Sophia N. title: Allosteric Hotspots in the Main Protease of SARS-CoV-2 date: 2020-11-06 journal: bioRxiv DOI: 10.1101/2020.11.06.369439 sha: doc_id: 346532 cord_uid: 4xpnd93d file: cache/cord-347472-n6811ens.json key: cord-347472-n6811ens authors: Rosebrock, Adam P. title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date: 2020-05-15 journal: bioRxiv DOI: 10.1101/2020.05.13.094839 sha: doc_id: 347472 cord_uid: n6811ens file: cache/cord-348727-o38uplxe.json key: cord-348727-o38uplxe authors: Beaudoin-Bussières, Guillaume; Laumaea, Annemarie; Anand, Sai Priya; Prévost, Jérémie; Gasser, Romain; Goyette, Guillaume; Medjahed, Halima; Perreault, Josée; Tremblay, Tony; Lewin, Antoine; Gokool, Laurie; Morrisseau, Chantal; Bégin, Philippe; Tremblay, Cécile; Martel-Laferrière, Valérie; Kaufmann, Daniel E.; Richard, Jonathan; Bazin, Renée; Finzi, Andrés title: Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals date: 2020-07-09 journal: bioRxiv DOI: 10.1101/2020.07.09.194639 sha: doc_id: 348727 cord_uid: o38uplxe file: cache/cord-346546-yffwd0dc.json key: cord-346546-yffwd0dc authors: Douangamath, Alice; Fearon, Daren; Gehrtz, Paul; Krojer, Tobias; Lukacik, Petra; Owen, C. David; Resnick, Efrat; Strain-Damerell, Claire; Aimon, Anthony; Ábrányi-Balogh, Péter; Brandaõ-Neto, José; Carbery, Anna; Davison, Gemma; Dias, Alexandre; Downes, Thomas D; Dunnett, Louise; Fairhead, Michael; Firth, James D.; Jones, S. Paul; Keely, Aaron; Keserü, György M.; Klein, Hanna F; Martin, Mathew P.; Noble, Martin E. M.; O’Brien, Peter; Powell, Ailsa; Reddi, Rambabu; Skyner, Rachael; Snee, Matthew; Waring, Michael J.; Wild, Conor; London, Nir; von Delft, Frank; Walsh, Martin A. title: Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease date: 2020-05-27 journal: bioRxiv DOI: 10.1101/2020.05.27.118117 sha: doc_id: 346546 cord_uid: yffwd0dc file: cache/cord-348635-1pb2ag9j.json key: cord-348635-1pb2ag9j authors: Anand, Praveen; Puranik, Arjun; Aravamudan, Murali; Venkatakrishnan, AJ; Soundararajan, Venky title: SARS-CoV-2 selectively mimics a cleavable peptide of human ENaC in a strategic hijack of host proteolytic machinery date: 2020-04-30 journal: bioRxiv DOI: 10.1101/2020.04.29.069476 sha: doc_id: 348635 cord_uid: 1pb2ag9j file: cache/cord-348729-kejlm425.json key: cord-348729-kejlm425 authors: Liu, Xiaoyu; Gao, Fang; Gou, Liming; Chen, Yin; Gu, Yayun; Ao, Lei; Shen, Hongbing; Hu, Zhibin; Guo, Xiling; Gao, Wei title: Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection date: 2020-05-04 journal: bioRxiv DOI: 10.1101/2020.05.03.074914 sha: doc_id: 348729 cord_uid: kejlm425 file: cache/cord-349794-mhviub6e.json key: cord-349794-mhviub6e authors: Le, Brian L.; Andreoletti, Gaia; Oskotsky, Tomiko; Vallejo-Gracia, Albert; Rosales, Romel; Yu, Katharine; Kosti, Idit; Leon, Kristoffer E.; Bunis, Daniel G.; Li, Christine; Kumar, G. Renuka; White, Kris M.; García-Sastre, Adolfo; Ott, Melanie; Sirota, Marina title: Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 date: 2020-10-23 journal: bioRxiv DOI: 10.1101/2020.10.23.352666 sha: doc_id: 349794 cord_uid: mhviub6e file: cache/cord-346978-ubkqny8j.json key: cord-346978-ubkqny8j authors: Ranoa, Diana Rose E.; Holland, Robin L.; Alnaji, Fadi G.; Green, Kelsie J.; Wang, Leyi; Brooke, Christopher B.; Burke, Martin D.; Fan, Timothy M.; Hergenrother, Paul J. title: Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction date: 2020-06-18 journal: bioRxiv DOI: 10.1101/2020.06.18.159434 sha: doc_id: 346978 cord_uid: ubkqny8j file: cache/cord-350627-4pgish5x.json key: cord-350627-4pgish5x authors: Zhao, Yu; Zhao, Zixian; Wang, Yujia; Zhou, Yueqing; Ma, Yu; Zuo, Wei title: Single-cell RNA expression profiling of ACE2,thereceptor of SARS-CoV-2 date: 2020-01-26 journal: bioRxiv DOI: 10.1101/2020.01.26.919985 sha: doc_id: 350627 cord_uid: 4pgish5x file: cache/cord-349364-vert186n.json key: cord-349364-vert186n authors: Márquez-López, Cristina; Roche-Molina, Marta; García-Quintáns, Nieves; Sacristán, Silvia; Siniscalco, David; González-Guerra, Andrés; Camafeita, Emilio; Lytvyn, Mariya; Guillen, María I.; Sanz-Rosa, David; Martín-Pérez, Daniel; Sánchez-Ramos, Cristina; García, Ricardo; Bernal, Juan A. title: SARS-CoV-2 protein Nsp1 alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy-related PKP2 mutant date: 2020-09-14 journal: bioRxiv DOI: 10.1101/2020.09.14.296178 sha: doc_id: 349364 cord_uid: vert186n file: cache/cord-350286-n7ylgqfu.json key: cord-350286-n7ylgqfu authors: Giri, Rajanish; Bhardwaj, Taniya; Shegane, Meenakshi; Gehi, Bhuvaneshwari R.; Kumar, Prateek; Gadhave, Kundlik; Oldfield, Christopher J.; Uversky, Vladimir N. title: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date: 2020-04-03 journal: bioRxiv DOI: 10.1101/2020.03.13.990598 sha: doc_id: 350286 cord_uid: n7ylgqfu file: cache/cord-348159-v5hrcl5k.json key: cord-348159-v5hrcl5k authors: Sang, Eric R.; Tian, Yun; Miller, Laura C.; Sang, Yongming title: Epigenetic Evolution of ACE2 and IL-6 Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates date: 2020-09-10 journal: bioRxiv DOI: 10.1101/2020.09.09.273268 sha: doc_id: 348159 cord_uid: v5hrcl5k file: cache/cord-349684-2tioh80m.json key: cord-349684-2tioh80m authors: Pezzotti, Giuseppe; Ohgitani, Eriko; Shin-Ya, Masaharu; Adachi, Tetsuya; Marin, Elia; Boschetto, Francesco; Zhu, Wenliang; Mazda, Osam title: Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride date: 2020-06-20 journal: bioRxiv DOI: 10.1101/2020.06.19.159970 sha: doc_id: 349684 cord_uid: 2tioh80m file: cache/cord-349015-5oisrm5s.json key: cord-349015-5oisrm5s authors: Liu, Zhe; Zheng, Huanying; Yuan, Runyu; Li, Mingyue; Lin, Huifang; Peng, Jingju; Xiong, Qianlin; Sun, Jiufeng; Li, Baisheng; Wu, Jie; Hulswit, Ruben J.G.; Bowden, Thomas A.; Rambaut, Andrew; Loman, Nick; Pybus, Oliver G; Ke, Changwen; Lu, Jing title: Identification of a common deletion in the spike protein of SARS-CoV-2 date: 2020-04-02 journal: bioRxiv DOI: 10.1101/2020.03.31.015941 sha: doc_id: 349015 cord_uid: 5oisrm5s file: cache/cord-351321-6d2mn5ok.json key: cord-351321-6d2mn5ok authors: Gouveia, Duarte; Miotello, Guylaine; Gallais, Fabrice; Gaillard, Jean-Charles; Debroas, Stéphanie; Bellanger, Laurent; Lavigne, Jean-Philippe; Sotto, Albert; Grenga, Lucia; Pible, Olivier; Armengaud, Jean title: Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window date: 2020-06-19 journal: bioRxiv DOI: 10.1101/2020.06.19.161000 sha: doc_id: 351321 cord_uid: 6d2mn5ok file: cache/cord-350935-p6euuop3.json key: cord-350935-p6euuop3 authors: Doğan, Tunca; Atas, Heval; Joshi, Vishal; Atakan, Ahmet; Rifaioglu, Ahmet Sureyya; Nalbat, Esra; Nightingale, Andrew; Saidi, Rabie; Volynkin, Vladimir; Zellner, Hermann; Cetin-Atalay, Rengul; Martin, Maria; Atalay, Volkan title: CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date: 2020-09-15 journal: bioRxiv DOI: 10.1101/2020.09.14.296889 sha: doc_id: 350935 cord_uid: p6euuop3 file: cache/cord-351559-az4pgi9k.json key: cord-351559-az4pgi9k authors: Turjya, Rafeed Rahman; Khan, Md. Abdullah-Al-Kamran; Islam, Abul Bashar Mir Md. Khademul title: Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date: 2020-06-29 journal: bioRxiv DOI: 10.1101/2020.06.29.177204 sha: doc_id: 351559 cord_uid: az4pgi9k file: cache/cord-353161-mtq6yh25.json key: cord-353161-mtq6yh25 authors: Rodrigues, João PGLM; Barrera-Vilarmau, Susana; Teixeira, João MC; Seckel, Elizabeth; Kastritis, Panagiotis; Levitt, Michael title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling date: 2020-06-05 journal: bioRxiv DOI: 10.1101/2020.06.05.136861 sha: doc_id: 353161 cord_uid: mtq6yh25 file: cache/cord-350558-qfdp4ov9.json key: cord-350558-qfdp4ov9 authors: Shaban, Mohammed Samer; Müller, Christin; Mayr-Buro, Christin; Weiser, Hendrik; Albert, Benadict Vincent; Weber, Axel; Linne, Uwe; Hain, Torsten; Babayev, Ilya; Karl, Nadja; Hofmann, Nina; Becker, Stephan; Herold, Susanne; Schmitz, M. Lienhard; Ziebuhr, John; Kracht, Michael title: Inhibiting coronavirus replication in cultured cells by chemical ER stress date: 2020-08-26 journal: bioRxiv DOI: 10.1101/2020.08.26.266304 sha: doc_id: 350558 cord_uid: qfdp4ov9 file: cache/cord-351472-ch004jxy.json key: cord-351472-ch004jxy authors: Vashi, Yoya; Jagrit, Vipin; Kumar, Sachin title: Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens date: 2020-04-10 journal: bioRxiv DOI: 10.1101/2020.04.08.013516 sha: doc_id: 351472 cord_uid: ch004jxy file: cache/cord-350821-0qfoc553.json key: cord-350821-0qfoc553 authors: Jahromi, Reza; Mogharab, Vahid; Jahromi, Hossein; Avazpour, Arezoo title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 date: 2020-06-01 journal: bioRxiv DOI: 10.1101/2020.05.29.124107 sha: doc_id: 350821 cord_uid: 0qfoc553 file: cache/cord-353554-98uzivsk.json key: cord-353554-98uzivsk authors: Zhang, Zheng; Zhu, Zhaozhong; Chen, Wenjun; Cai, Zena; Xu, Beibei; Tan, Zhiying; Wu, Aiping; Ge, Xingyi; Guo, Xinhong; Tan, Zhongyang; Xia, Zanxian; Zhu, Haizhen; Jiang, Taijiao; Peng, Yousong title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors date: 2018-03-08 journal: bioRxiv DOI: 10.1101/271171 sha: doc_id: 353554 cord_uid: 98uzivsk file: cache/cord-352073-rdhjj72g.json key: cord-352073-rdhjj72g authors: Taniwaki, S.A; Silva, S.O.S; Santana-Clavijo, N.F; Conselheiro, J. A; Barone, G.T; Menezes, A.A.R; Pereira, E.S; Brandão, P.E title: Resource optimization in COVID-19 diagnosis date: 2020-06-26 journal: bioRxiv DOI: 10.1101/2020.06.25.172528 sha: doc_id: 352073 cord_uid: rdhjj72g file: cache/cord-353911-hp6s6ebh.json key: cord-353911-hp6s6ebh authors: Petráš, Marek; Lesný, Petr; Musil, Jan; Limberková, Radomíra; Pátíková, Alžběta; Jirsa, Milan; Krsek, Daniel; Březovský, Pavel; Koladiya, Abhishek; Vaníková, Šárka; Macková, Barbora; Jírová, Dagmar; Krijt, Matyáš; Králová Lesná, Ivana; Adámková, Věra title: Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein date: 2020-11-03 journal: bioRxiv DOI: 10.1101/2020.11.03.366641 sha: doc_id: 353911 cord_uid: hp6s6ebh file: cache/cord-350817-tmszrtju.json key: cord-350817-tmszrtju authors: Hoepel, Willianne; Chen, Hung-Jen; Allahverdiyeva, Sona; Manz, Xue; Aman, Jurjan; Bonta, Peter; Brouwer, Philip; de Taeye, Steven; Caniels, Tom; van der Straten, Karlijn; Golebski, Korneliusz; Griffith, Guillermo; Jonkers, René; Larsen, Mads; Linty, Federica; Neele, Annette; Nouta, Jan; van Baarle, Frank; van Drunen, Cornelis; Vlaar, Alexander; de Bree, Godelieve; Sanders, Rogier; Willemsen, Lisa; Wuhrer, Manfred; Bogaard, Harm Jan; van Gils, Marit; Vidarsson, Gestur; de Winther, Menno; den Dunnen, Jeroen title: Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses date: 2020-07-13 journal: bioRxiv DOI: 10.1101/2020.07.13.190140 sha: doc_id: 350817 cord_uid: tmszrtju file: cache/cord-353129-ivbf4kuq.json key: cord-353129-ivbf4kuq authors: Faryami, Ahmad; Harris, Carolyn A title: Open source 3D printed Ventilation Device date: 2020-05-22 journal: bioRxiv DOI: 10.1101/2020.05.21.108043 sha: doc_id: 353129 cord_uid: ivbf4kuq file: cache/cord-352943-ztonp62x.json key: cord-352943-ztonp62x authors: Nagpal, Sunil; Srivastava, Divyanshu; Mande, Sharmila S. title: What if we perceive SARS-CoV-2 genomes as documents? Topic modelling using Latent Dirichlet Allocation to identify mutation signatures and classify SARS-CoV-2 genomes date: 2020-08-20 journal: bioRxiv DOI: 10.1101/2020.08.20.258772 sha: doc_id: 352943 cord_uid: ztonp62x file: cache/cord-353099-38bz0acw.json key: cord-353099-38bz0acw authors: Tang, Mei San; Case, James Brett; Franks, Caroline E.; Chen, Rita E.; Anderson, Neil W.; Henderson, Jeffrey P.; Diamond, Michael S.; Gronowski, Ann M.; Farnsworth, Christopher W. title: Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays date: 2020-07-02 journal: bioRxiv DOI: 10.1101/2020.07.01.182220 sha: doc_id: 353099 cord_uid: 38bz0acw file: cache/cord-353742-k4gxww2c.json key: cord-353742-k4gxww2c authors: Arévalo, AP; Pagotto, R; Pórfido, J; Daghero, H; Segovia, M; Yamasaki, K; Varela, B; Hill, M; Verdes, JM; Duhalde Vega, M; Bollati-Fogolín, M; Crispo, M title: Ivermectin reduces coronavirus infection in vivo: a mouse experimental model date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.11.02.363242 sha: doc_id: 353742 cord_uid: k4gxww2c file: cache/cord-353209-qkhfp66l.json key: cord-353209-qkhfp66l authors: Steiner, Daniel J.; Cognetti, John S.; Luta, Ethan P.; Klose, Alanna M.; Bucukovski, Joseph; Bryan, Michael R.; Schmuke, Jon J.; Nguyen-Contant, Phuong; Sangster, Mark Y.; Topham, David J.; Miller, Benjamin L. title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date: 2020-06-16 journal: bioRxiv DOI: 10.1101/2020.06.15.153064 sha: doc_id: 353209 cord_uid: qkhfp66l file: cache/cord-353877-wzndpcq3.json key: cord-353877-wzndpcq3 authors: Albagi, Sahar Obi Abd; Al-Nour, Mosab Yahya; Elhag, Mustafa; Abdelihalim, Asaad Tageldein Idris; Haroun, Esraa Musa; Essa, Mohammed Elmujtba Adam; Abubaker, Mustafa; Hassan, Mohammed A. title: A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach date: 2020-05-20 journal: bioRxiv DOI: 10.1101/2020.05.20.106351 sha: doc_id: 353877 cord_uid: wzndpcq3 file: cache/cord-355728-wivk0bm0.json key: cord-355728-wivk0bm0 authors: Schoof, Michael; Faust, Bryan; Saunders, Reuben A.; Sangwan, Smriti; Rezelj, Veronica; Hoppe, Nick; Boone, Morgane; Billesbølle, Christian B.; Puchades, Cristina; Azumaya, Caleigh M.; Kratochvil, Huong T.; Zimanyi, Marcell; Deshpande, Ishan; Liang, Jiahao; Dickinson, Sasha; Nguyen, Henry C.; Chio, Cynthia M.; Merz, Gregory E.; Thompson, Michael C.; Diwanji, Devan; Schaefer, Kaitlin; Anand, Aditya A.; Dobzinski, Niv; Zha, Beth Shoshana; Simoneau, Camille R.; Leon, Kristoffer; White, Kris M.; Chio, Un Seng; Gupta, Meghna; Jin, Mingliang; Li, Fei; Liu, Yanxin; Zhang, Kaihua; Bulkley, David; Sun, Ming; Smith, Amber M.; Rizo, Alexandrea N.; Moss, Frank; Brilot, Axel F.; Pourmal, Sergei; Trenker, Raphael; Pospiech, Thomas; Gupta, Sayan; Barsi-Rhyne, Benjamin; Belyy, Vladislav; Barile-Hill, Andrew W.; Nock, Silke; Liu, Yuwei; Krogan, Nevan J.; Ralston, Corie Y.; Swaney, Danielle L.; García-Sastre, Adolfo; Ott, Melanie; Vignuzzi, Marco; Walter, Peter; Manglik, Aashish title: An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation date: 2020-08-17 journal: bioRxiv DOI: 10.1101/2020.08.08.238469 sha: doc_id: 355728 cord_uid: wivk0bm0 file: cache/cord-355811-aq7p1uxo.json key: cord-355811-aq7p1uxo authors: Węglarz-Tomczak, Ewelina; Tomczak, Jakub M.; Giurg, Mirosław; Burda-Grabowska, Małgorzata; Brul, Stanley title: Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds date: 2020-05-21 journal: bioRxiv DOI: 10.1101/2020.05.20.107052 sha: doc_id: 355811 cord_uid: aq7p1uxo file: cache/cord-356005-zhwtlik6.json key: cord-356005-zhwtlik6 authors: Yazhini, Arangasamy; Sidhanta, Das Swayam Prakash; Srinivasan, Narayanaswamy title: D614G substitution enhances the stability of trimeric SARS-CoV-2 spike protein date: 2020-11-02 journal: bioRxiv DOI: 10.1101/2020.11.02.364273 sha: doc_id: 356005 cord_uid: zhwtlik6 file: cache/cord-354725-lqio7l8k.json key: cord-354725-lqio7l8k authors: Arumugam, Arunkumar; Faron, Matthew L.; Yu, Peter; Markham, Cole; Wong, Season title: A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings date: 2020-04-30 journal: bioRxiv DOI: 10.1101/2020.04.29.069591 sha: doc_id: 354725 cord_uid: lqio7l8k file: cache/cord-355758-tk7eturq.json key: cord-355758-tk7eturq authors: Berrio, Alejandro; Gartner, Valerie; Wray, Gregory A title: Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function date: 2020-09-22 journal: bioRxiv DOI: 10.1101/2020.09.16.300038 sha: doc_id: 355758 cord_uid: tk7eturq file: cache/cord-351011-v4zmksio.json key: cord-351011-v4zmksio authors: Golden, Joseph W.; Cline, Curtis R.; Zeng, Xiankun; Garrison, Aura R.; Carey, Brian D.; Mucker, Eric M.; White, Lauren E.; Shamblin, Joshua D.; Brocato, Rebecca L.; Liu, Jun; Babka, April M.; Rauch, Hypaitia B.; Smith, Jeffrey M.; Hollidge, Bradley S.; Fitzpatrick, Collin; Badger, Catherine V.; Hooper, Jay W. title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date: 2020-07-09 journal: bioRxiv DOI: 10.1101/2020.07.09.195230 sha: doc_id: 351011 cord_uid: v4zmksio file: cache/cord-356090-oj3d9ail.json key: cord-356090-oj3d9ail authors: Gorgun, D.; Lihan, M.; Kapoor, K.; Tajkhorshid, E. title: Binding Mode of SARS-CoV2 Fusion Peptide to Human Cellular Membrane date: 2020-10-27 journal: bioRxiv DOI: 10.1101/2020.10.27.357350 sha: doc_id: 356090 cord_uid: oj3d9ail file: cache/cord-354868-pqn59ojj.json key: cord-354868-pqn59ojj authors: Yao, Hebang; Cai, Hongmin; Li, Tingting; Zhou, Bingjie; Qin, Wenming; Lavillette, Dimitri; Li, Dianfan title: A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2 date: 2020-09-25 journal: bioRxiv DOI: 10.1101/2020.09.24.312595 sha: doc_id: 354868 cord_uid: pqn59ojj file: cache/cord-353777-t8q99tlq.json key: cord-353777-t8q99tlq authors: Jia, Yong; Shen, Gangxu; Zhang, Yujuan; Huang, Keng-Shiang; Ho, Hsing-Ying; Hor, Wei-Shio; Yang, Chih-Hui; Li, Chengdao; Wang, Wei-Lung title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date: 2020-04-11 journal: bioRxiv DOI: 10.1101/2020.04.09.034942 sha: doc_id: 353777 cord_uid: t8q99tlq file: cache/cord-354315-yfn9vaan.json key: cord-354315-yfn9vaan authors: Meirson, Tomer; Bomze, David; Markel, Gal title: Structural basis of SARS-CoV-2 spike protein induced by ACE2 date: 2020-05-24 journal: bioRxiv DOI: 10.1101/2020.05.24.113175 sha: doc_id: 354315 cord_uid: yfn9vaan file: cache/cord-353731-7xn7m662.json key: cord-353731-7xn7m662 authors: Heaton, Brook E.; Trimarco, Joseph D.; Hamele, Cait E.; Harding, Alfred T.; Tata, Aleksandra; Zhu, Xinyu; Tata, Purushothama Rao; Smith, Clare M.; Heaton, Nicholas S. title: SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2 date: 2020-08-18 journal: bioRxiv DOI: 10.1101/2020.08.14.251207 sha: doc_id: 353731 cord_uid: 7xn7m662 file: cache/cord-356264-q0yqnlyl.json key: cord-356264-q0yqnlyl authors: Armijos-Jaramillo, Vinicio; Yeager, Justin; Muslin, Claire; Perez-Castillo, Yunierkis title: SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability date: 2020-03-23 journal: bioRxiv DOI: 10.1101/2020.03.21.001933 sha: doc_id: 356264 cord_uid: q0yqnlyl file: cache/cord-355397-y69bk5jc.json key: cord-355397-y69bk5jc authors: Caruso, Ícaro P.; Sanches, Karoline; Da Poian, Andrea T.; Pinheiro, Anderson S.; Almeida, Fabio C. L. title: Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism date: 2020-09-06 journal: bioRxiv DOI: 10.1101/2020.08.24.264465 sha: doc_id: 355397 cord_uid: y69bk5jc Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named journal-biorxiv-cord parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64463 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64559 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64716 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65223 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64555 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64557 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64646 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64985 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65117 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65026 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65207 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64921 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65178 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65395 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65133 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65212 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 95. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65147 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 94. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65444 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 93. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 92. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 64544 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65238 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 65061 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66370 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66366 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66466 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 91. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66382 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66394 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66428 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66472 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66467 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66427 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66425 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 90. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 84. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66449 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66469 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66546 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67610 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68535 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66364 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66383 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66509 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67305 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66468 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67076 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67614 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 85. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 67470 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68505 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68641 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66451 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66424 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66730 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68349 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 88. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68845 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68668 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68776 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68771 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 70464 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable parallel: Warning: No more processes: Decreasing number of running jobs to 89. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 66543 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 68487 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 71002 Aborted $FILE2BIB "$FILE" > "$OUTPUT" /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-102321-csdezu6y author: Booeshaghi, A. Sina title: Normalization of single-cell RNA-seq counts by log(x+1)* or log(1+x)* date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-102321-csdezu6y.txt cache: ./cache/cord-102321-csdezu6y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-102321-csdezu6y.txt' /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-102151-26lumewy author: Cox, Robert M. title: Therapeutic Targeting of Measles Virus Polymerase with ERDRP-0519 Suppresses All RNA Synthesis Activity date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-102151-26lumewy.txt cache: ./cache/cord-102151-26lumewy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-102151-26lumewy.txt' /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable === file2bib.sh === id: cord-102199-mc6zruyx author: Toksvang, Linea Natalie title: Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review date: 2019-01-30 pages: extension: .txt txt: ./txt/cord-102199-mc6zruyx.txt cache: ./cache/cord-102199-mc6zruyx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102199-mc6zruyx.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordwrd2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes === file2bib.sh === id: cord-102364-t5bt2eb4 author: Yao, Dehui title: Human H-ferritin presenting RBM of spike glycoprotein as potential vaccine of SARS-CoV-2 date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-102364-t5bt2eb4.txt cache: ./cache/cord-102364-t5bt2eb4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102364-t5bt2eb4.txt' /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordpos2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/cordent2carrel.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-102530-wetqqt2i author: Brandell, Ellen E. title: The rise of disease ecology date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-102530-wetqqt2i.txt cache: ./cache/cord-102530-wetqqt2i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102530-wetqqt2i.txt' === file2bib.sh === id: cord-102336-ex3zlq38 author: De Wijngaert, Brent title: Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-102336-ex3zlq38.txt cache: ./cache/cord-102336-ex3zlq38.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102336-ex3zlq38.txt' === file2bib.sh === id: cord-102383-m5ahicqb author: Romano, Alessandra title: Energy dynamics for systemic configurations of virus-host co-evolution date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-102383-m5ahicqb.txt cache: ./cache/cord-102383-m5ahicqb.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102383-m5ahicqb.txt' === file2bib.sh === id: cord-102219-d3gkfo7s author: Perzel Mandell, Kira A. title: Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date: 2019-10-30 pages: extension: .txt txt: ./txt/cord-102219-d3gkfo7s.txt cache: ./cache/cord-102219-d3gkfo7s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102219-d3gkfo7s.txt' === file2bib.sh === id: cord-102270-rfhtlodc author: Azhar, Mohd. title: Rapid, field-deployable nucleobase detection and identification using FnCas9 date: 2020-04-21 pages: extension: .txt txt: ./txt/cord-102270-rfhtlodc.txt cache: ./cache/cord-102270-rfhtlodc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102270-rfhtlodc.txt' === file2bib.sh === id: cord-102350-e1vc2q4j author: Yoon, Hye-Jin title: Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-102350-e1vc2q4j.txt cache: ./cache/cord-102350-e1vc2q4j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-102350-e1vc2q4j.txt' === file2bib.sh === id: cord-102279-ena1usqv author: Long, Rory K. M. title: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-102279-ena1usqv.txt cache: ./cache/cord-102279-ena1usqv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102279-ena1usqv.txt' === file2bib.sh === id: cord-102178-ju826pao author: Carey, Clayton M. title: Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis date: 2020-03-30 pages: extension: .txt txt: ./txt/cord-102178-ju826pao.txt cache: ./cache/cord-102178-ju826pao.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102178-ju826pao.txt' === file2bib.sh === id: cord-102704-wfuzk2dp author: Meza, Diana K. title: Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-102704-wfuzk2dp.txt cache: ./cache/cord-102704-wfuzk2dp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102704-wfuzk2dp.txt' === file2bib.sh === id: cord-102763-tc1z0nm9 author: Zhang, Yuan title: IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-102763-tc1z0nm9.txt cache: ./cache/cord-102763-tc1z0nm9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102763-tc1z0nm9.txt' === file2bib.sh === id: cord-102729-b1q7gbd6 author: Mickael, Alexandra title: Asip (Agouti-signaling protein) aggression gene regulate auditory processing genes in mice date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-102729-b1q7gbd6.txt cache: ./cache/cord-102729-b1q7gbd6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102729-b1q7gbd6.txt' === file2bib.sh === id: cord-102412-cnlvyey4 author: Tekman, Mehmet title: A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-102412-cnlvyey4.txt cache: ./cache/cord-102412-cnlvyey4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102412-cnlvyey4.txt' === file2bib.sh === id: cord-102918-bkyk7or9 author: Burns, C. Sean title: Methodological Issues with Search in MEDLINE: A Longitudinal Query Analysis date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-102918-bkyk7or9.txt cache: ./cache/cord-102918-bkyk7or9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102918-bkyk7or9.txt' === file2bib.sh === Traceback (most recent call last): File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2646, in get_loc return self._engine.get_loc(key) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-193356-hqbstgg7' During handling of the above exception, another exception occurred: Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/file2bib.py", line 64, in if ( bibliographics.loc[ escape ,'author'] ) : author = bibliographics.loc[ escape,'author'] File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1762, in __getitem__ return self._getitem_tuple(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1272, in _getitem_tuple return self._getitem_lowerdim(tup) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1389, in _getitem_lowerdim section = self._getitem_axis(key, axis=i) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 1965, in _getitem_axis return self._get_label(key, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexing.py", line 625, in _get_label return self.obj._xs(label, axis=axis) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/generic.py", line 3537, in xs loc = self.index.get_loc(key) File "/data-disk/python/lib/python3.8/site-packages/pandas/core/indexes/base.py", line 2648, in get_loc return self._engine.get_loc(self._maybe_cast_indexer(key)) File "pandas/_libs/index.pyx", line 111, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/index.pyx", line 138, in pandas._libs.index.IndexEngine.get_loc File "pandas/_libs/hashtable_class_helper.pxi", line 1619, in pandas._libs.hashtable.PyObjectHashTable.get_item File "pandas/_libs/hashtable_class_helper.pxi", line 1627, in pandas._libs.hashtable.PyObjectHashTable.get_item KeyError: 'cord-193356-hqbstgg7' === file2bib.sh === id: cord-102968-mhawyect author: Desirò, Daniel title: SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structural RNAs date: 2018-09-23 pages: extension: .txt txt: ./txt/cord-102968-mhawyect.txt cache: ./cache/cord-102968-mhawyect.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102968-mhawyect.txt' === file2bib.sh === id: cord-102458-7sssm3zk author: Milanez-Almeida, Pedro title: Blood gene expression-based prediction of lethality after respiratory infection by influenza A virus in mice date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-102458-7sssm3zk.txt cache: ./cache/cord-102458-7sssm3zk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102458-7sssm3zk.txt' === file2bib.sh === id: cord-102892-nt1zoktv author: Sweeney, Blake A. title: R2DT: computational framework for template-based RNA secondary structure visualisation across non-coding RNA types date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-102892-nt1zoktv.txt cache: ./cache/cord-102892-nt1zoktv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102892-nt1zoktv.txt' === file2bib.sh === id: cord-102967-dx0tg077 author: Mahajan, Lakshmi S. title: Mapping RNA dependent RNA polymerase activity and immune gene expression using PRO-seq date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-102967-dx0tg077.txt cache: ./cache/cord-102967-dx0tg077.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102967-dx0tg077.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-102916-t2lcd300 author: Cai, Guoshuai title: SCANNER: A Web Resource for Annotation, Visualization and Sharing of Single Cell RNA-seq Data date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-102916-t2lcd300.txt cache: ./cache/cord-102916-t2lcd300.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102916-t2lcd300.txt' === file2bib.sh === id: cord-103046-w8bm4p44 author: Suarez, David L. title: Lack of susceptibility of poultry to SARS-CoV-2 and MERS-CoV date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-103046-w8bm4p44.txt cache: ./cache/cord-103046-w8bm4p44.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103046-w8bm4p44.txt' === file2bib.sh === id: cord-102886-oo7q05ml author: Gomes, Fabio M. title: “Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes” date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-102886-oo7q05ml.txt cache: ./cache/cord-102886-oo7q05ml.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102886-oo7q05ml.txt' === file2bib.sh === id: cord-103294-1lrfna4v author: Northrop, Amanda C. title: Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem date: 2020-05-02 pages: extension: .txt txt: ./txt/cord-103294-1lrfna4v.txt cache: ./cache/cord-103294-1lrfna4v.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103294-1lrfna4v.txt' === file2bib.sh === id: cord-102551-8igfuaw2 author: Boonyaratanakornkit, Jim title: Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-102551-8igfuaw2.txt cache: ./cache/cord-102551-8igfuaw2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102551-8igfuaw2.txt' === file2bib.sh === id: cord-102570-lpwwlrqm author: Fenn, Gareth D. title: Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase) date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-102570-lpwwlrqm.txt cache: ./cache/cord-102570-lpwwlrqm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102570-lpwwlrqm.txt' === file2bib.sh === id: cord-102905-rlee32x7 author: Leis, Jonathan title: Ilaprazole and other novel prazole-based compounds that bind Tsg101 inhibit viral budding of HSV-1/2 and HIV from cells date: 2020-05-04 pages: extension: .txt txt: ./txt/cord-102905-rlee32x7.txt cache: ./cache/cord-102905-rlee32x7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102905-rlee32x7.txt' === file2bib.sh === id: cord-102935-cx3elpb8 author: Hassani-Pak, Keywan title: KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-102935-cx3elpb8.txt cache: ./cache/cord-102935-cx3elpb8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102935-cx3elpb8.txt' === file2bib.sh === id: cord-102976-cic1gxrk author: Patel, Roosheel S. title: Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells date: 2020-05-07 pages: extension: .txt txt: ./txt/cord-102976-cic1gxrk.txt cache: ./cache/cord-102976-cic1gxrk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102976-cic1gxrk.txt' === file2bib.sh === id: cord-103055-071a5b0x author: Rathbun, LI title: PLK1- and PLK4-mediated asymmetric mitotic centrosome size and positioning in the early zebrafish embryo date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-103055-071a5b0x.txt cache: ./cache/cord-103055-071a5b0x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103055-071a5b0x.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-102811-jlr4vb4u author: Baumeister, Sebastian E title: Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study date: 2019-10-29 pages: extension: .txt txt: ./txt/cord-102811-jlr4vb4u.txt cache: ./cache/cord-102811-jlr4vb4u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102811-jlr4vb4u.txt' === file2bib.sh === id: cord-103181-my4n0vye author: Valle-Casuso, José Carlos title: Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors date: 2020-04-10 pages: extension: .txt txt: ./txt/cord-103181-my4n0vye.txt cache: ./cache/cord-103181-my4n0vye.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103181-my4n0vye.txt' === file2bib.sh === id: cord-103077-sh4w2mye author: Lu, Shuai title: Leveraging Sequential and Spatial Neighbors Information by Using CNNs Linked With GCNs for Paratope Prediction date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-103077-sh4w2mye.txt cache: ./cache/cord-103077-sh4w2mye.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103077-sh4w2mye.txt' === file2bib.sh === id: cord-103112-m6cg67lz author: Schloer, Sebastian title: Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-103112-m6cg67lz.txt cache: ./cache/cord-103112-m6cg67lz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103112-m6cg67lz.txt' === file2bib.sh === id: cord-103204-gt6upfri author: Hölzer, Martin title: PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-103204-gt6upfri.txt cache: ./cache/cord-103204-gt6upfri.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103204-gt6upfri.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-102958-q8jamg07 author: Hahka, Taija M. title: Resiniferatoxin (RTX) ameliorates acute respiratory distress syndrome (ARDS) in a rodent model of lung injury date: 2020-09-14 pages: extension: .txt txt: ./txt/cord-102958-q8jamg07.txt cache: ./cache/cord-102958-q8jamg07.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102958-q8jamg07.txt' === file2bib.sh === id: cord-103174-4m3ajc8a author: Okada, Megan title: Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-103174-4m3ajc8a.txt cache: ./cache/cord-103174-4m3ajc8a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103174-4m3ajc8a.txt' === file2bib.sh === id: cord-103208-krann2ir author: Barber-Axthelm, Isaac M title: Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node date: 2020-08-29 pages: extension: .txt txt: ./txt/cord-103208-krann2ir.txt cache: ./cache/cord-103208-krann2ir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103208-krann2ir.txt' === file2bib.sh === id: cord-103187-a255643n author: Mitchell, Evan title: Prophylactic host behaviour discourages pathogen exploitation date: 2019-12-19 pages: extension: .txt txt: ./txt/cord-103187-a255643n.txt cache: ./cache/cord-103187-a255643n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103187-a255643n.txt' === file2bib.sh === id: cord-102920-z5q3wo7v author: Sang, Eric R. title: Integrate Structural Analysis, Isoform Diversity, and Interferon-Inductive Propensity of ACE2 to Refine SARS-CoV2 Susceptibility Prediction in Vertebrates date: 2020-06-28 pages: extension: .txt txt: ./txt/cord-102920-z5q3wo7v.txt cache: ./cache/cord-102920-z5q3wo7v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102920-z5q3wo7v.txt' === file2bib.sh === id: cord-102977-yci9kq6x author: Liu, Haiming title: GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia date: 2019-12-06 pages: extension: .txt txt: ./txt/cord-102977-yci9kq6x.txt cache: ./cache/cord-102977-yci9kq6x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102977-yci9kq6x.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-102908-sr7j8z9c author: Mersmann, Sophia F. title: Learning to count: determining the stoichiometry of bio-molecular complexes using fluorescence microscopy and statistical modelling date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-102908-sr7j8z9c.txt cache: ./cache/cord-102908-sr7j8z9c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102908-sr7j8z9c.txt' === file2bib.sh === id: cord-103180-5hkoeca7 author: Furstenau, Tara N. title: Sample pooling methods for efficient pathogen screening: Practical implications date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-103180-5hkoeca7.txt cache: ./cache/cord-103180-5hkoeca7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103180-5hkoeca7.txt' === file2bib.sh === id: cord-103081-k7ev5qkn author: Janosevic, Danielle title: The orchestrated cellular and molecular responses of the kidney to endotoxin define the sepsis timeline date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-103081-k7ev5qkn.txt cache: ./cache/cord-103081-k7ev5qkn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103081-k7ev5qkn.txt' === file2bib.sh === id: cord-102835-71ome9h8 author: Levinson, Maxwell Adam title: FAIRSCAPE: A Framework for FAIR and Reproducible Biomedical Analytics date: 2020-08-15 pages: extension: .txt txt: ./txt/cord-102835-71ome9h8.txt cache: ./cache/cord-102835-71ome9h8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-102835-71ome9h8.txt' === file2bib.sh === id: cord-103301-v4l9sovt author: Bloom, David C. title: Immunization by replication-competent controlled herpesvirus vectors date: 2018-04-11 pages: extension: .txt txt: ./txt/cord-103301-v4l9sovt.txt cache: ./cache/cord-103301-v4l9sovt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103301-v4l9sovt.txt' === file2bib.sh === id: cord-103271-l9n27ocf author: Carozza, Jacqueline A title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-103271-l9n27ocf.txt cache: ./cache/cord-103271-l9n27ocf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103271-l9n27ocf.txt' === file2bib.sh === id: cord-103343-k4v5ksvq author: Naim, Nikki title: NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-103343-k4v5ksvq.txt cache: ./cache/cord-103343-k4v5ksvq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-103343-k4v5ksvq.txt' === file2bib.sh === id: cord-103460-5thh6syt author: Carlson, Colin J. title: Climate change will drive novel cross-species viral transmission date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-103460-5thh6syt.txt cache: ./cache/cord-103460-5thh6syt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103460-5thh6syt.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-103015-3dxwbmd2 author: Shengjuler, Djoshkun title: The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain date: 2017-08-04 pages: extension: .txt txt: ./txt/cord-103015-3dxwbmd2.txt cache: ./cache/cord-103015-3dxwbmd2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103015-3dxwbmd2.txt' === file2bib.sh === id: cord-103135-nly9vojr author: Fletcher, Nicola F. title: A novel antiviral formulation inhibits a range of enveloped viruses date: 2020-03-30 pages: extension: .txt txt: ./txt/cord-103135-nly9vojr.txt cache: ./cache/cord-103135-nly9vojr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-103135-nly9vojr.txt' === file2bib.sh === id: cord-103157-xe5ccw9j author: Mayer, David title: Developing and Deploying a Scalable Computing Platform to Support MOOC Education in Clinical Data Science date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-103157-xe5ccw9j.txt cache: ./cache/cord-103157-xe5ccw9j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103157-xe5ccw9j.txt' === file2bib.sh === id: cord-103417-2uinislh author: Doi, Hideyuki title: On-site eDNA detection of species using ultra-rapid mobile PCR date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-103417-2uinislh.txt cache: ./cache/cord-103417-2uinislh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103417-2uinislh.txt' === file2bib.sh === id: cord-103497-1ls2dvzy author: Ganier, C title: CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-103497-1ls2dvzy.txt cache: ./cache/cord-103497-1ls2dvzy.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103497-1ls2dvzy.txt' === file2bib.sh === id: cord-103363-efd80dgn author: Mahan, Margaret title: tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports date: 2019-03-21 pages: extension: .txt txt: ./txt/cord-103363-efd80dgn.txt cache: ./cache/cord-103363-efd80dgn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103363-efd80dgn.txt' === file2bib.sh === id: cord-103341-q7yqnvm2 author: MacPherson, Ailene title: A General Birth-Death-Sampling Model for Epidemiology and Macroevolution date: 2020-10-11 pages: extension: .txt txt: ./txt/cord-103341-q7yqnvm2.txt cache: ./cache/cord-103341-q7yqnvm2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103341-q7yqnvm2.txt' === file2bib.sh === id: cord-103408-vhrlrd2c author: Mishra, Preet title: Decision Support Systems based on Scientific Evidence: Bibliometric Networks of Invasive Lantana camara date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-103408-vhrlrd2c.txt cache: ./cache/cord-103408-vhrlrd2c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103408-vhrlrd2c.txt' === file2bib.sh === id: cord-103504-ucqqpra5 author: Zhang, Zhe title: The conserved ER-transmembrane protein TMEM39 coordinates with COPII to promote collagen secretion and prevent ER stress date: 2020-09-20 pages: extension: .txt txt: ./txt/cord-103504-ucqqpra5.txt cache: ./cache/cord-103504-ucqqpra5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103504-ucqqpra5.txt' === file2bib.sh === id: cord-102964-zh737cjk author: Ferraro, Francesco title: Modulation of endothelial organelle size as an antithrombotic strategy date: 2020-05-17 pages: extension: .txt txt: ./txt/cord-102964-zh737cjk.txt cache: ./cache/cord-102964-zh737cjk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102964-zh737cjk.txt' === file2bib.sh === id: cord-103350-jj9pc4a6 author: Tang, Pingtao title: An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-103350-jj9pc4a6.txt cache: ./cache/cord-103350-jj9pc4a6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103350-jj9pc4a6.txt' === file2bib.sh === id: cord-103345-v555a2ll author: Taylor, Adrian title: The novel roles of choline transporter-like 1 and 2 in ethanolamine transport date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-103345-v555a2ll.txt cache: ./cache/cord-103345-v555a2ll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103345-v555a2ll.txt' === file2bib.sh === id: cord-103462-z3d9lcar author: Wang, Shiyu title: CD4+ T cell subsets present stable relationships in their T cell receptor repertoires date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-103462-z3d9lcar.txt cache: ./cache/cord-103462-z3d9lcar.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103462-z3d9lcar.txt' === file2bib.sh === id: cord-103249-k35o3gxe author: Johannsen, Leif title: Robotic light touch assists human balance control during maximum forward reaching date: 2019-11-20 pages: extension: .txt txt: ./txt/cord-103249-k35o3gxe.txt cache: ./cache/cord-103249-k35o3gxe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103249-k35o3gxe.txt' === file2bib.sh === id: cord-103509-hynnba03 author: Wong, Ten-Tsao title: A self-assembled protein nanoparticle serving as a one-shot vaccine carrier date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-103509-hynnba03.txt cache: ./cache/cord-103509-hynnba03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103509-hynnba03.txt' === file2bib.sh === id: cord-102749-tgka0pl0 author: Tovo, Anna title: Taxonomic classification method for metagenomics based on core protein families with Core-Kaiju date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-102749-tgka0pl0.txt cache: ./cache/cord-102749-tgka0pl0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-102749-tgka0pl0.txt' === file2bib.sh === id: cord-103320-2rpr7aph author: Bhandari, Bikash K. title: Solubility-Weighted Index: fast and accurate prediction of protein solubility date: 2020-03-26 pages: extension: .txt txt: ./txt/cord-103320-2rpr7aph.txt cache: ./cache/cord-103320-2rpr7aph.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103320-2rpr7aph.txt' === file2bib.sh === id: cord-102931-vxkbctiz author: Mao, Kai title: Induction of RNA interference by C. elegans mitochondrial dysfunction via the DRH-1/RIG-I homologue RNA helicase and the EOL-1/RNA decapping enzyme date: 2020-06-06 pages: extension: .txt txt: ./txt/cord-102931-vxkbctiz.txt cache: ./cache/cord-102931-vxkbctiz.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-102931-vxkbctiz.txt' === file2bib.sh === id: cord-103085-vf4qyvft author: Seitz, Christian title: Multiscale simulations examining glycan shield effects on drug binding to influenza neuraminidase date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-103085-vf4qyvft.txt cache: ./cache/cord-103085-vf4qyvft.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103085-vf4qyvft.txt' === file2bib.sh === id: cord-103105-iqjksoim author: Marinaik, Chandranaik B. title: Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-103105-iqjksoim.txt cache: ./cache/cord-103105-iqjksoim.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103105-iqjksoim.txt' === file2bib.sh === id: cord-103041-ymr3e60k author: Wu, Yue title: Homeostatic mechanisms regulate distinct aspects of cortical circuit dynamics date: 2019-10-02 pages: extension: .txt txt: ./txt/cord-103041-ymr3e60k.txt cache: ./cache/cord-103041-ymr3e60k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103041-ymr3e60k.txt' === file2bib.sh === id: cord-103176-hfd8ur9a author: Frost, H. Robert title: Variance-adjusted Mahalanobis (VAM): a fast and accurate method for cell-specific gene set scoring date: 2020-02-19 pages: extension: .txt txt: ./txt/cord-103176-hfd8ur9a.txt cache: ./cache/cord-103176-hfd8ur9a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103176-hfd8ur9a.txt' === file2bib.sh === id: cord-103108-vmze2mdx author: Vanheer, Lotte title: Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-103108-vmze2mdx.txt cache: ./cache/cord-103108-vmze2mdx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103108-vmze2mdx.txt' === file2bib.sh === id: cord-103150-e9q8e62v author: Mishra, Shreya title: Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs date: 2020-11-04 pages: extension: .txt txt: ./txt/cord-103150-e9q8e62v.txt cache: ./cache/cord-103150-e9q8e62v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103150-e9q8e62v.txt' === file2bib.sh === id: cord-103029-nc5yf6x4 author: Wichmann, Stefan title: Computational design of genes encoding completely overlapping protein domains: Influence of genetic code and taxonomic rank date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-103029-nc5yf6x4.txt cache: ./cache/cord-103029-nc5yf6x4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103029-nc5yf6x4.txt' === file2bib.sh === id: cord-103163-0rreoh4o author: Smith, Sydni Caet title: Reovirus RNA recombination is sequence directed and generates internally deleted defective genome segments during passage date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-103163-0rreoh4o.txt cache: ./cache/cord-103163-0rreoh4o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103163-0rreoh4o.txt' === file2bib.sh === id: cord-103306-1wc3f1rl author: Sengupta, Sourodip title: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine coronavirus-induced neuroinflammation date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-103306-1wc3f1rl.txt cache: ./cache/cord-103306-1wc3f1rl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103306-1wc3f1rl.txt' === file2bib.sh === id: cord-103465-6udhvl9n author: Schierding, William title: Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date: 2020-04-13 pages: extension: .txt txt: ./txt/cord-103465-6udhvl9n.txt cache: ./cache/cord-103465-6udhvl9n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103465-6udhvl9n.txt' === file2bib.sh === id: cord-103396-jiuqk6kg author: Adler, Paul N. title: Short distance non-autonomy and intercellular transfer of chitin synthase in Drosophila date: 2020-05-26 pages: extension: .txt txt: ./txt/cord-103396-jiuqk6kg.txt cache: ./cache/cord-103396-jiuqk6kg.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103396-jiuqk6kg.txt' === file2bib.sh === id: cord-103430-x6zzuu7v author: Contu, Lara title: Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-103430-x6zzuu7v.txt cache: ./cache/cord-103430-x6zzuu7v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103430-x6zzuu7v.txt' === file2bib.sh === id: cord-103435-yufvt44t author: van Aalst, Marvin title: Constructing and analysing dynamic models with modelbase v1.0 - a software update date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-103435-yufvt44t.txt cache: ./cache/cord-103435-yufvt44t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103435-yufvt44t.txt' === file2bib.sh === id: cord-103358-1hbw3yo3 author: Gisbert-Muñoz, Sandra title: MULTIMAP: Multilingual picture naming test for mapping eloquent areas during awake surgeries date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-103358-1hbw3yo3.txt cache: ./cache/cord-103358-1hbw3yo3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103358-1hbw3yo3.txt' === file2bib.sh === id: cord-103422-ys846i99 author: Xu, Xinhui title: CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-103422-ys846i99.txt cache: ./cache/cord-103422-ys846i99.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103422-ys846i99.txt' === file2bib.sh === id: cord-103511-31njndob author: Broggi, Achille title: Type III interferons disrupt the lung epithelial barrier upon viral recognition date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-103511-31njndob.txt cache: ./cache/cord-103511-31njndob.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103511-31njndob.txt' === file2bib.sh === id: cord-103524-1w9tdhdd author: Hao, Siyuan title: Establishment of a Replicon System for Bourbon Virus and Identification of Small Molecules that Efficiently Inhibit Virus Replication date: 2020-04-25 pages: extension: .txt txt: ./txt/cord-103524-1w9tdhdd.txt cache: ./cache/cord-103524-1w9tdhdd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103524-1w9tdhdd.txt' === file2bib.sh === id: cord-103421-46owvqw8 author: Saunders, Jaclyn K. title: METATRYP v 2.0: Metaproteomic Least Common Ancestor Analysis for Taxonomic Inference Using Specialized Sequence Assemblies - Standalone Software and Web Servers for Marine Microorganisms and Coronaviruses date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-103421-46owvqw8.txt cache: ./cache/cord-103421-46owvqw8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103421-46owvqw8.txt' === file2bib.sh === id: cord-103432-cdmoazrl author: Richardson, Eve title: A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-103432-cdmoazrl.txt cache: ./cache/cord-103432-cdmoazrl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103432-cdmoazrl.txt' === file2bib.sh === id: cord-103567-nh9i28lu author: Vanachayangkul, Pattaraporn title: Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques date: 2020-04-29 pages: extension: .txt txt: ./txt/cord-103567-nh9i28lu.txt cache: ./cache/cord-103567-nh9i28lu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103567-nh9i28lu.txt' === file2bib.sh === id: cord-103554-11avjsqu author: Davies, Jennifer L title: Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles date: 2019-10-17 pages: extension: .txt txt: ./txt/cord-103554-11avjsqu.txt cache: ./cache/cord-103554-11avjsqu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103554-11avjsqu.txt' === file2bib.sh === id: cord-103563-7a3wdduq author: Nunez-Bajo, Estefania title: Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens date: 2020-03-25 pages: extension: .txt txt: ./txt/cord-103563-7a3wdduq.txt cache: ./cache/cord-103563-7a3wdduq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103563-7a3wdduq.txt' === file2bib.sh === id: cord-103542-mf721oa9 author: Mazhari, Ramin title: A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against P. vivax antigens in a multiplexed bead-based assay using Luminex® technology (Bio-Plex® 200 or MAGPIX®) date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-103542-mf721oa9.txt cache: ./cache/cord-103542-mf721oa9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103542-mf721oa9.txt' === file2bib.sh === id: cord-103688-n7hzpbyf author: Wang, Lina title: VirusDIP: Virus Data Integration Platform date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-103688-n7hzpbyf.txt cache: ./cache/cord-103688-n7hzpbyf.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103688-n7hzpbyf.txt' === file2bib.sh === id: cord-103502-asphso2s author: Herrgårdh, Tilda title: An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-103502-asphso2s.txt cache: ./cache/cord-103502-asphso2s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103502-asphso2s.txt' === file2bib.sh === id: cord-103538-vh6ma7k7 author: Smaldino, Paul E. title: Coupled Dynamics of Behavior and Disease Contagion Among Antagonistic Groups date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-103538-vh6ma7k7.txt cache: ./cache/cord-103538-vh6ma7k7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103538-vh6ma7k7.txt' === file2bib.sh === id: cord-103648-g50g17ti author: Wang, Hao-Yuan title: Total synthesis and biological characterization of SR-A3, a ternatin-related eEF1A inhibitor with enhanced cellular residence time date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-103648-g50g17ti.txt cache: ./cache/cord-103648-g50g17ti.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103648-g50g17ti.txt' === file2bib.sh === id: cord-103683-xcsal8vk author: Rafie, K. title: The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-103683-xcsal8vk.txt cache: ./cache/cord-103683-xcsal8vk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103683-xcsal8vk.txt' === file2bib.sh === id: cord-103715-53v1qoyc author: Bauman, Neda title: Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-103715-53v1qoyc.txt cache: ./cache/cord-103715-53v1qoyc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103715-53v1qoyc.txt' === file2bib.sh === id: cord-103618-cl7evbr3 author: Wang, Yingxue title: The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal respiratory infection by influenza A virus at epithelial surfaces date: 2020-05-07 pages: extension: .txt txt: ./txt/cord-103618-cl7evbr3.txt cache: ./cache/cord-103618-cl7evbr3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103618-cl7evbr3.txt' === file2bib.sh === id: cord-103872-yzqic5vt author: Liu, Zhijin title: Global view on virus infection in non-human primates and implication for public health and wildlife conservation date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-103872-yzqic5vt.txt cache: ./cache/cord-103872-yzqic5vt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103872-yzqic5vt.txt' === file2bib.sh === id: cord-103213-oinumv1z author: Kalantar, Katrina L. title: IDseq – An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring date: 2020-04-18 pages: extension: .txt txt: ./txt/cord-103213-oinumv1z.txt cache: ./cache/cord-103213-oinumv1z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 5 resourceName b'cord-103213-oinumv1z.txt' === file2bib.sh === id: cord-103580-6rf1xs0d author: Arokiaraj, Mark Christopher title: A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-103580-6rf1xs0d.txt cache: ./cache/cord-103580-6rf1xs0d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103580-6rf1xs0d.txt' === file2bib.sh === id: cord-103528-3tib5o1m author: Ahmed, Asad title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-103528-3tib5o1m.txt cache: ./cache/cord-103528-3tib5o1m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103528-3tib5o1m.txt' === file2bib.sh === id: cord-103714-06hhlma3 author: Miller, Mariël title: Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-103714-06hhlma3.txt cache: ./cache/cord-103714-06hhlma3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103714-06hhlma3.txt' === file2bib.sh === id: cord-103733-blam1f4c author: Levade, Inès title: Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-103733-blam1f4c.txt cache: ./cache/cord-103733-blam1f4c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103733-blam1f4c.txt' === file2bib.sh === id: cord-103606-5gbk6t6y author: Fettrow, Tyler title: Walking cadence affects the recruitment of the medial-lateral balance mechanisms date: 2019-06-03 pages: extension: .txt txt: ./txt/cord-103606-5gbk6t6y.txt cache: ./cache/cord-103606-5gbk6t6y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103606-5gbk6t6y.txt' === file2bib.sh === id: cord-103523-46hn2249 author: Shaw, Dario R. title: Extracellular electron transfer-dependent anaerobic oxidation of ammonium by anammox bacteria date: 2019-11-26 pages: extension: .txt txt: ./txt/cord-103523-46hn2249.txt cache: ./cache/cord-103523-46hn2249.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103523-46hn2249.txt' === file2bib.sh === id: cord-103739-mmkrwj8t author: Snijder, Eric J. title: A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis date: 2020-03-24 pages: extension: .txt txt: ./txt/cord-103739-mmkrwj8t.txt cache: ./cache/cord-103739-mmkrwj8t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103739-mmkrwj8t.txt' === file2bib.sh === id: cord-103377-j1mmx7k7 author: Karasik, Agnes title: Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-103377-j1mmx7k7.txt cache: ./cache/cord-103377-j1mmx7k7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103377-j1mmx7k7.txt' === file2bib.sh === id: cord-103071-6cgih8o9 author: Mead, Benjamin E. title: High-throughput organoid screening enables engineering of intestinal epithelial composition date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-103071-6cgih8o9.txt cache: ./cache/cord-103071-6cgih8o9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103071-6cgih8o9.txt' === file2bib.sh === id: cord-103448-xa5zgkd3 author: Adachi, Hiroaki title: Jurassic NLR: conserved and dynamic evolutionary features of the atypically ancient immune receptor ZAR1 date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-103448-xa5zgkd3.txt cache: ./cache/cord-103448-xa5zgkd3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103448-xa5zgkd3.txt' === file2bib.sh === id: cord-103568-zesg4atp author: Iacullo, Carly title: Non-selective inhibition of the motor system following unexpected and expected infrequent events date: 2020-03-26 pages: extension: .txt txt: ./txt/cord-103568-zesg4atp.txt cache: ./cache/cord-103568-zesg4atp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103568-zesg4atp.txt' === file2bib.sh === id: cord-103802-mygo3qx0 author: Li, Yanpeng title: Multiple known and a novel parvovirus associated with an outbreak of feline diarrhea and vomiting date: 2020-03-25 pages: extension: .txt txt: ./txt/cord-103802-mygo3qx0.txt cache: ./cache/cord-103802-mygo3qx0.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103802-mygo3qx0.txt' === file2bib.sh === id: cord-103770-4svaq0at author: Ogrodzinski, Martin P. title: Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes date: 2019-10-07 pages: extension: .txt txt: ./txt/cord-103770-4svaq0at.txt cache: ./cache/cord-103770-4svaq0at.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103770-4svaq0at.txt' === file2bib.sh === id: cord-103674-pmbpx162 author: Kalaycı, Salih title: The Linkage among Sea Transportation, Trade Liberalization and Industrial Development in the context of Carbon Dioxide Emissions: An Empirical Investigation from China date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-103674-pmbpx162.txt cache: ./cache/cord-103674-pmbpx162.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103674-pmbpx162.txt' === file2bib.sh === id: cord-103638-n5kpvsvg author: Nguyen, Long T. title: Enhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-103638-n5kpvsvg.txt cache: ./cache/cord-103638-n5kpvsvg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103638-n5kpvsvg.txt' === file2bib.sh === id: cord-103625-p55ew8w7 author: Ramana, Chilakamarti V. title: Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-103625-p55ew8w7.txt cache: ./cache/cord-103625-p55ew8w7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103625-p55ew8w7.txt' === file2bib.sh === id: cord-103735-nil1vv6h author: Alfano, Niccolo title: Non-invasive surveys of mammalian viruses using environmental DNA date: 2020-03-29 pages: extension: .txt txt: ./txt/cord-103735-nil1vv6h.txt cache: ./cache/cord-103735-nil1vv6h.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103735-nil1vv6h.txt' === file2bib.sh === id: cord-103773-1b961lfz author: Kurokawa, Shunji title: In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-103773-1b961lfz.txt cache: ./cache/cord-103773-1b961lfz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103773-1b961lfz.txt' === file2bib.sh === id: cord-103709-86hv27vh author: Zhang, Dong Yan title: Prefusion spike protein stabilization through computational mutagenesis date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-103709-86hv27vh.txt cache: ./cache/cord-103709-86hv27vh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103709-86hv27vh.txt' === file2bib.sh === id: cord-103830-pu6v53oy author: Pichon, Fabien title: Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips date: 2020-05-10 pages: extension: .txt txt: ./txt/cord-103830-pu6v53oy.txt cache: ./cache/cord-103830-pu6v53oy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103830-pu6v53oy.txt' === file2bib.sh === id: cord-103876-2rg2qtdq author: Watkins, Laura C. title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-103876-2rg2qtdq.txt cache: ./cache/cord-103876-2rg2qtdq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103876-2rg2qtdq.txt' === file2bib.sh === id: cord-103517-1itisiup author: Kwesi-Maliepaard, Eliza Mari title: The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells date: 2019-11-18 pages: extension: .txt txt: ./txt/cord-103517-1itisiup.txt cache: ./cache/cord-103517-1itisiup.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103517-1itisiup.txt' === file2bib.sh === id: cord-103592-lkngp2u6 author: Bachmaier, Kurt title: Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-103592-lkngp2u6.txt cache: ./cache/cord-103592-lkngp2u6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103592-lkngp2u6.txt' === file2bib.sh === id: cord-103540-x18pz2uz author: Yellman, Christopher M. title: Precise replacement of Saccharomyces cerevisiae proteasome genes with human orthologs by an integrative targeting method date: 2020-03-26 pages: extension: .txt txt: ./txt/cord-103540-x18pz2uz.txt cache: ./cache/cord-103540-x18pz2uz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103540-x18pz2uz.txt' === file2bib.sh === id: cord-103703-t03r6ny8 author: Nguyen-Tu, Marie-Sophie title: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-103703-t03r6ny8.txt cache: ./cache/cord-103703-t03r6ny8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103703-t03r6ny8.txt' === file2bib.sh === id: cord-103812-ls6zgipi author: Norris, Rachael P. title: Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-103812-ls6zgipi.txt cache: ./cache/cord-103812-ls6zgipi.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103812-ls6zgipi.txt' === file2bib.sh === id: cord-103297-4stnx8dw author: Widrich, Michael title: Modern Hopfield Networks and Attention for Immune Repertoire Classification date: 2020-08-17 pages: extension: .txt txt: ./txt/cord-103297-4stnx8dw.txt cache: ./cache/cord-103297-4stnx8dw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103297-4stnx8dw.txt' === file2bib.sh === id: cord-103869-ii6qi1bp author: Yang, Liu title: Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-103869-ii6qi1bp.txt cache: ./cache/cord-103869-ii6qi1bp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103869-ii6qi1bp.txt' === file2bib.sh === id: cord-103652-yjl7uj2h author: Vickaryous, Nicola title: Remote testing of vitamin D levels across the UK MS population – a case control study date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-103652-yjl7uj2h.txt cache: ./cache/cord-103652-yjl7uj2h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103652-yjl7uj2h.txt' === file2bib.sh === id: cord-103781-bycskjtr author: Mönke, Gregor title: Optimal time frequency analysis for biological data - pyBOAT date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-103781-bycskjtr.txt cache: ./cache/cord-103781-bycskjtr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103781-bycskjtr.txt' === file2bib.sh === id: cord-103654-k02z72gb author: Gamboa Arana, Olga Lucia title: Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-103654-k02z72gb.txt cache: ./cache/cord-103654-k02z72gb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103654-k02z72gb.txt' === file2bib.sh === id: cord-103813-w2sb6h94 author: Schumacher, Garrett J. title: Genetic information insecurity as state of the art date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-103813-w2sb6h94.txt cache: ./cache/cord-103813-w2sb6h94.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103813-w2sb6h94.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 92990 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 93051 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 93034 Aborted $FILE2BIB "$FILE" > "$OUTPUT" parallel: Warning: No more processes: Decreasing number of running jobs to 87. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2adr.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: Resource temporarily unavailable /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-258914-g6pv8zz9 author: Proud, Pamela C. title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-258914-g6pv8zz9.txt cache: ./cache/cord-258914-g6pv8zz9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-258914-g6pv8zz9.txt' parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 86. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. parallel: Warning: No more processes: Decreasing number of running jobs to 83. parallel: Warning: Raising ulimit -u or /etc/security/limits.conf may help. === file2bib.sh === id: cord-103924-mhgnqi80 author: Shin, Donghyuk title: Novel class of OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-103924-mhgnqi80.txt cache: ./cache/cord-103924-mhgnqi80.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103924-mhgnqi80.txt' === file2bib.sh === id: cord-104035-ykyr2gvl author: Ivanov, Mark V. title: Boosting the MS1-only proteomics with machine learning allows 2000 protein identifications in 5-minute proteome analysis date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-104035-ykyr2gvl.txt cache: ./cache/cord-104035-ykyr2gvl.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104035-ykyr2gvl.txt' === file2bib.sh === id: cord-256607-wpywh8c9 author: Itokawa, Kentaro title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-256607-wpywh8c9.txt cache: ./cache/cord-256607-wpywh8c9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-256607-wpywh8c9.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 93771 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 93135 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94245 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 94018 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-104109-k36jya0b author: Das Jana, Indrani title: Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-104109-k36jya0b.txt cache: ./cache/cord-104109-k36jya0b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 47 resourceName b'cord-104109-k36jya0b.txt' === file2bib.sh === id: cord-103868-iwpiti2h author: Harrison, Angela R. title: The Ebola virus interferon antagonist VP24 undergoes active nucleocytoplasmic trafficking date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-103868-iwpiti2h.txt cache: ./cache/cord-103868-iwpiti2h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 31 resourceName b'cord-103868-iwpiti2h.txt' === file2bib.sh === id: cord-255552-k1retwa4 author: Gassen, Nils C. title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-255552-k1retwa4.txt cache: ./cache/cord-255552-k1retwa4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255552-k1retwa4.txt' === file2bib.sh === id: cord-103597-mt0h06y3 author: Muller, Alana title: Neurophysiological Correlates of the Dunning-Kruger Effect date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-103597-mt0h06y3.txt cache: ./cache/cord-103597-mt0h06y3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103597-mt0h06y3.txt' === file2bib.sh === id: cord-255325-tl5fm2yu author: Goletic, Teufik title: Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-255325-tl5fm2yu.txt cache: ./cache/cord-255325-tl5fm2yu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255325-tl5fm2yu.txt' === file2bib.sh === id: cord-262602-on0w55x0 author: Muruato, Antonio E. title: A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-262602-on0w55x0.txt cache: ./cache/cord-262602-on0w55x0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-262602-on0w55x0.txt' === file2bib.sh === id: cord-255069-9xueqdri author: Leary, Shay title: Three adjacent nucleotide changes spanning two residues in SARS-CoV-2 nucleoprotein: possible homologous recombination from the transcription-regulating sequence date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-255069-9xueqdri.txt cache: ./cache/cord-255069-9xueqdri.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255069-9xueqdri.txt' === file2bib.sh === id: cord-255888-znfgh78m author: Fisher, Dale title: Seeding of outbreaks of COVID-19 by contaminated fresh and frozen food date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-255888-znfgh78m.txt cache: ./cache/cord-255888-znfgh78m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255888-znfgh78m.txt' === file2bib.sh === id: cord-258650-aeyf0yu1 author: Joshi, Bhrugesh title: deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 date: 2020-04-02 pages: extension: .txt txt: ./txt/cord-258650-aeyf0yu1.txt cache: ./cache/cord-258650-aeyf0yu1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-258650-aeyf0yu1.txt' /data-disk/reader-compute/reader-cord/bin/txt2urls.sh: fork: retry: No child processes === file2bib.sh === id: cord-261718-zqoggwnk author: Pietschmann, Jan title: Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date: 2020-06-03 pages: extension: .txt txt: ./txt/cord-261718-zqoggwnk.txt cache: ./cache/cord-261718-zqoggwnk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-261718-zqoggwnk.txt' === file2bib.sh === id: cord-103888-ggm29vrz author: Nova, Nicole title: Susceptible host availability modulates climate effects on dengue dynamics date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-103888-ggm29vrz.txt cache: ./cache/cord-103888-ggm29vrz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103888-ggm29vrz.txt' === file2bib.sh === id: cord-253447-4w6caxwu author: Zeng, Xin title: Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-253447-4w6caxwu.txt cache: ./cache/cord-253447-4w6caxwu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-253447-4w6caxwu.txt' === file2bib.sh === id: cord-104122-klvx927g author: Tayfuroglu, Omer title: An Accurate Free Energy Method for Solvation of Organic Compounds and Binding to Proteins date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-104122-klvx927g.txt cache: ./cache/cord-104122-klvx927g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-104122-klvx927g.txt' === file2bib.sh === id: cord-259340-1ir19s25 author: Das, Rohit Pritam title: Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-259340-1ir19s25.txt cache: ./cache/cord-259340-1ir19s25.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-259340-1ir19s25.txt' === file2bib.sh === id: cord-254636-3lr008th author: Shishir, Tushar Ahmed title: In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-254636-3lr008th.txt cache: ./cache/cord-254636-3lr008th.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254636-3lr008th.txt' === file2bib.sh === id: cord-259246-azt5sr9w author: Peng, Qi title: Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-259246-azt5sr9w.txt cache: ./cache/cord-259246-azt5sr9w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259246-azt5sr9w.txt' === file2bib.sh === id: cord-259620-qigfstxt author: Yang, Chen title: Kidney injury molecule-1 is a potential receptor for SARS-CoV-2 date: 2020-10-10 pages: extension: .txt txt: ./txt/cord-259620-qigfstxt.txt cache: ./cache/cord-259620-qigfstxt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259620-qigfstxt.txt' === file2bib.sh === id: cord-104146-pabh3ajb author: de Lussanet de la Sablonière, Marc H. E. title: Robust, general purpose, digital power line hum filter which is free of deformations and which can be applied to large transients date: 2019-11-04 pages: extension: .txt txt: ./txt/cord-104146-pabh3ajb.txt cache: ./cache/cord-104146-pabh3ajb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 104 resourceName b'cord-104146-pabh3ajb.txt' === file2bib.sh === id: cord-259261-fmuozy3w author: Bickler, Stephen W. title: AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-259261-fmuozy3w.txt cache: ./cache/cord-259261-fmuozy3w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-259261-fmuozy3w.txt' === file2bib.sh === id: cord-104055-47ren7ie author: Lutkenhoff, Evan S. title: EEG power spectra and subcortical pathology in chronic disorders of consciousness date: 2020-09-01 pages: extension: .txt txt: ./txt/cord-104055-47ren7ie.txt cache: ./cache/cord-104055-47ren7ie.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104055-47ren7ie.txt' === file2bib.sh === id: cord-104138-qagyaegp author: Magee, Michelle title: Effects of face masks on acoustic analysis and speech perception: Implications for peri-pandemic protocols date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-104138-qagyaegp.txt cache: ./cache/cord-104138-qagyaegp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104138-qagyaegp.txt' === file2bib.sh === id: cord-103940-a2cqw8kg author: Shi, Yuejun title: Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins date: 2020-06-09 pages: extension: .txt txt: ./txt/cord-103940-a2cqw8kg.txt cache: ./cache/cord-103940-a2cqw8kg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103940-a2cqw8kg.txt' === file2bib.sh === id: cord-104162-fe51v2pt author: Zhang, Chiyu title: Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-104162-fe51v2pt.txt cache: ./cache/cord-104162-fe51v2pt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 34 resourceName b'cord-104162-fe51v2pt.txt' === file2bib.sh === id: cord-254855-gmy9zyad author: He, Sijia title: PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-254855-gmy9zyad.txt cache: ./cache/cord-254855-gmy9zyad.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254855-gmy9zyad.txt' === file2bib.sh === id: cord-104073-vsa5y7ip author: Warner, Emily F. title: Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-104073-vsa5y7ip.txt cache: ./cache/cord-104073-vsa5y7ip.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 68 resourceName b'cord-104073-vsa5y7ip.txt' === file2bib.sh === id: cord-104161-jvbgouv8 author: Pfrieger, Frank W. title: Insight into the workforce advancing fields of science and technology date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-104161-jvbgouv8.txt cache: ./cache/cord-104161-jvbgouv8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-104161-jvbgouv8.txt' === file2bib.sh === id: cord-104030-eb29t38n author: Morales-Nebreda, Luisa title: Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-104030-eb29t38n.txt cache: ./cache/cord-104030-eb29t38n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-104030-eb29t38n.txt' === file2bib.sh === id: cord-103946-c5i8btp7 author: Li, Maohua title: Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-103946-c5i8btp7.txt cache: ./cache/cord-103946-c5i8btp7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103946-c5i8btp7.txt' === file2bib.sh === id: cord-103895-dt0ers70 author: Zeng, Xiangrui title: Comparative Pathway Integrator: a framework of meta-analytic integration of multiple transcriptomic studies for consensual and differential pathway analysis date: 2018-10-16 pages: extension: .txt txt: ./txt/cord-103895-dt0ers70.txt cache: ./cache/cord-103895-dt0ers70.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103895-dt0ers70.txt' === file2bib.sh === id: cord-262145-i29e3fge author: Huang, Kuan-Ying A. title: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-262145-i29e3fge.txt cache: ./cache/cord-262145-i29e3fge.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262145-i29e3fge.txt' === file2bib.sh === id: cord-104092-yau3r79c author: Tamming, Renee J. title: Atrx deletion in neurons leads to sexually-dimorphic dysregulation of miR-137 and spatial learning and memory deficits date: 2019-04-13 pages: extension: .txt txt: ./txt/cord-104092-yau3r79c.txt cache: ./cache/cord-104092-yau3r79c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-104092-yau3r79c.txt' === file2bib.sh === id: cord-261961-u4d0vvmq author: St-Germain, Jonathan R. title: A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-261961-u4d0vvmq.txt cache: ./cache/cord-261961-u4d0vvmq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-261961-u4d0vvmq.txt' === file2bib.sh === id: cord-260352-rhd0qqyn author: Bhattacharyya, Sumit title: Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity date: 2020-06-25 pages: extension: .txt txt: ./txt/cord-260352-rhd0qqyn.txt cache: ./cache/cord-260352-rhd0qqyn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-260352-rhd0qqyn.txt' === file2bib.sh === id: cord-103964-k6jnv87v author: Friedl, Jana title: More than just a ticket canceller: The mitochondrial processing peptidase matures complex precursor proteins at internal cleavage sites date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-103964-k6jnv87v.txt cache: ./cache/cord-103964-k6jnv87v.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103964-k6jnv87v.txt' === file2bib.sh === id: cord-104142-0nfprn2a author: Azmi, Maryam A. title: A laboratory module that explores RNA interference and codon optimization through fluorescence microscopy using Caenorhabditis elegans date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-104142-0nfprn2a.txt cache: ./cache/cord-104142-0nfprn2a.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 24 resourceName b'cord-104142-0nfprn2a.txt' === file2bib.sh === id: cord-255755-5jccb3nh author: Saha, Sovan title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-255755-5jccb3nh.txt cache: ./cache/cord-255755-5jccb3nh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255755-5jccb3nh.txt' === file2bib.sh === id: cord-261688-njlxrxv6 author: Yang, Ziwei title: Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2 date: 2020-08-12 pages: extension: .txt txt: ./txt/cord-261688-njlxrxv6.txt cache: ./cache/cord-261688-njlxrxv6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261688-njlxrxv6.txt' === file2bib.sh === id: cord-252910-7qvnj6c8 author: Li, Xin title: The discovery of a recombinant SARS2-like CoV strain provides insights into SARS and COVID-19 pandemics date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-252910-7qvnj6c8.txt cache: ./cache/cord-252910-7qvnj6c8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-252910-7qvnj6c8.txt' === file2bib.sh === id: cord-104081-a3fx8tyd author: Tang, Tiffany title: Proteolytic activation of the SARS-CoV-2 spike S1/S2 site: a re-evaluation of furin cleavage date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-104081-a3fx8tyd.txt cache: ./cache/cord-104081-a3fx8tyd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104081-a3fx8tyd.txt' === file2bib.sh === id: cord-103990-qvuv289g author: Amster, Guy title: Changes in life history and population size can explain relative neutral diversity levels on X and autosomes in extant human populations date: 2019-09-09 pages: extension: .txt txt: ./txt/cord-103990-qvuv289g.txt cache: ./cache/cord-103990-qvuv289g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103990-qvuv289g.txt' === file2bib.sh === id: cord-103864-4kec8re4 author: Miao, Zhen title: Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets date: 2020-06-04 pages: extension: .txt txt: ./txt/cord-103864-4kec8re4.txt cache: ./cache/cord-103864-4kec8re4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103864-4kec8re4.txt' === file2bib.sh === id: cord-262958-tmp6yxlv author: Pinto, Dora title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-262958-tmp6yxlv.txt cache: ./cache/cord-262958-tmp6yxlv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262958-tmp6yxlv.txt' === file2bib.sh === id: cord-255371-o9oxchq6 author: Nguyen, Thanh Thi title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-255371-o9oxchq6.txt cache: ./cache/cord-255371-o9oxchq6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-255371-o9oxchq6.txt' === file2bib.sh === id: cord-104001-5clslvqb author: Wang, Xiaoqi title: selfRL: Two-Level Self-Supervised Transformer Representation Learning for Link Prediction of Heterogeneous Biomedical Networks date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-104001-5clslvqb.txt cache: ./cache/cord-104001-5clslvqb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104001-5clslvqb.txt' === file2bib.sh === id: cord-104133-d01joq23 author: Arthur, Ronan F. title: Adaptive social contact rates induce complex dynamics during epidemics date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-104133-d01joq23.txt cache: ./cache/cord-104133-d01joq23.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 98 resourceName b'cord-104133-d01joq23.txt' === file2bib.sh === id: cord-260054-iihgc5nr author: Cavallo, Luigi title: D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-260054-iihgc5nr.txt cache: ./cache/cord-260054-iihgc5nr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-260054-iihgc5nr.txt' === file2bib.sh === id: cord-260508-z11exbyu author: Wang, Hongru title: Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-260508-z11exbyu.txt cache: ./cache/cord-260508-z11exbyu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260508-z11exbyu.txt' === file2bib.sh === id: cord-253987-83h861lp author: Tada, Takuya title: A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-253987-83h861lp.txt cache: ./cache/cord-253987-83h861lp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 26 resourceName b'cord-253987-83h861lp.txt' === file2bib.sh === id: cord-104037-39kk37fb author: Ma, Jiahao title: Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19 date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-104037-39kk37fb.txt cache: ./cache/cord-104037-39kk37fb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104037-39kk37fb.txt' === file2bib.sh === id: cord-104025-ysxc7rpl author: Cheek, Martin title: Deinbollia onanae (Sapindaceae), a new, Endangered, montane tree species from the Cameroon Highlands date: 2020-10-26 pages: extension: .txt txt: ./txt/cord-104025-ysxc7rpl.txt cache: ./cache/cord-104025-ysxc7rpl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-104025-ysxc7rpl.txt' === file2bib.sh === id: cord-255895-6at9gelt author: Han, Namshik title: Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-255895-6at9gelt.txt cache: ./cache/cord-255895-6at9gelt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255895-6at9gelt.txt' === file2bib.sh === id: cord-104169-2sbc1guz author: Satish, Swarup title: The impact of preprint servers in the formation of novel ideas date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-104169-2sbc1guz.txt cache: ./cache/cord-104169-2sbc1guz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104169-2sbc1guz.txt' === file2bib.sh === id: cord-254772-1xzkfl8g author: Pandolfi, Laura title: Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis date: 2020-11-09 pages: extension: .txt txt: ./txt/cord-254772-1xzkfl8g.txt cache: ./cache/cord-254772-1xzkfl8g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-254772-1xzkfl8g.txt' === file2bib.sh === id: cord-103853-ar09nzmw author: Wayment-Steele, Hannah K. title: RNA secondary structure packages ranked and improved by high-throughput experiments date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-103853-ar09nzmw.txt cache: ./cache/cord-103853-ar09nzmw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103853-ar09nzmw.txt' === file2bib.sh === id: cord-104036-790vk1cf author: Liekkinen, Juho title: Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level date: 2020-07-08 pages: extension: .txt txt: ./txt/cord-104036-790vk1cf.txt cache: ./cache/cord-104036-790vk1cf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 92 resourceName b'cord-104036-790vk1cf.txt' === file2bib.sh === id: cord-104128-0gyk9cwx author: Morand, Serge title: The accelerated infectious disease risk in the Anthropocene: more outbreaks and wider global spread date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-104128-0gyk9cwx.txt cache: ./cache/cord-104128-0gyk9cwx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104128-0gyk9cwx.txt' === file2bib.sh === id: cord-104008-luqvw0y8 author: Levinson, Julia title: Investigating the effectiveness of school health services delivered by a health provider: a systematic review of systematic reviews date: 2019-02-07 pages: extension: .txt txt: ./txt/cord-104008-luqvw0y8.txt cache: ./cache/cord-104008-luqvw0y8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104008-luqvw0y8.txt' === file2bib.sh === id: cord-103788-sxw4l9tt author: Talbot, Steven R. title: One score to rule them all: severity assessment in laboratory mice date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-103788-sxw4l9tt.txt cache: ./cache/cord-103788-sxw4l9tt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103788-sxw4l9tt.txt' === file2bib.sh === id: cord-252097-4kslllaq author: Kaur, S. title: Local computational methods to improve the interpretability and analysis of cryo-EM maps date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-252097-4kslllaq.txt cache: ./cache/cord-252097-4kslllaq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-252097-4kslllaq.txt' === file2bib.sh === id: cord-260315-uau554jj author: Ramirez, Santseharay title: Efficient culture of SARS-CoV-2 in human hepatoma cells enhances viability of the virus in human lung cancer cell lines permitting the screening of antiviral compounds date: 2020-10-04 pages: extension: .txt txt: ./txt/cord-260315-uau554jj.txt cache: ./cache/cord-260315-uau554jj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-260315-uau554jj.txt' === file2bib.sh === id: cord-255440-ls1l2mlg author: Tindle, Courtney title: Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19 date: 2020-10-18 pages: extension: .txt txt: ./txt/cord-255440-ls1l2mlg.txt cache: ./cache/cord-255440-ls1l2mlg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255440-ls1l2mlg.txt' === file2bib.sh === id: cord-103892-v6gkubd4 author: Mäkinen, Janne J. title: The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-103892-v6gkubd4.txt cache: ./cache/cord-103892-v6gkubd4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103892-v6gkubd4.txt' === file2bib.sh === id: cord-255515-7se14455 author: Graudenzi, Alex title: Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-255515-7se14455.txt cache: ./cache/cord-255515-7se14455.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-255515-7se14455.txt' === file2bib.sh === id: cord-252597-ea78sjcs author: Ramazzotti, Daniele title: VERSO: a comprehensive framework for the inference of robust phylogenies and the quantification of intra-host genomic diversity of viral samples date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-252597-ea78sjcs.txt cache: ./cache/cord-252597-ea78sjcs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252597-ea78sjcs.txt' === file2bib.sh === id: cord-103914-ppgx7mci author: Maughan, Elizabeth F. title: Cell-intrinsic differences between human airway epithelial cells from children and adults date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-103914-ppgx7mci.txt cache: ./cache/cord-103914-ppgx7mci.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103914-ppgx7mci.txt' === file2bib.sh === id: cord-104140-o46kvd0b author: McPherson, Malinda J. title: Harmonicity aids hearing in noise date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-104140-o46kvd0b.txt cache: ./cache/cord-104140-o46kvd0b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 52 resourceName b'cord-104140-o46kvd0b.txt' === file2bib.sh === id: cord-258630-mvz2l3yj author: Liu, Tiantian title: A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-258630-mvz2l3yj.txt cache: ./cache/cord-258630-mvz2l3yj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 82 resourceName b'cord-258630-mvz2l3yj.txt' === file2bib.sh === id: cord-103925-i73ymrov author: Hill, Chris H. title: Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-103925-i73ymrov.txt cache: ./cache/cord-103925-i73ymrov.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-103925-i73ymrov.txt' === file2bib.sh === id: cord-103915-rzy7mejb author: Duricki, Denise A. title: Corticospinal neuroplasticity and sensorimotor recovery in rats treated by infusion of neurotrophin-3 into disabled forelimb muscles started 24 h after stroke date: 2018-07-11 pages: extension: .txt txt: ./txt/cord-103915-rzy7mejb.txt cache: ./cache/cord-103915-rzy7mejb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103915-rzy7mejb.txt' === file2bib.sh === id: cord-104157-rivaoo73 author: Noreika, Valdas title: Alertness fluctuations during task performance modulate cortical evoked responses to transcranial magnetic stimulation date: 2019-06-28 pages: extension: .txt txt: ./txt/cord-104157-rivaoo73.txt cache: ./cache/cord-104157-rivaoo73.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104157-rivaoo73.txt' === file2bib.sh === id: cord-259084-lwh3rww4 author: Anderson, Cole title: Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2 date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-259084-lwh3rww4.txt cache: ./cache/cord-259084-lwh3rww4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-259084-lwh3rww4.txt' === file2bib.sh === id: cord-103757-fed21fhu author: McPherson, Malinda J. title: Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory date: 2020-10-15 pages: extension: .txt txt: ./txt/cord-103757-fed21fhu.txt cache: ./cache/cord-103757-fed21fhu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 15 resourceName b'cord-103757-fed21fhu.txt' === file2bib.sh === id: cord-255997-oer5lxxr author: Onodi, Fanny title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-255997-oer5lxxr.txt cache: ./cache/cord-255997-oer5lxxr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255997-oer5lxxr.txt' === file2bib.sh === id: cord-104031-vodwptdo author: Altshuler, Anna title: Capturing limbal epithelial stem cell population dynamics, signature, and their niche date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-104031-vodwptdo.txt cache: ./cache/cord-104031-vodwptdo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-104031-vodwptdo.txt' === file2bib.sh === id: cord-262573-wdgbno9p author: Begum, Feroza title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India date: 2020-05-03 pages: extension: .txt txt: ./txt/cord-262573-wdgbno9p.txt cache: ./cache/cord-262573-wdgbno9p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-262573-wdgbno9p.txt' === file2bib.sh === id: cord-267223-pf799wbw author: de Lamballerie, Claire Nicolas title: Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection in a human airway epithelial model date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-267223-pf799wbw.txt cache: ./cache/cord-267223-pf799wbw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-267223-pf799wbw.txt' === file2bib.sh === id: cord-267536-rvhwl4ea author: Miyashita, L title: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-267536-rvhwl4ea.txt cache: ./cache/cord-267536-rvhwl4ea.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267536-rvhwl4ea.txt' === file2bib.sh === id: cord-263780-8jejswuk author: Wang, Nan title: Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-263780-8jejswuk.txt cache: ./cache/cord-263780-8jejswuk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-263780-8jejswuk.txt' === file2bib.sh === id: cord-264012-q2quyijg author: Lim, Su Bin title: ACE2-expressing endothelial cells in aging mouse brain date: 2020-07-11 pages: extension: .txt txt: ./txt/cord-264012-q2quyijg.txt cache: ./cache/cord-264012-q2quyijg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264012-q2quyijg.txt' === file2bib.sh === id: cord-269285-2r40mico author: Resnick, Samuel J. title: A simplified cell-based assay to identify coronavirus 3CL protease inhibitors date: 2020-08-29 pages: extension: .txt txt: ./txt/cord-269285-2r40mico.txt cache: ./cache/cord-269285-2r40mico.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-269285-2r40mico.txt' === file2bib.sh === id: cord-263594-jd9ako6c author: Kang, Sisi title: A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-263594-jd9ako6c.txt cache: ./cache/cord-263594-jd9ako6c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263594-jd9ako6c.txt' === file2bib.sh === id: cord-261855-qpbgq5d8 author: Walker, Susanne N. title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-261855-qpbgq5d8.txt cache: ./cache/cord-261855-qpbgq5d8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261855-qpbgq5d8.txt' === file2bib.sh === id: cord-268034-7id7sfsu author: Auerswald, Heidi title: Assessment of Inactivation Procedures for SARS-CoV-2 date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-268034-7id7sfsu.txt cache: ./cache/cord-268034-7id7sfsu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268034-7id7sfsu.txt' === file2bib.sh === id: cord-270698-9w3ap3gz author: Guo, Hua title: Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-270698-9w3ap3gz.txt cache: ./cache/cord-270698-9w3ap3gz.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270698-9w3ap3gz.txt' === file2bib.sh === id: cord-262485-sx2q5ol4 author: Davda, Jayeshkumar Narsibhai title: An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-262485-sx2q5ol4.txt cache: ./cache/cord-262485-sx2q5ol4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262485-sx2q5ol4.txt' === file2bib.sh === id: cord-265453-z6aux01t author: Bierig, Tobias title: Design, expression, purification and characterization of a YFP-tagged 2019-nCoV spike receptor-binding domain construct date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-265453-z6aux01t.txt cache: ./cache/cord-265453-z6aux01t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265453-z6aux01t.txt' === file2bib.sh === id: cord-261662-d0tg9i90 author: Andres, Cristina title: Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-261662-d0tg9i90.txt cache: ./cache/cord-261662-d0tg9i90.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-261662-d0tg9i90.txt' === file2bib.sh === id: cord-270919-0hldozml author: Cortey, Martí title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins date: 2020-05-17 pages: extension: .txt txt: ./txt/cord-270919-0hldozml.txt cache: ./cache/cord-270919-0hldozml.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270919-0hldozml.txt' === file2bib.sh === id: cord-263970-9w6ciglv author: Marquez-Miranda, Valeria title: Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-263970-9w6ciglv.txt cache: ./cache/cord-263970-9w6ciglv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263970-9w6ciglv.txt' === file2bib.sh === id: cord-267845-18hb5ndr author: Resende, Paola Cristina title: SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-267845-18hb5ndr.txt cache: ./cache/cord-267845-18hb5ndr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267845-18hb5ndr.txt' === file2bib.sh === id: cord-270049-54t3w94z author: Campione, Elena title: Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidences date: 2020-08-17 pages: extension: .txt txt: ./txt/cord-270049-54t3w94z.txt cache: ./cache/cord-270049-54t3w94z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-270049-54t3w94z.txt' === file2bib.sh === id: cord-266869-fs8dn7ir author: Kim, So Young title: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-266869-fs8dn7ir.txt cache: ./cache/cord-266869-fs8dn7ir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266869-fs8dn7ir.txt' === file2bib.sh === id: cord-268795-tjmx6msm author: Sardar, Rahila title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis date: 2020-03-21 pages: extension: .txt txt: ./txt/cord-268795-tjmx6msm.txt cache: ./cache/cord-268795-tjmx6msm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268795-tjmx6msm.txt' === file2bib.sh === id: cord-270257-5f95gve3 author: Jeon, Sangeun title: Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs date: 2020-03-28 pages: extension: .txt txt: ./txt/cord-270257-5f95gve3.txt cache: ./cache/cord-270257-5f95gve3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270257-5f95gve3.txt' === file2bib.sh === id: cord-267831-uu883ofc author: Kang, Yuan-Lin title: Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2 date: 2020-06-15 pages: extension: .txt txt: ./txt/cord-267831-uu883ofc.txt cache: ./cache/cord-267831-uu883ofc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267831-uu883ofc.txt' === file2bib.sh === id: cord-263825-g8p2lsr0 author: Maldonado, Lucas L. title: Molecular features similarities between SARS-CoV-2, SARS, MERS and key human genes could favour the viral infections and trigger collateral effects date: 2020-06-25 pages: extension: .txt txt: ./txt/cord-263825-g8p2lsr0.txt cache: ./cache/cord-263825-g8p2lsr0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263825-g8p2lsr0.txt' === file2bib.sh === id: cord-268339-jxm69ndw author: Karamitros, Timokratis title: SARS-CoV-2 exhibits intra-host genomic plasticity and low-frequency polymorphic quasispecies date: 2020-03-28 pages: extension: .txt txt: ./txt/cord-268339-jxm69ndw.txt cache: ./cache/cord-268339-jxm69ndw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268339-jxm69ndw.txt' === file2bib.sh === id: cord-279474-c5y2lygj author: Bozzo, Caterina Prelli title: IFITM proteins promote SARS-CoV-2 infection of human lung cells date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-279474-c5y2lygj.txt cache: ./cache/cord-279474-c5y2lygj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-279474-c5y2lygj.txt' === file2bib.sh === id: cord-271971-rstmd0va author: Matsumura, Yasufumi title: Comparison of 12 molecular detection assays for SARS-CoV-2 date: 2020-06-25 pages: extension: .txt txt: ./txt/cord-271971-rstmd0va.txt cache: ./cache/cord-271971-rstmd0va.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271971-rstmd0va.txt' === file2bib.sh === id: cord-270329-t60t639i author: Schloer, Sebastian title: Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro date: 2020-10-16 pages: extension: .txt txt: ./txt/cord-270329-t60t639i.txt cache: ./cache/cord-270329-t60t639i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270329-t60t639i.txt' === file2bib.sh === id: cord-263008-w6twrjzr author: Yin, Rui title: Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide date: 2020-07-15 pages: extension: .txt txt: ./txt/cord-263008-w6twrjzr.txt cache: ./cache/cord-263008-w6twrjzr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-263008-w6twrjzr.txt' === file2bib.sh === id: cord-265418-yqe9vdj1 author: Kumar, Nilesh title: Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-265418-yqe9vdj1.txt cache: ./cache/cord-265418-yqe9vdj1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-265418-yqe9vdj1.txt' === file2bib.sh === id: cord-264031-0y7xbgun author: Wierbowski, Shayne D. title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-264031-0y7xbgun.txt cache: ./cache/cord-264031-0y7xbgun.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264031-0y7xbgun.txt' === file2bib.sh === id: cord-264204-4ablrwuo author: Guintivano, Jerry title: Psychiatric Genomics Research During the COVID-19 Pandemic: A Survey of Psychiatric Genomics Consortium Researchers date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-264204-4ablrwuo.txt cache: ./cache/cord-264204-4ablrwuo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-264204-4ablrwuo.txt' === file2bib.sh === id: cord-265277-ymvrserl author: Crooke, Stephen N. title: Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome date: 2020-05-14 pages: extension: .txt txt: ./txt/cord-265277-ymvrserl.txt cache: ./cache/cord-265277-ymvrserl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-265277-ymvrserl.txt' === file2bib.sh === id: cord-268894-amfv3z2y author: Nguyen-Contant, Phuong title: S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-268894-amfv3z2y.txt cache: ./cache/cord-268894-amfv3z2y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-268894-amfv3z2y.txt' === file2bib.sh === id: cord-271978-j5enftje author: Zoltán, Köntös title: In Vitro Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-271978-j5enftje.txt cache: ./cache/cord-271978-j5enftje.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-271978-j5enftje.txt' === file2bib.sh === id: cord-273416-332stbjl author: Liu, Tianyuan title: Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-273416-332stbjl.txt cache: ./cache/cord-273416-332stbjl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273416-332stbjl.txt' === file2bib.sh === id: cord-273882-tqdcb3oo author: Pratibha, title: Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-273882-tqdcb3oo.txt cache: ./cache/cord-273882-tqdcb3oo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273882-tqdcb3oo.txt' === file2bib.sh === id: cord-272626-bw9lbzvt author: Pizzorno, Andrés title: Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia date: 2020-04-02 pages: extension: .txt txt: ./txt/cord-272626-bw9lbzvt.txt cache: ./cache/cord-272626-bw9lbzvt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272626-bw9lbzvt.txt' === file2bib.sh === id: cord-278869-7zr1118b author: Ravichandran, Supriya title: Antibody repertoire induced by SARS-CoV-2 spike protein immunogens date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-278869-7zr1118b.txt cache: ./cache/cord-278869-7zr1118b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-278869-7zr1118b.txt' === file2bib.sh === id: cord-273645-czh3zfb3 author: Lu, Shuaiyao title: Comparison of SARS-CoV-2 infections among 3 species of non-human primates date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-273645-czh3zfb3.txt cache: ./cache/cord-273645-czh3zfb3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273645-czh3zfb3.txt' === file2bib.sh === id: cord-275173-ely3aen3 author: Pickering, Brad S. title: Susceptibility of domestic swine to experimental infection with SARS-CoV-2 date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-275173-ely3aen3.txt cache: ./cache/cord-275173-ely3aen3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275173-ely3aen3.txt' === file2bib.sh === id: cord-266444-rw94yls8 author: Dominguez Andres, Ana title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-266444-rw94yls8.txt cache: ./cache/cord-266444-rw94yls8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-266444-rw94yls8.txt' === file2bib.sh === id: cord-264296-0x90yubt author: Sawmya, Shashata title: Analyzing hCov genome sequences: Applying Machine Intelligence and beyond date: 2020-06-03 pages: extension: .txt txt: ./txt/cord-264296-0x90yubt.txt cache: ./cache/cord-264296-0x90yubt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264296-0x90yubt.txt' === file2bib.sh === id: cord-271693-7tg21up3 author: Zheng, Fan title: Identifying persistent structures in multiscale ‘omics data date: 2020-10-03 pages: extension: .txt txt: ./txt/cord-271693-7tg21up3.txt cache: ./cache/cord-271693-7tg21up3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-271693-7tg21up3.txt' === file2bib.sh === id: cord-263090-29n9tsk9 author: Roy, Susmita title: Dynamical asymmetry exposes 2019-nCoV prefusion spike date: 2020-04-21 pages: extension: .txt txt: ./txt/cord-263090-29n9tsk9.txt cache: ./cache/cord-263090-29n9tsk9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-263090-29n9tsk9.txt' === file2bib.sh === id: cord-280392-ij5gtesw author: Gultom, Mitra title: Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2 date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-280392-ij5gtesw.txt cache: ./cache/cord-280392-ij5gtesw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280392-ij5gtesw.txt' === file2bib.sh === id: cord-272513-umuiovrd author: Bindayna, Khalid Mubarak title: Variant analysis of SARS-CoV-2 genomes in the Middle East date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-272513-umuiovrd.txt cache: ./cache/cord-272513-umuiovrd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272513-umuiovrd.txt' === file2bib.sh === id: cord-271849-wxmr8eki author: Meysman, Pieter title: Tracking SARS-CoV-2 T cells with epitope-T-cell receptor recognition models date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-271849-wxmr8eki.txt cache: ./cache/cord-271849-wxmr8eki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-271849-wxmr8eki.txt' === file2bib.sh === id: cord-273083-xrydkiu4 author: Pahmeier, Felix title: A versatile reporter system to monitor virus infected cells and its application to dengue virus and SARS-CoV-2 date: 2020-09-01 pages: extension: .txt txt: ./txt/cord-273083-xrydkiu4.txt cache: ./cache/cord-273083-xrydkiu4.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-273083-xrydkiu4.txt' === file2bib.sh === id: cord-273891-7w334xgt author: Kirchdoerfer, Robert N. title: Receptor binding and proteolysis do not induce large conformational changes in the SARS-CoV spike date: 2018-03-31 pages: extension: .txt txt: ./txt/cord-273891-7w334xgt.txt cache: ./cache/cord-273891-7w334xgt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-273891-7w334xgt.txt' === file2bib.sh === id: cord-274409-4ugdxbmy author: Laskar, Rezwanuzzaman title: Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-274409-4ugdxbmy.txt cache: ./cache/cord-274409-4ugdxbmy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274409-4ugdxbmy.txt' === file2bib.sh === id: cord-280994-w8dtfjel author: Peng, Qi title: Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from COVID-19 virus date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-280994-w8dtfjel.txt cache: ./cache/cord-280994-w8dtfjel.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-280994-w8dtfjel.txt' === file2bib.sh === id: cord-277253-vy0mvzeb author: Liu, Hongbo title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-277253-vy0mvzeb.txt cache: ./cache/cord-277253-vy0mvzeb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-277253-vy0mvzeb.txt' === file2bib.sh === id: cord-272986-ebgusf3o author: Cao, Yipeng title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel date: 2020-05-17 pages: extension: .txt txt: ./txt/cord-272986-ebgusf3o.txt cache: ./cache/cord-272986-ebgusf3o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272986-ebgusf3o.txt' === file2bib.sh === id: cord-276017-2375ipkk author: Chen, Dongsheng title: Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife date: 2020-06-14 pages: extension: .txt txt: ./txt/cord-276017-2375ipkk.txt cache: ./cache/cord-276017-2375ipkk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-276017-2375ipkk.txt' === file2bib.sh === id: cord-275252-4e3cn50u author: Rad SM, Ali Hosseini title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date: 2020-05-16 pages: extension: .txt txt: ./txt/cord-275252-4e3cn50u.txt cache: ./cache/cord-275252-4e3cn50u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-275252-4e3cn50u.txt' === file2bib.sh === id: cord-274114-fglyfz8p author: Minervina, Anastasia A. title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-274114-fglyfz8p.txt cache: ./cache/cord-274114-fglyfz8p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-274114-fglyfz8p.txt' === file2bib.sh === id: cord-267115-6jqdi417 author: Giobbe, Giovanni Giuseppe title: SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-267115-6jqdi417.txt cache: ./cache/cord-267115-6jqdi417.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267115-6jqdi417.txt' === file2bib.sh === id: cord-267613-hsc2x36j author: Dittmar, Mark title: Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2 date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-267613-hsc2x36j.txt cache: ./cache/cord-267613-hsc2x36j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-267613-hsc2x36j.txt' === file2bib.sh === id: cord-275690-83nrzfon author: Stanifer, Megan L. title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-275690-83nrzfon.txt cache: ./cache/cord-275690-83nrzfon.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-275690-83nrzfon.txt' === file2bib.sh === id: cord-284354-aoti88v7 author: Lupala, Cecylia S. title: Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 date: 2020-05-04 pages: extension: .txt txt: ./txt/cord-284354-aoti88v7.txt cache: ./cache/cord-284354-aoti88v7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-284354-aoti88v7.txt' === file2bib.sh === id: cord-281684-m3m4mhye author: Fagre, Anna C. title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-281684-m3m4mhye.txt cache: ./cache/cord-281684-m3m4mhye.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-281684-m3m4mhye.txt' === file2bib.sh === id: cord-267482-afqfymbq author: Ryu, Seungjin title: Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model date: 2020-09-12 pages: extension: .txt txt: ./txt/cord-267482-afqfymbq.txt cache: ./cache/cord-267482-afqfymbq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267482-afqfymbq.txt' === file2bib.sh === id: cord-280198-bhjw6xc5 author: Olaleye, Omonike A. title: Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-280198-bhjw6xc5.txt cache: ./cache/cord-280198-bhjw6xc5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-280198-bhjw6xc5.txt' === file2bib.sh === id: cord-270550-if748w2n author: Bailey, Adam L. title: SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-270550-if748w2n.txt cache: ./cache/cord-270550-if748w2n.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270550-if748w2n.txt' === file2bib.sh === id: cord-273613-cpiveo7j author: Cao, Xia title: Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach date: 2020-09-29 pages: extension: .txt txt: ./txt/cord-273613-cpiveo7j.txt cache: ./cache/cord-273613-cpiveo7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-273613-cpiveo7j.txt' === file2bib.sh === id: cord-271970-i35pic5o author: Boris, Bonaventure title: A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date: 2020-10-28 pages: extension: .txt txt: ./txt/cord-271970-i35pic5o.txt cache: ./cache/cord-271970-i35pic5o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-271970-i35pic5o.txt' === file2bib.sh === id: cord-282795-kje7rn57 author: Zheng, Yue title: Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-282795-kje7rn57.txt cache: ./cache/cord-282795-kje7rn57.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-282795-kje7rn57.txt' === file2bib.sh === id: cord-272869-381qupdn author: Mirvakili, Seyed M title: Reverse Pneumatic Artificial Muscles for Application in Low-Cost Artificial Respirators date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-272869-381qupdn.txt cache: ./cache/cord-272869-381qupdn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272869-381qupdn.txt' === file2bib.sh === id: cord-281699-pxof67pl author: Eskier, Doğa title: Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load date: 2020-08-13 pages: extension: .txt txt: ./txt/cord-281699-pxof67pl.txt cache: ./cache/cord-281699-pxof67pl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281699-pxof67pl.txt' === file2bib.sh === id: cord-268224-5tbb8df1 author: Di Gioacchino, Andrea title: The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-268224-5tbb8df1.txt cache: ./cache/cord-268224-5tbb8df1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-268224-5tbb8df1.txt' === file2bib.sh === id: cord-264919-0jlg2gkc author: Hopp, Marie-Thérèse title: Unravelling the debate on heme effects in COVID-19 infections date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-264919-0jlg2gkc.txt cache: ./cache/cord-264919-0jlg2gkc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-264919-0jlg2gkc.txt' === file2bib.sh === id: cord-284102-rovyvv45 author: Wagner, Teresa R. title: NeutrobodyPlex - Nanobodies to monitor a SARS-CoV-2 neutralizing immune response date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-284102-rovyvv45.txt cache: ./cache/cord-284102-rovyvv45.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284102-rovyvv45.txt' === file2bib.sh === id: cord-279629-t1xjy12y author: Nazneen Akhand, Mst Rubaiat title: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-279629-t1xjy12y.txt cache: ./cache/cord-279629-t1xjy12y.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279629-t1xjy12y.txt' === file2bib.sh === id: cord-274528-mr81o9cu author: Li, Fei title: Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide date: 2020-09-12 pages: extension: .txt txt: ./txt/cord-274528-mr81o9cu.txt cache: ./cache/cord-274528-mr81o9cu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-274528-mr81o9cu.txt' === file2bib.sh === id: cord-282604-xp71rkxc author: Nikolaev, EN title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-282604-xp71rkxc.txt cache: ./cache/cord-282604-xp71rkxc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282604-xp71rkxc.txt' === file2bib.sh === id: cord-277487-jgbjxgh1 author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-277487-jgbjxgh1.txt cache: ./cache/cord-277487-jgbjxgh1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-277487-jgbjxgh1.txt' === file2bib.sh === id: cord-280979-0vaarrji author: Gauttier, V. title: Tissue-resident memory CD8 T-cell responses elicited by a single injection of a multi-target COVID-19 vaccine date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-280979-0vaarrji.txt cache: ./cache/cord-280979-0vaarrji.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-280979-0vaarrji.txt' === file2bib.sh === id: cord-264051-ps0x2es1 author: Li, Wei title: Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-264051-ps0x2es1.txt cache: ./cache/cord-264051-ps0x2es1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264051-ps0x2es1.txt' === file2bib.sh === id: cord-283109-ka3n9pft author: Arumugam, Arunkumar title: The Potential Use of Unprocessed Sample for RT-qPCR Detection of COVID-19 without an RNA Extraction Step date: 2020-04-08 pages: extension: .txt txt: ./txt/cord-283109-ka3n9pft.txt cache: ./cache/cord-283109-ka3n9pft.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283109-ka3n9pft.txt' === file2bib.sh === id: cord-261877-4y37676n author: Xu, Cong title: Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-261877-4y37676n.txt cache: ./cache/cord-261877-4y37676n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-261877-4y37676n.txt' === file2bib.sh === id: cord-284191-05djnz4p author: Bert, Nina Le title: Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-284191-05djnz4p.txt cache: ./cache/cord-284191-05djnz4p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284191-05djnz4p.txt' === file2bib.sh === id: cord-279576-wt4crton author: Fajardo, Álvaro title: Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples date: 2020-05-13 pages: extension: .txt txt: ./txt/cord-279576-wt4crton.txt cache: ./cache/cord-279576-wt4crton.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-279576-wt4crton.txt' === file2bib.sh === id: cord-282372-nmii30mc author: Youk, Jeonghwan title: Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection date: 2020-07-10 pages: extension: .txt txt: ./txt/cord-282372-nmii30mc.txt cache: ./cache/cord-282372-nmii30mc.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282372-nmii30mc.txt' === file2bib.sh === id: cord-291012-y0ufzx93 author: Ye, Qing title: SARS-CoV-2 infection causes transient olfactory dysfunction in mice date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-291012-y0ufzx93.txt cache: ./cache/cord-291012-y0ufzx93.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291012-y0ufzx93.txt' === file2bib.sh === id: cord-280922-w6a5ec06 author: Sen, Sanjana title: Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-280922-w6a5ec06.txt cache: ./cache/cord-280922-w6a5ec06.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280922-w6a5ec06.txt' === file2bib.sh === id: cord-284068-sbon3aes author: Mok, Chee Keng title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-284068-sbon3aes.txt cache: ./cache/cord-284068-sbon3aes.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284068-sbon3aes.txt' === file2bib.sh === id: cord-285088-krim73zt author: Wang, Deguo title: One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay date: 2020-04-21 pages: extension: .txt txt: ./txt/cord-285088-krim73zt.txt cache: ./cache/cord-285088-krim73zt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-285088-krim73zt.txt' === file2bib.sh === id: cord-286001-pu1fetq7 author: Zang, Ruochen title: TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-286001-pu1fetq7.txt cache: ./cache/cord-286001-pu1fetq7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-286001-pu1fetq7.txt' === file2bib.sh === id: cord-286810-kq2gu5cc author: Klein, Joshua A. title: Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-286810-kq2gu5cc.txt cache: ./cache/cord-286810-kq2gu5cc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-286810-kq2gu5cc.txt' === file2bib.sh === id: cord-280454-etf32afd author: Moustaqil, Mehdi title: SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-280454-etf32afd.txt cache: ./cache/cord-280454-etf32afd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280454-etf32afd.txt' === file2bib.sh === id: cord-285159-gytebbua author: Eydoux, Cecilia title: A Fluorescence-based High Throughput-Screening assay for the SARS-CoV RNA synthesis complex date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-285159-gytebbua.txt cache: ./cache/cord-285159-gytebbua.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285159-gytebbua.txt' === file2bib.sh === id: cord-286466-scokdxp2 author: Tani, Hideki title: Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein date: 2020-08-23 pages: extension: .txt txt: ./txt/cord-286466-scokdxp2.txt cache: ./cache/cord-286466-scokdxp2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-286466-scokdxp2.txt' === file2bib.sh === id: cord-284627-qvz63m93 author: Banerjee, Shuvam title: Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-284627-qvz63m93.txt cache: ./cache/cord-284627-qvz63m93.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284627-qvz63m93.txt' === file2bib.sh === id: cord-291420-40xsypzt author: Nelson-Sathi, Shijulal title: Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-291420-40xsypzt.txt cache: ./cache/cord-291420-40xsypzt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291420-40xsypzt.txt' === file2bib.sh === id: cord-281717-kzd9vvci author: Digard, Paul title: Intra-genome variability in the dinucleotide composition of SARS-CoV-2 date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-281717-kzd9vvci.txt cache: ./cache/cord-281717-kzd9vvci.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281717-kzd9vvci.txt' === file2bib.sh === id: cord-290694-jmav8xi4 author: Bridgland, Victoria M. E. title: Why the COVID-19 pandemic is a traumatic stressor date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-290694-jmav8xi4.txt cache: ./cache/cord-290694-jmav8xi4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-290694-jmav8xi4.txt' === file2bib.sh === id: cord-262119-s6hc7fxs author: Ostaszewski, Marek title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-262119-s6hc7fxs.txt cache: ./cache/cord-262119-s6hc7fxs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262119-s6hc7fxs.txt' === file2bib.sh === id: cord-285592-0in22wzv author: Lemoine, Frédéric title: COVID-Align: Accurate online alignment of hCoV-19 genomes using a profile HMM date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-285592-0in22wzv.txt cache: ./cache/cord-285592-0in22wzv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-285592-0in22wzv.txt' === file2bib.sh === id: cord-291710-ixun0c8g author: Su, Haixia title: Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-291710-ixun0c8g.txt cache: ./cache/cord-291710-ixun0c8g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291710-ixun0c8g.txt' === file2bib.sh === id: cord-289367-zna8qkkv author: Wirden, Marc title: Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2 date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-289367-zna8qkkv.txt cache: ./cache/cord-289367-zna8qkkv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289367-zna8qkkv.txt' === file2bib.sh === id: cord-295560-0rpguepv author: Yan, Kexin title: Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-295560-0rpguepv.txt cache: ./cache/cord-295560-0rpguepv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-295560-0rpguepv.txt' === file2bib.sh === id: cord-284045-scd3f8vk author: Pape, Constantin title: Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-284045-scd3f8vk.txt cache: ./cache/cord-284045-scd3f8vk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-284045-scd3f8vk.txt' === file2bib.sh === id: cord-294120-8fxrqorg author: Guebre-Xabier, Mimi title: NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-294120-8fxrqorg.txt cache: ./cache/cord-294120-8fxrqorg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294120-8fxrqorg.txt' === file2bib.sh === id: cord-295545-ruxz77i8 author: Hennighausen, Lothar title: Activation of the SARS-CoV-2 receptor Ace2 by cytokines through pan JAK-STAT enhancers date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-295545-ruxz77i8.txt cache: ./cache/cord-295545-ruxz77i8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295545-ruxz77i8.txt' === file2bib.sh === id: cord-281679-xmbnpawj author: Meekins, David A. title: Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-281679-xmbnpawj.txt cache: ./cache/cord-281679-xmbnpawj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281679-xmbnpawj.txt' === file2bib.sh === id: cord-290445-vb53bih9 author: Ahmed, Shiek SSJ title: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date: 2020-04-23 pages: extension: .txt txt: ./txt/cord-290445-vb53bih9.txt cache: ./cache/cord-290445-vb53bih9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290445-vb53bih9.txt' === file2bib.sh === id: cord-287658-c2lljdi7 author: Lopez-Rincon, Alejandro title: Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-287658-c2lljdi7.txt cache: ./cache/cord-287658-c2lljdi7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287658-c2lljdi7.txt' === file2bib.sh === id: cord-293826-2p7dqacd author: Lee, Cheryl Yi-Pin title: Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-293826-2p7dqacd.txt cache: ./cache/cord-293826-2p7dqacd.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-293826-2p7dqacd.txt' === file2bib.sh === id: cord-292670-12prczym author: Urra, José Miguel title: The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-292670-12prczym.txt cache: ./cache/cord-292670-12prczym.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292670-12prczym.txt' === file2bib.sh === id: cord-293428-8hj06hzt author: Yang, Jianling title: Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-293428-8hj06hzt.txt cache: ./cache/cord-293428-8hj06hzt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293428-8hj06hzt.txt' === file2bib.sh === id: cord-297775-ug4ovsws author: Hosie, Margaret J title: Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK date: 2020-09-23 pages: extension: .txt txt: ./txt/cord-297775-ug4ovsws.txt cache: ./cache/cord-297775-ug4ovsws.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297775-ug4ovsws.txt' === file2bib.sh === id: cord-281565-v8s2ski3 author: Belmonte-Reche, Efres title: Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-281565-v8s2ski3.txt cache: ./cache/cord-281565-v8s2ski3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-281565-v8s2ski3.txt' === file2bib.sh === id: cord-281141-ouno4jpl author: Mahajan, Swapnil title: Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-281141-ouno4jpl.txt cache: ./cache/cord-281141-ouno4jpl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-281141-ouno4jpl.txt' === file2bib.sh === id: cord-287372-ya5uvoki author: Böszörményi, Kinga P. title: Comparison of SARS-CoV-2 infection in two non-human primate species: rhesus and cynomolgus macaques date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-287372-ya5uvoki.txt cache: ./cache/cord-287372-ya5uvoki.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-287372-ya5uvoki.txt' === file2bib.sh === id: cord-291677-zcbyhsf1 author: Wilamowski, M. title: Methylation of RNA Cap in SARS-CoV-2 captured by serial crystallography date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-291677-zcbyhsf1.txt cache: ./cache/cord-291677-zcbyhsf1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291677-zcbyhsf1.txt' === file2bib.sh === id: cord-297754-d4xnj551 author: Aktas, Emre title: Bioinformatic Analysis Reveals That Some Mutations May Affect On Both Spike Structure Damage and Ligand Binding Site date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-297754-d4xnj551.txt cache: ./cache/cord-297754-d4xnj551.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-297754-d4xnj551.txt' === file2bib.sh === id: cord-293640-pgrrurrc author: Tripathi, Satyendra C title: Renal carcinoma is associated with increased risk of coronavirus infections date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-293640-pgrrurrc.txt cache: ./cache/cord-293640-pgrrurrc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-293640-pgrrurrc.txt' === file2bib.sh === id: cord-297021-fzfl08qa author: Manomaipiboon, Anan title: The new silicone N99 half-piece respirator, VJR-NMU N99: A novel and effective tool to prevent COVID-19 date: 2020-07-23 pages: extension: .txt txt: ./txt/cord-297021-fzfl08qa.txt cache: ./cache/cord-297021-fzfl08qa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297021-fzfl08qa.txt' === file2bib.sh === id: cord-297787-t9neub6d author: Fu, Ziyang title: Structural basis for the inhibition of the papain-like protease of SARS-CoV-2 by small molecules date: 2020-07-18 pages: extension: .txt txt: ./txt/cord-297787-t9neub6d.txt cache: ./cache/cord-297787-t9neub6d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297787-t9neub6d.txt' === file2bib.sh === id: cord-293274-ysr1l557 author: Perisé-Barrios, Ana Judith title: Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-293274-ysr1l557.txt cache: ./cache/cord-293274-ysr1l557.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-293274-ysr1l557.txt' === file2bib.sh === id: cord-277648-9kxwkcbl author: Overholt, Kalon J. title: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-277648-9kxwkcbl.txt cache: ./cache/cord-277648-9kxwkcbl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-277648-9kxwkcbl.txt' === file2bib.sh === id: cord-287205-k64svq6n author: Pollet, Jeroen title: SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-287205-k64svq6n.txt cache: ./cache/cord-287205-k64svq6n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287205-k64svq6n.txt' === file2bib.sh === id: cord-287172-h8zoplkm author: Ghobrial, Moheb title: The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-287172-h8zoplkm.txt cache: ./cache/cord-287172-h8zoplkm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-287172-h8zoplkm.txt' === file2bib.sh === id: cord-295765-c7o2ukm6 author: Silvas, Jesus A. title: Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication date: 2020-07-20 pages: extension: .txt txt: ./txt/cord-295765-c7o2ukm6.txt cache: ./cache/cord-295765-c7o2ukm6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295765-c7o2ukm6.txt' === file2bib.sh === id: cord-296007-1gsgd22t author: Mohseni, Amir Hossein title: Inferring MHC interacting SARS-CoV-2 epitopes recognized by TCRs towards designing T cell-based vaccines date: 2020-09-12 pages: extension: .txt txt: ./txt/cord-296007-1gsgd22t.txt cache: ./cache/cord-296007-1gsgd22t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296007-1gsgd22t.txt' === file2bib.sh === id: cord-282878-8qgsq2km author: Fignani, Daniela title: SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-282878-8qgsq2km.txt cache: ./cache/cord-282878-8qgsq2km.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282878-8qgsq2km.txt' === file2bib.sh === id: cord-298321-8871aifz author: Laamarti, Meriem title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-298321-8871aifz.txt cache: ./cache/cord-298321-8871aifz.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298321-8871aifz.txt' === file2bib.sh === id: cord-299737-r34d0rx7 author: Grant, Paul R title: Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic date: 2020-04-08 pages: extension: .txt txt: ./txt/cord-299737-r34d0rx7.txt cache: ./cache/cord-299737-r34d0rx7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-299737-r34d0rx7.txt' === file2bib.sh === id: cord-291590-24psoaer author: Ogando, Natacha S. title: The enzymatic activity of the nsp14 exoribonuclease is critical for replication of Middle East respiratory syndrome-coronavirus date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-291590-24psoaer.txt cache: ./cache/cord-291590-24psoaer.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291590-24psoaer.txt' === file2bib.sh === id: cord-300783-pvn2qq0f author: Sadykov, Mukhtar title: Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction date: 2020-08-07 pages: extension: .txt txt: ./txt/cord-300783-pvn2qq0f.txt cache: ./cache/cord-300783-pvn2qq0f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300783-pvn2qq0f.txt' === file2bib.sh === id: cord-298716-pubhq564 author: Bryche, Bertrand title: Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-298716-pubhq564.txt cache: ./cache/cord-298716-pubhq564.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298716-pubhq564.txt' === file2bib.sh === id: cord-291156-zxg3dsm3 author: Bernasconi, Anna title: Empowering Virus Sequences Research through Conceptual Modeling date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-291156-zxg3dsm3.txt cache: ./cache/cord-291156-zxg3dsm3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-291156-zxg3dsm3.txt' === file2bib.sh === id: cord-296657-mymndjvd author: Higuchi, Yusuke title: High affinity modified ACE2 receptors prevent SARS-CoV-2 infection date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-296657-mymndjvd.txt cache: ./cache/cord-296657-mymndjvd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296657-mymndjvd.txt' === file2bib.sh === id: cord-296268-kb7fgfaq author: Mendonça, Luiza title: SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-296268-kb7fgfaq.txt cache: ./cache/cord-296268-kb7fgfaq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296268-kb7fgfaq.txt' === file2bib.sh === id: cord-288705-f3zqhpx1 author: Slaine, Patrick title: Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model date: 2020-10-01 pages: extension: .txt txt: ./txt/cord-288705-f3zqhpx1.txt cache: ./cache/cord-288705-f3zqhpx1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288705-f3zqhpx1.txt' === file2bib.sh === id: cord-291523-4dtk1kyh author: Nguyen, Thanh Thi title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-291523-4dtk1kyh.txt cache: ./cache/cord-291523-4dtk1kyh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-291523-4dtk1kyh.txt' === file2bib.sh === id: cord-300423-q2i328sz author: Bai, Lei title: Co-infection of influenza A virus enhances SARS-CoV-2 infectivity date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-300423-q2i328sz.txt cache: ./cache/cord-300423-q2i328sz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300423-q2i328sz.txt' === file2bib.sh === id: cord-296981-tded20ih author: Gilmore, Kerry title: In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2 date: 2020-10-05 pages: extension: .txt txt: ./txt/cord-296981-tded20ih.txt cache: ./cache/cord-296981-tded20ih.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296981-tded20ih.txt' === file2bib.sh === id: cord-292985-w62xaa4f author: Römer, Rudolf A. title: Flexibility and mobility of SARS-CoV-2-related protein structures date: 2020-07-12 pages: extension: .txt txt: ./txt/cord-292985-w62xaa4f.txt cache: ./cache/cord-292985-w62xaa4f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-292985-w62xaa4f.txt' === file2bib.sh === id: cord-297826-2nruf2g7 author: Tian, Jing-Hui title: SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-297826-2nruf2g7.txt cache: ./cache/cord-297826-2nruf2g7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297826-2nruf2g7.txt' === file2bib.sh === id: cord-297044-tpp40j0g author: Jin, Zhenming title: Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-297044-tpp40j0g.txt cache: ./cache/cord-297044-tpp40j0g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-297044-tpp40j0g.txt' === file2bib.sh === id: cord-290290-wyx9ib7s author: Sinegubova, Maria V. title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-290290-wyx9ib7s.txt cache: ./cache/cord-290290-wyx9ib7s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-290290-wyx9ib7s.txt' === file2bib.sh === id: cord-298326-f5q7j3iu author: Nick, Benjamin C. title: Identification of a critical horseshoe-shaped region in the nsp5 (Mpro, 3CLpro) protease interdomain loop (IDL) of coronavirus mouse hepatitis virus (MHV) date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-298326-f5q7j3iu.txt cache: ./cache/cord-298326-f5q7j3iu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298326-f5q7j3iu.txt' === file2bib.sh === id: cord-294275-pp0vlaye author: Li, Jingjing title: Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow date: 2020-06-03 pages: extension: .txt txt: ./txt/cord-294275-pp0vlaye.txt cache: ./cache/cord-294275-pp0vlaye.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-294275-pp0vlaye.txt' === file2bib.sh === id: cord-262470-nkql7h9x author: Muus, Christoph title: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells date: 2020-04-20 pages: extension: .txt txt: ./txt/cord-262470-nkql7h9x.txt cache: ./cache/cord-262470-nkql7h9x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-262470-nkql7h9x.txt' === file2bib.sh === id: cord-297684-9q3oopaz author: Dobaño, Carlota title: Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-297684-9q3oopaz.txt cache: ./cache/cord-297684-9q3oopaz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297684-9q3oopaz.txt' === file2bib.sh === id: cord-296237-i9cti2ok author: Díez, José-María title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-296237-i9cti2ok.txt cache: ./cache/cord-296237-i9cti2ok.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296237-i9cti2ok.txt' === file2bib.sh === id: cord-296187-nnv2e7gr author: Mulgaonkar, Nirmitee title: Bcr-Abl tyrosine kinase inhibitor imatinib as a potential drug for COVID-19 date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-296187-nnv2e7gr.txt cache: ./cache/cord-296187-nnv2e7gr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296187-nnv2e7gr.txt' === file2bib.sh === id: cord-297786-jz1d1m2e author: Hasan, Md. Mahbub title: Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-297786-jz1d1m2e.txt cache: ./cache/cord-297786-jz1d1m2e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297786-jz1d1m2e.txt' === file2bib.sh === id: cord-300707-k9uk14b3 author: Bouwman, Kim M. title: Multimerization- and glycosylation-dependent receptor binding of SARS-CoV-2 spike proteins date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-300707-k9uk14b3.txt cache: ./cache/cord-300707-k9uk14b3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300707-k9uk14b3.txt' === file2bib.sh === id: cord-296997-ba7f2mf3 author: Sikora, Mateusz title: Map of SARS-CoV-2 spike epitopes not shielded by glycans date: 2020-07-03 pages: extension: .txt txt: ./txt/cord-296997-ba7f2mf3.txt cache: ./cache/cord-296997-ba7f2mf3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296997-ba7f2mf3.txt' === file2bib.sh === id: cord-280025-4hmecfi0 author: Korber, B title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-280025-4hmecfi0.txt cache: ./cache/cord-280025-4hmecfi0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280025-4hmecfi0.txt' === file2bib.sh === id: cord-297747-kifqgskc author: Lupala, Cecylia S. title: Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein date: 2020-03-27 pages: extension: .txt txt: ./txt/cord-297747-kifqgskc.txt cache: ./cache/cord-297747-kifqgskc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-297747-kifqgskc.txt' === file2bib.sh === id: cord-302608-fw4pmaoc author: Huang, Jiao-Mei title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date: 2020-03-19 pages: extension: .txt txt: ./txt/cord-302608-fw4pmaoc.txt cache: ./cache/cord-302608-fw4pmaoc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302608-fw4pmaoc.txt' === file2bib.sh === id: cord-296649-h6oyjz56 author: Scherf-Clavel, Oliver title: Tissue Level Profiling of SARS-CoV-2 antivirals in mice to predict their effects: comparing Remdesivir’s active metabolite GS-441 524 vs. the clinically failed Hydroxychloroquine date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-296649-h6oyjz56.txt cache: ./cache/cord-296649-h6oyjz56.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-296649-h6oyjz56.txt' === file2bib.sh === id: cord-288644-ywaefpe8 author: Rodon, Jordi title: Pre-clinical search of SARS-CoV-2 inhibitors and their combinations in approved drugs to tackle COVID-19 pandemic date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-288644-ywaefpe8.txt cache: ./cache/cord-288644-ywaefpe8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288644-ywaefpe8.txt' === file2bib.sh === id: cord-303832-1kcqhgjw author: Dai, Manman title: Long-term survival of salmon-attached SARS-CoV-2 at 4°C as a potential source of transmission in seafood markets date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-303832-1kcqhgjw.txt cache: ./cache/cord-303832-1kcqhgjw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-303832-1kcqhgjw.txt' === file2bib.sh === id: cord-295257-iguhy1z8 author: Calcagnile, Matteo title: ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study date: 2020-04-24 pages: extension: .txt txt: ./txt/cord-295257-iguhy1z8.txt cache: ./cache/cord-295257-iguhy1z8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-295257-iguhy1z8.txt' === file2bib.sh === id: cord-307536-qeo5dfxg author: Feng, Ye title: Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-307536-qeo5dfxg.txt cache: ./cache/cord-307536-qeo5dfxg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307536-qeo5dfxg.txt' === file2bib.sh === id: cord-300194-nsp53lv6 author: Rath, Soumya Lipsa title: Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-300194-nsp53lv6.txt cache: ./cache/cord-300194-nsp53lv6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-300194-nsp53lv6.txt' === file2bib.sh === id: cord-301535-eui41zyg author: Chandler-Brown, Devon title: A Highly Scalable and Rapidly Deployable RNA Extraction-Free COVID-19 Assay by Quantitative Sanger Sequencing date: 2020-04-10 pages: extension: .txt txt: ./txt/cord-301535-eui41zyg.txt cache: ./cache/cord-301535-eui41zyg.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-301535-eui41zyg.txt' === file2bib.sh === id: cord-298242-iuskpoug author: Yu, Alvin title: A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-298242-iuskpoug.txt cache: ./cache/cord-298242-iuskpoug.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298242-iuskpoug.txt' === file2bib.sh === id: cord-305054-4d84b2g6 author: Liu, Yuan title: The selection of reference genome and the search for the origin of SARS-CoV-2 date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-305054-4d84b2g6.txt cache: ./cache/cord-305054-4d84b2g6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305054-4d84b2g6.txt' === file2bib.sh === id: cord-302146-51hof7it author: Cross, Thomas J. title: Sequence characterization and molecular modeling of clinically relevant variants of the SARS-CoV-2 main protease date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-302146-51hof7it.txt cache: ./cache/cord-302146-51hof7it.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-302146-51hof7it.txt' === file2bib.sh === id: cord-288824-sygnmiun author: Lam, SD title: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals date: 2020-08-19 pages: extension: .txt txt: ./txt/cord-288824-sygnmiun.txt cache: ./cache/cord-288824-sygnmiun.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-288824-sygnmiun.txt' === file2bib.sh === id: cord-301233-nenw0f81 author: Naydenova, Katerina title: Structural basis for the inhibition of the SARS-CoV-2 RNA-dependent RNA polymerase by favipiravir-RTP date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-301233-nenw0f81.txt cache: ./cache/cord-301233-nenw0f81.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-301233-nenw0f81.txt' === file2bib.sh === id: cord-302733-rfuyd041 author: Dellicour, Simon title: A phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages date: 2020-10-21 pages: extension: .txt txt: ./txt/cord-302733-rfuyd041.txt cache: ./cache/cord-302733-rfuyd041.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-302733-rfuyd041.txt' === file2bib.sh === id: cord-303069-ss6g3jkg author: Jakhar, Renu title: An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2 date: 2020-05-26 pages: extension: .txt txt: ./txt/cord-303069-ss6g3jkg.txt cache: ./cache/cord-303069-ss6g3jkg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303069-ss6g3jkg.txt' === file2bib.sh === id: cord-304544-tqtdjh2m author: Enes, Ak title: Transcriptional response of signalling pathways to SARS-CoV-2 infection in normal human bronchial epithelial cells date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-304544-tqtdjh2m.txt cache: ./cache/cord-304544-tqtdjh2m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-304544-tqtdjh2m.txt' === file2bib.sh === id: cord-305589-ofpna4k1 author: Schubert, Katharina title: SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation date: 2020-07-07 pages: extension: .txt txt: ./txt/cord-305589-ofpna4k1.txt cache: ./cache/cord-305589-ofpna4k1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-305589-ofpna4k1.txt' === file2bib.sh === id: cord-307504-cogk5kig author: Zhu, Yuanmei title: Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity date: 2020-03-28 pages: extension: .txt txt: ./txt/cord-307504-cogk5kig.txt cache: ./cache/cord-307504-cogk5kig.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307504-cogk5kig.txt' === file2bib.sh === id: cord-302160-4yfvspaq author: Ruetalo, Natalia title: Rapid and efficient inactivation of surface dried SARS-CoV-2 by UV-C irradiation date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-302160-4yfvspaq.txt cache: ./cache/cord-302160-4yfvspaq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-302160-4yfvspaq.txt' === file2bib.sh === id: cord-310752-zl2g9wqo author: Sato, Taku title: Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-310752-zl2g9wqo.txt cache: ./cache/cord-310752-zl2g9wqo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310752-zl2g9wqo.txt' === file2bib.sh === id: cord-302920-jkr438p9 author: Gasser, Romain title: Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-302920-jkr438p9.txt cache: ./cache/cord-302920-jkr438p9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-302920-jkr438p9.txt' === file2bib.sh === id: cord-308310-wtmjt3hf author: Zha, Lisha title: Development of a COVID-19 vaccine based on the receptor binding domain displayed on virus-like particles date: 2020-05-14 pages: extension: .txt txt: ./txt/cord-308310-wtmjt3hf.txt cache: ./cache/cord-308310-wtmjt3hf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-308310-wtmjt3hf.txt' === file2bib.sh === id: cord-304792-8sdxqmkb author: Khan, Md. Abdullah-Al-Kamran title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-304792-8sdxqmkb.txt cache: ./cache/cord-304792-8sdxqmkb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304792-8sdxqmkb.txt' === file2bib.sh === id: cord-309289-vm0k7hfx author: Rothan, Hussin A. title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-309289-vm0k7hfx.txt cache: ./cache/cord-309289-vm0k7hfx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309289-vm0k7hfx.txt' === file2bib.sh === id: cord-300847-ycuiso0g author: Li, Wei title: Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models date: 2020-06-02 pages: extension: .txt txt: ./txt/cord-300847-ycuiso0g.txt cache: ./cache/cord-300847-ycuiso0g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300847-ycuiso0g.txt' === file2bib.sh === id: cord-298172-iyxyennq author: Guo, Youjia title: Potent mouse monoclonal antibodies that block SARS-CoV-2 infection date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-298172-iyxyennq.txt cache: ./cache/cord-298172-iyxyennq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-298172-iyxyennq.txt' === file2bib.sh === id: cord-307242-e20gtx0z author: Jegouic, Sophie M. title: Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-307242-e20gtx0z.txt cache: ./cache/cord-307242-e20gtx0z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-307242-e20gtx0z.txt' === file2bib.sh === id: cord-310464-lkdkdque author: Rayko, Mikhail title: Quality control of low-frequency variants in SARS-CoV-2 genomes date: 2020-05-07 pages: extension: .txt txt: ./txt/cord-310464-lkdkdque.txt cache: ./cache/cord-310464-lkdkdque.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-310464-lkdkdque.txt' === file2bib.sh === id: cord-307701-fujejfwb author: Gaurav, Shubham title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date: 2020-06-07 pages: extension: .txt txt: ./txt/cord-307701-fujejfwb.txt cache: ./cache/cord-307701-fujejfwb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-307701-fujejfwb.txt' === file2bib.sh === id: cord-300078-svu06v9c author: Haghani, Milad title: Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCov literature date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-300078-svu06v9c.txt cache: ./cache/cord-300078-svu06v9c.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 1 resourceName b'cord-300078-svu06v9c.txt' === file2bib.sh === id: cord-311240-o0zyt2vb author: Motayo, Babatunde Olarenwaju title: Evolution and Genetic Diversity of SARSCoV-2 in Africa Using Whole Genome Sequences date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-311240-o0zyt2vb.txt cache: ./cache/cord-311240-o0zyt2vb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311240-o0zyt2vb.txt' === file2bib.sh === id: cord-314072-av3r7it7 author: Liu, Zhuoming title: Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization date: 2020-11-08 pages: extension: .txt txt: ./txt/cord-314072-av3r7it7.txt cache: ./cache/cord-314072-av3r7it7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-314072-av3r7it7.txt' === file2bib.sh === id: cord-309512-d8n9711b author: Bacus, Michael G. title: Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-309512-d8n9711b.txt cache: ./cache/cord-309512-d8n9711b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309512-d8n9711b.txt' === file2bib.sh === id: cord-306901-uuwgpuhw author: Roy, Sylvie title: Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-306901-uuwgpuhw.txt cache: ./cache/cord-306901-uuwgpuhw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-306901-uuwgpuhw.txt' === file2bib.sh === id: cord-312473-7i7efdp2 author: Sidhom, John-William title: Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-312473-7i7efdp2.txt cache: ./cache/cord-312473-7i7efdp2.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-312473-7i7efdp2.txt' === file2bib.sh === id: cord-311333-shvtfxog author: Fukumoto, Tatsuya title: Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-311333-shvtfxog.txt cache: ./cache/cord-311333-shvtfxog.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-311333-shvtfxog.txt' === file2bib.sh === id: cord-306924-dw35dlx3 author: Wohlers, Inken title: COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-306924-dw35dlx3.txt cache: ./cache/cord-306924-dw35dlx3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306924-dw35dlx3.txt' === file2bib.sh === id: cord-311214-eqwxkwqa author: Kumar, Roshan title: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date: 2020-04-16 pages: extension: .txt txt: ./txt/cord-311214-eqwxkwqa.txt cache: ./cache/cord-311214-eqwxkwqa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311214-eqwxkwqa.txt' === file2bib.sh === id: cord-303399-s1hbpvn7 author: Straus, Marco R. title: SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses date: 2019-08-31 pages: extension: .txt txt: ./txt/cord-303399-s1hbpvn7.txt cache: ./cache/cord-303399-s1hbpvn7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-303399-s1hbpvn7.txt' === file2bib.sh === id: cord-303868-aes92l6s author: Steffen, Tara L. title: The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera date: 2020-08-22 pages: extension: .txt txt: ./txt/cord-303868-aes92l6s.txt cache: ./cache/cord-303868-aes92l6s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-303868-aes92l6s.txt' === file2bib.sh === id: cord-313571-umcbulcw author: Martínez-Murcia, Antonio title: In silico design and validation of commercial kit GPS™ CoVID-19 dtec-RT-qPCR Test under criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012 date: 2020-05-05 pages: extension: .txt txt: ./txt/cord-313571-umcbulcw.txt cache: ./cache/cord-313571-umcbulcw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-313571-umcbulcw.txt' === file2bib.sh === id: cord-312524-ee5xw1r8 author: Moustafa, Ahmed M. title: Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread date: 2020-06-08 pages: extension: .txt txt: ./txt/cord-312524-ee5xw1r8.txt cache: ./cache/cord-312524-ee5xw1r8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312524-ee5xw1r8.txt' === file2bib.sh === id: cord-310230-9wfb43gt author: Ghorbani, Mahdi title: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations date: 2020-06-27 pages: extension: .txt txt: ./txt/cord-310230-9wfb43gt.txt cache: ./cache/cord-310230-9wfb43gt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310230-9wfb43gt.txt' === file2bib.sh === id: cord-313795-jr3n3uo9 author: McAuley, Julie L. title: Liquid chalk is an antiseptic against SARS-CoV-2 and influenza A respiratory viruses date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-313795-jr3n3uo9.txt cache: ./cache/cord-313795-jr3n3uo9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-313795-jr3n3uo9.txt' === file2bib.sh === id: cord-311114-ggcpsjk8 author: Radhakrishnan, Chandni title: Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-311114-ggcpsjk8.txt cache: ./cache/cord-311114-ggcpsjk8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311114-ggcpsjk8.txt' === file2bib.sh === id: cord-307811-6e3j0pn7 author: Hao, Wei title: Binding of the SARS-CoV-2 Spike Protein to Glycans date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-307811-6e3j0pn7.txt cache: ./cache/cord-307811-6e3j0pn7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-307811-6e3j0pn7.txt' === file2bib.sh === id: cord-312702-fruzsn26 author: Finch, Courtney L. title: Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) date: 2020-05-14 pages: extension: .txt txt: ./txt/cord-312702-fruzsn26.txt cache: ./cache/cord-312702-fruzsn26.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312702-fruzsn26.txt' === file2bib.sh === id: cord-311445-b6bc6vwd author: Bansal, Kanika title: Codon pattern reveals SARS-CoV-2 to be a monomorphic strain that emerged through recombination of replicase and envelope alleles of bat and pangolin origin date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-311445-b6bc6vwd.txt cache: ./cache/cord-311445-b6bc6vwd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311445-b6bc6vwd.txt' === file2bib.sh === id: cord-300272-95o8yd7h author: Thépaut, Michel title: DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-300272-95o8yd7h.txt cache: ./cache/cord-300272-95o8yd7h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300272-95o8yd7h.txt' === file2bib.sh === id: cord-305496-t8ykkekl author: Stone, E. Taylor title: Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-305496-t8ykkekl.txt cache: ./cache/cord-305496-t8ykkekl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305496-t8ykkekl.txt' === file2bib.sh === id: cord-314445-4cb4a9r5 author: McNamara, Ryan P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-314445-4cb4a9r5.txt cache: ./cache/cord-314445-4cb4a9r5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-314445-4cb4a9r5.txt' === file2bib.sh === id: cord-317523-idji1l0a author: Xu, Huanzhou title: SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-317523-idji1l0a.txt cache: ./cache/cord-317523-idji1l0a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317523-idji1l0a.txt' === file2bib.sh === id: cord-313805-6mnclfeg author: Suzuki, Yuichiro J. title: SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-313805-6mnclfeg.txt cache: ./cache/cord-313805-6mnclfeg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-313805-6mnclfeg.txt' === file2bib.sh === id: cord-315702-pn8247j2 author: Sahakijpijarn, Sawittree title: Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-315702-pn8247j2.txt cache: ./cache/cord-315702-pn8247j2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315702-pn8247j2.txt' === file2bib.sh === id: cord-313247-55loucvc author: Pipes, Lenore title: Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-313247-55loucvc.txt cache: ./cache/cord-313247-55loucvc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313247-55loucvc.txt' === file2bib.sh === id: cord-313215-diqfmitr author: Luo, Lei title: Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-313215-diqfmitr.txt cache: ./cache/cord-313215-diqfmitr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-313215-diqfmitr.txt' === file2bib.sh === id: cord-312305-ll29frwc author: Sun, Shihui title: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date: 2020-11-11 pages: extension: .txt txt: ./txt/cord-312305-ll29frwc.txt cache: ./cache/cord-312305-ll29frwc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312305-ll29frwc.txt' === file2bib.sh === id: cord-313505-2lr4xara author: Resende, Paola Cristina title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-313505-2lr4xara.txt cache: ./cache/cord-313505-2lr4xara.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-313505-2lr4xara.txt' === file2bib.sh === id: cord-311066-62edsbfc author: Cox, Brian J. title: Integration of viral transcriptome sequencing with structure and sequence motifs predicts novel regulatory elements in SARS-CoV-2 date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-311066-62edsbfc.txt cache: ./cache/cord-311066-62edsbfc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311066-62edsbfc.txt' === file2bib.sh === id: cord-311843-un6urdb1 author: Baray, Juwel Chandra title: BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-311843-un6urdb1.txt cache: ./cache/cord-311843-un6urdb1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-311843-un6urdb1.txt' === file2bib.sh === id: cord-312228-wbyqmvhs author: Xiao, Minfeng title: Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples date: 2020-03-19 pages: extension: .txt txt: ./txt/cord-312228-wbyqmvhs.txt cache: ./cache/cord-312228-wbyqmvhs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-312228-wbyqmvhs.txt' === file2bib.sh === id: cord-305858-gp1u4kh7 author: Song, Xiang title: High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients date: 2020-07-19 pages: extension: .txt txt: ./txt/cord-305858-gp1u4kh7.txt cache: ./cache/cord-305858-gp1u4kh7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-305858-gp1u4kh7.txt' === file2bib.sh === id: cord-314321-klb8oe9q author: Chen, Serena H. title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date: 2020-04-18 pages: extension: .txt txt: ./txt/cord-314321-klb8oe9q.txt cache: ./cache/cord-314321-klb8oe9q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314321-klb8oe9q.txt' === file2bib.sh === id: cord-309411-2dfiwo65 author: Paris, Kristina A. title: Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-309411-2dfiwo65.txt cache: ./cache/cord-309411-2dfiwo65.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309411-2dfiwo65.txt' === file2bib.sh === id: cord-323041-wf0hlhim author: Larsen, Mads Delbo title: Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19 date: 2020-05-18 pages: extension: .txt txt: ./txt/cord-323041-wf0hlhim.txt cache: ./cache/cord-323041-wf0hlhim.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-323041-wf0hlhim.txt' === file2bib.sh === id: cord-310017-c8rd714a author: Popa, Alexandra title: Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-310017-c8rd714a.txt cache: ./cache/cord-310017-c8rd714a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310017-c8rd714a.txt' === file2bib.sh === id: cord-310477-vniokol0 author: Pontes, Camila title: Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs date: 2020-08-21 pages: extension: .txt txt: ./txt/cord-310477-vniokol0.txt cache: ./cache/cord-310477-vniokol0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-310477-vniokol0.txt' === file2bib.sh === id: cord-292862-ezrkg0dc author: Myerson, Jacob W. title: Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment date: 2020-04-18 pages: extension: .txt txt: ./txt/cord-292862-ezrkg0dc.txt cache: ./cache/cord-292862-ezrkg0dc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-292862-ezrkg0dc.txt' === file2bib.sh === id: cord-321049-9ozn6il7 author: de Almeida, Paula Rodrigues title: SARS-CoV2 quantification using RT-dPCR: a faster and safer alternative to assist viral genomic copies assessment using RT-qPCR date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-321049-9ozn6il7.txt cache: ./cache/cord-321049-9ozn6il7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-321049-9ozn6il7.txt' === file2bib.sh === id: cord-318499-uihof6k6 author: Beddingfield, Brandon title: The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-318499-uihof6k6.txt cache: ./cache/cord-318499-uihof6k6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318499-uihof6k6.txt' === file2bib.sh === id: cord-312414-g5px0b65 author: Takagi, Akira title: An immunodominance hierarchy exists in CD8+ T cell responses to HLA-A*02:01-restricted epitopes identified from the non-structural polyprotein 1a of SARS-CoV-2 date: 2020-09-19 pages: extension: .txt txt: ./txt/cord-312414-g5px0b65.txt cache: ./cache/cord-312414-g5px0b65.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312414-g5px0b65.txt' === file2bib.sh === id: cord-314329-rzda8x62 author: Wells, Stephen A. title: Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure date: 2020-03-12 pages: extension: .txt txt: ./txt/cord-314329-rzda8x62.txt cache: ./cache/cord-314329-rzda8x62.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-314329-rzda8x62.txt' === file2bib.sh === id: cord-320054-wqpr8v3p author: Yuan, Xianlin title: The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes date: 2020-08-24 pages: extension: .txt txt: ./txt/cord-320054-wqpr8v3p.txt cache: ./cache/cord-320054-wqpr8v3p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320054-wqpr8v3p.txt' === file2bib.sh === id: cord-312999-3erodkv9 author: Hassan, Sk. Sarif title: Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2 date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-312999-3erodkv9.txt cache: ./cache/cord-312999-3erodkv9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-312999-3erodkv9.txt' === file2bib.sh === id: cord-323654-9nnjex9y author: Ramachandran, Ashwin title: Electric-field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2 date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-323654-9nnjex9y.txt cache: ./cache/cord-323654-9nnjex9y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-323654-9nnjex9y.txt' === file2bib.sh === id: cord-304356-jyp9gjh9 author: Grant, Rogan A. title: Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-304356-jyp9gjh9.txt cache: ./cache/cord-304356-jyp9gjh9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-304356-jyp9gjh9.txt' === file2bib.sh === id: cord-325432-geb4esu5 author: Bukreyeva, Natalya title: The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-325432-geb4esu5.txt cache: ./cache/cord-325432-geb4esu5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-325432-geb4esu5.txt' === file2bib.sh === id: cord-321027-64y43o0y author: Andreano, Emanuele title: Identification of neutralizing human monoclonal antibodies from Italian Covid-19 convalescent patients date: 2020-05-09 pages: extension: .txt txt: ./txt/cord-321027-64y43o0y.txt cache: ./cache/cord-321027-64y43o0y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-321027-64y43o0y.txt' === file2bib.sh === id: cord-319447-xanewi59 author: Sun, Jiya title: Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-319447-xanewi59.txt cache: ./cache/cord-319447-xanewi59.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-319447-xanewi59.txt' === file2bib.sh === id: cord-315760-9g8901v6 author: Teng, Xufei title: Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades date: 2020-08-30 pages: extension: .txt txt: ./txt/cord-315760-9g8901v6.txt cache: ./cache/cord-315760-9g8901v6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-315760-9g8901v6.txt' === file2bib.sh === id: cord-324251-wgtatr8v author: Joshi, Madhvi title: Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-324251-wgtatr8v.txt cache: ./cache/cord-324251-wgtatr8v.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-324251-wgtatr8v.txt' === file2bib.sh === id: cord-318253-vp22xd8p author: Parisi, Ortensia Ilaria title: “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-318253-vp22xd8p.txt cache: ./cache/cord-318253-vp22xd8p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318253-vp22xd8p.txt' === file2bib.sh === id: cord-315982-iuez41zj author: Achdout, Hagit title: COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-315982-iuez41zj.txt cache: ./cache/cord-315982-iuez41zj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-315982-iuez41zj.txt' === file2bib.sh === id: cord-320417-01l27d99 author: Wang, Hai-Long title: The emergence of inter-clade hybrid SARS-CoV-2 lineages revealed by 2D nucleotide variation mapping date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-320417-01l27d99.txt cache: ./cache/cord-320417-01l27d99.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320417-01l27d99.txt' === file2bib.sh === id: cord-309556-xv3413k1 author: Chow, Ryan D. title: The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date: 2020-04-15 pages: extension: .txt txt: ./txt/cord-309556-xv3413k1.txt cache: ./cache/cord-309556-xv3413k1.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-309556-xv3413k1.txt' === file2bib.sh === id: cord-324892-mg2dziuw author: Carneiro, João title: CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2 date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-324892-mg2dziuw.txt cache: ./cache/cord-324892-mg2dziuw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324892-mg2dziuw.txt' === file2bib.sh === id: cord-321050-yabt72jf author: Tuttle, Kathryn D. title: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-321050-yabt72jf.txt cache: ./cache/cord-321050-yabt72jf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321050-yabt72jf.txt' === file2bib.sh === id: cord-323828-ug2duzw1 author: Ni, Dongchun title: Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-323828-ug2duzw1.txt cache: ./cache/cord-323828-ug2duzw1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323828-ug2duzw1.txt' === file2bib.sh === id: cord-323908-8dgngwmw author: He, Zhesheng title: Molecules inhibit the enzyme activity of 3-chymotrypsin-like cysteine protease of SARS-CoV-2 virus: the experimental and theory studies date: 2020-05-31 pages: extension: .txt txt: ./txt/cord-323908-8dgngwmw.txt cache: ./cache/cord-323908-8dgngwmw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-323908-8dgngwmw.txt' === file2bib.sh === id: cord-322654-6nccarjn author: Luzes, Rafael title: Angiotensin-(3–4) modulates angiotensin converting enzyme 2 (ACE2) downregulation in proximal tubule cells due to overweight and undernutrition: implications regarding the severity of renal lesions in Covid-19 infection date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-322654-6nccarjn.txt cache: ./cache/cord-322654-6nccarjn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-322654-6nccarjn.txt' === file2bib.sh === id: cord-317123-0tdfvlqd author: Tan, Xiaotian title: Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples date: 2020-04-21 pages: extension: .txt txt: ./txt/cord-317123-0tdfvlqd.txt cache: ./cache/cord-317123-0tdfvlqd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-317123-0tdfvlqd.txt' === file2bib.sh === id: cord-319100-3gdawhfn author: Kirkland, P.D. title: The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2 and other viruses date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-319100-3gdawhfn.txt cache: ./cache/cord-319100-3gdawhfn.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-319100-3gdawhfn.txt' === file2bib.sh === id: cord-324480-7u5lh4jx author: Sharma, A. title: Structural stability of SARS-CoV-2 degrades with temperature date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-324480-7u5lh4jx.txt cache: ./cache/cord-324480-7u5lh4jx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324480-7u5lh4jx.txt' === file2bib.sh === id: cord-321427-bwcpd6im author: Yee, Min title: Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-321427-bwcpd6im.txt cache: ./cache/cord-321427-bwcpd6im.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321427-bwcpd6im.txt' === file2bib.sh === id: cord-321155-dty18esg author: Zhang, Rongxin title: Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2 date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-321155-dty18esg.txt cache: ./cache/cord-321155-dty18esg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-321155-dty18esg.txt' === file2bib.sh === id: cord-320490-3jmo35jc author: Ismail, Saba title: Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine date: 2020-04-12 pages: extension: .txt txt: ./txt/cord-320490-3jmo35jc.txt cache: ./cache/cord-320490-3jmo35jc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-320490-3jmo35jc.txt' === file2bib.sh === id: cord-322942-y4zd2oui author: Olagnier, David title: Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate date: 2020-07-17 pages: extension: .txt txt: ./txt/cord-322942-y4zd2oui.txt cache: ./cache/cord-322942-y4zd2oui.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322942-y4zd2oui.txt' === file2bib.sh === id: cord-321369-xzu2faol author: Andreano, Emanuele title: Extremely potent human monoclonal antibodies from convalescent Covid-19 patients date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-321369-xzu2faol.txt cache: ./cache/cord-321369-xzu2faol.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-321369-xzu2faol.txt' === file2bib.sh === id: cord-327520-qj7coqfr author: Wei, Yulong title: Coronavirus genomes carry the signatures of their habitats date: 2020-06-13 pages: extension: .txt txt: ./txt/cord-327520-qj7coqfr.txt cache: ./cache/cord-327520-qj7coqfr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-327520-qj7coqfr.txt' === file2bib.sh === id: cord-324888-oak27okj author: Leng, Ling title: Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis date: 2020-04-18 pages: extension: .txt txt: ./txt/cord-324888-oak27okj.txt cache: ./cache/cord-324888-oak27okj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-324888-oak27okj.txt' === file2bib.sh === id: cord-325420-e9fjo7tl author: Xiao, Xia title: Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2 date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-325420-e9fjo7tl.txt cache: ./cache/cord-325420-e9fjo7tl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325420-e9fjo7tl.txt' === file2bib.sh === id: cord-326380-9ecsp66y author: Griesemer, Sara B title: Assessment of sample pooling for clinical SARS-CoV-2 testing date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-326380-9ecsp66y.txt cache: ./cache/cord-326380-9ecsp66y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326380-9ecsp66y.txt' === file2bib.sh === id: cord-308428-zw26usmh author: Walter, Justin D. title: Highly potent bispecific sybodies neutralize SARS-CoV-2 date: 2020-11-10 pages: extension: .txt txt: ./txt/cord-308428-zw26usmh.txt cache: ./cache/cord-308428-zw26usmh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-308428-zw26usmh.txt' === file2bib.sh === id: cord-313910-bwe2f7xf author: Bojadzic, Damir title: Small-Molecule In Vitro Inhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-313910-bwe2f7xf.txt cache: ./cache/cord-313910-bwe2f7xf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-313910-bwe2f7xf.txt' === file2bib.sh === id: cord-312038-g76cpjp7 author: Brunaugh, Ashlee D. title: Broad-Spectrum, Patient-Adaptable Inhaled Niclosamide-Lysozyme Particles are Efficacious Against Coronaviruses in Lethal Murine Infection Models date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-312038-g76cpjp7.txt cache: ./cache/cord-312038-g76cpjp7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-312038-g76cpjp7.txt' === file2bib.sh === id: cord-323839-a4oejky0 author: Sasaki, Michihito title: SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-323839-a4oejky0.txt cache: ./cache/cord-323839-a4oejky0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323839-a4oejky0.txt' === file2bib.sh === id: cord-326736-jd6fvaop author: Bosco-Lauth, Angela M. title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-326736-jd6fvaop.txt cache: ./cache/cord-326736-jd6fvaop.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326736-jd6fvaop.txt' === file2bib.sh === id: cord-318444-sgm24q1i author: Walter, Justin D. title: Sybodies targeting the SARS-CoV-2 receptor-binding domain date: 2020-05-16 pages: extension: .txt txt: ./txt/cord-318444-sgm24q1i.txt cache: ./cache/cord-318444-sgm24q1i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-318444-sgm24q1i.txt' === file2bib.sh === id: cord-328073-bqeffvzl author: Limonta, Daniel title: Nodosome inhibition as a novel broad-spectrum antiviral strategy against arboviruses and SARS-CoV-2 date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-328073-bqeffvzl.txt cache: ./cache/cord-328073-bqeffvzl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328073-bqeffvzl.txt' === file2bib.sh === id: cord-318478-fn0gcxbb author: Ziv, Omer title: The short- and long-range RNA-RNA Interactome of SARS-CoV-2 date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-318478-fn0gcxbb.txt cache: ./cache/cord-318478-fn0gcxbb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-318478-fn0gcxbb.txt' === file2bib.sh === id: cord-326866-nbd4arhx author: Fox, Charles W. title: The representation of women as authors of submissions to ecology journals during the COVID-19 pandemic date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-326866-nbd4arhx.txt cache: ./cache/cord-326866-nbd4arhx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326866-nbd4arhx.txt' === file2bib.sh === id: cord-326282-uxn64olw author: Lu, Maolin title: Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles date: 2020-09-13 pages: extension: .txt txt: ./txt/cord-326282-uxn64olw.txt cache: ./cache/cord-326282-uxn64olw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326282-uxn64olw.txt' === file2bib.sh === id: cord-323685-gjocoa60 author: Tsai, Shang-Jui title: Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-323685-gjocoa60.txt cache: ./cache/cord-323685-gjocoa60.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323685-gjocoa60.txt' === file2bib.sh === id: cord-325610-n3zb36am author: Postlethwait, John H. title: An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-325610-n3zb36am.txt cache: ./cache/cord-325610-n3zb36am.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325610-n3zb36am.txt' === file2bib.sh === id: cord-328636-1q71gjwt author: Arora, Kajal title: Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-328636-1q71gjwt.txt cache: ./cache/cord-328636-1q71gjwt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-328636-1q71gjwt.txt' === file2bib.sh === id: cord-326666-melz5fq4 author: Sun, Weitao title: The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe date: 2020-09-03 pages: extension: .txt txt: ./txt/cord-326666-melz5fq4.txt cache: ./cache/cord-326666-melz5fq4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326666-melz5fq4.txt' === file2bib.sh === id: cord-325348-yi6yu5l1 author: Zhang, G. title: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD date: 2020-06-17 pages: extension: .txt txt: ./txt/cord-325348-yi6yu5l1.txt cache: ./cache/cord-325348-yi6yu5l1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-325348-yi6yu5l1.txt' === file2bib.sh === id: cord-326337-s0fp5z1q author: Chan, Kui K. title: An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants date: 2020-10-19 pages: extension: .txt txt: ./txt/cord-326337-s0fp5z1q.txt cache: ./cache/cord-326337-s0fp5z1q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-326337-s0fp5z1q.txt' === file2bib.sh === id: cord-324344-dxuabscn author: Zhao, Xuesen title: LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2 date: 2020-04-05 pages: extension: .txt txt: ./txt/cord-324344-dxuabscn.txt cache: ./cache/cord-324344-dxuabscn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-324344-dxuabscn.txt' === file2bib.sh === id: cord-322955-7dw32xby author: Kathwate, Gunderao H title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date: 2020-06-12 pages: extension: .txt txt: ./txt/cord-322955-7dw32xby.txt cache: ./cache/cord-322955-7dw32xby.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-322955-7dw32xby.txt' === file2bib.sh === id: cord-325473-hrdanbn1 author: Ghahremanpour, Mohammad M. title: Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2 date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-325473-hrdanbn1.txt cache: ./cache/cord-325473-hrdanbn1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325473-hrdanbn1.txt' === file2bib.sh === id: cord-326882-bbn1tfq5 author: Li, Quan title: Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-326882-bbn1tfq5.txt cache: ./cache/cord-326882-bbn1tfq5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326882-bbn1tfq5.txt' === file2bib.sh === id: cord-327431-dnppshnv author: Hognon, Cécilia title: Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-327431-dnppshnv.txt cache: ./cache/cord-327431-dnppshnv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-327431-dnppshnv.txt' === file2bib.sh === id: cord-330473-f03ka7bd author: Yuan, Meng title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV date: 2020-03-14 pages: extension: .txt txt: ./txt/cord-330473-f03ka7bd.txt cache: ./cache/cord-330473-f03ka7bd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-330473-f03ka7bd.txt' === file2bib.sh === id: cord-330031-c1n994j6 author: Kratzel, Annika title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols date: 2020-03-17 pages: extension: .txt txt: ./txt/cord-330031-c1n994j6.txt cache: ./cache/cord-330031-c1n994j6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-330031-c1n994j6.txt' === file2bib.sh === id: cord-326441-w8iyh59u author: Bhattacharjee, Sayan title: Transmission of allosteric response within the homotrimer of SARS-CoV-2 spike upon recognition of ACE2 receptor by the receptor-binding domain date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-326441-w8iyh59u.txt cache: ./cache/cord-326441-w8iyh59u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326441-w8iyh59u.txt' === file2bib.sh === id: cord-327808-k3jec87p author: Zhu, Yunkai title: The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission date: 2020-08-25 pages: extension: .txt txt: ./txt/cord-327808-k3jec87p.txt cache: ./cache/cord-327808-k3jec87p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-327808-k3jec87p.txt' === file2bib.sh === id: cord-317628-1inxq7t5 author: Cuccarese, Michael F. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 pages: extension: .txt txt: ./txt/cord-317628-1inxq7t5.txt cache: ./cache/cord-317628-1inxq7t5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-317628-1inxq7t5.txt' === file2bib.sh === id: cord-328189-jpkxjn6e author: Brielle, Esther S. title: The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor date: 2020-03-12 pages: extension: .txt txt: ./txt/cord-328189-jpkxjn6e.txt cache: ./cache/cord-328189-jpkxjn6e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328189-jpkxjn6e.txt' === file2bib.sh === id: cord-329118-0gq5yusk author: Xiang, Boyu title: ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway date: 2020-06-06 pages: extension: .txt txt: ./txt/cord-329118-0gq5yusk.txt cache: ./cache/cord-329118-0gq5yusk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-329118-0gq5yusk.txt' === file2bib.sh === id: cord-323967-2mo915u1 author: Miersch, Shane title: Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations date: 2020-11-01 pages: extension: .txt txt: ./txt/cord-323967-2mo915u1.txt cache: ./cache/cord-323967-2mo915u1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-323967-2mo915u1.txt' === file2bib.sh === id: cord-320165-1b6sycgv author: Guo, Qirui title: Small molecules inhibit SARS-COV-2 induced aberrant inflammation and viral replication in mice by targeting S100A8/A9-TLR4 axis date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-320165-1b6sycgv.txt cache: ./cache/cord-320165-1b6sycgv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-320165-1b6sycgv.txt' === file2bib.sh === id: cord-328695-nptfd6c2 author: Tengs, Torstein title: A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-328695-nptfd6c2.txt cache: ./cache/cord-328695-nptfd6c2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328695-nptfd6c2.txt' === file2bib.sh === id: cord-331701-izkz1hz4 author: Eden, John-Sebastian title: An emergent clade of SARS-CoV-2 linked to returned travellers from Iran date: 2020-03-17 pages: extension: .txt txt: ./txt/cord-331701-izkz1hz4.txt cache: ./cache/cord-331701-izkz1hz4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-331701-izkz1hz4.txt' === file2bib.sh === id: cord-325124-0hxan9rw author: Li, Chenyu title: Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing date: 2020-05-18 pages: extension: .txt txt: ./txt/cord-325124-0hxan9rw.txt cache: ./cache/cord-325124-0hxan9rw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-325124-0hxan9rw.txt' === file2bib.sh === id: cord-328585-1rkrrx8a author: Lu, Shuai title: The immunodominant and neutralization linear epitopes for SARS-CoV-2 date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-328585-1rkrrx8a.txt cache: ./cache/cord-328585-1rkrrx8a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-328585-1rkrrx8a.txt' === file2bib.sh === id: cord-326257-rcv8sh22 author: Simmonds, P. title: Rampant C->U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses – causes and consequences for their short and long evolutionary trajectories date: 2020-05-01 pages: extension: .txt txt: ./txt/cord-326257-rcv8sh22.txt cache: ./cache/cord-326257-rcv8sh22.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-326257-rcv8sh22.txt' === file2bib.sh === id: cord-327711-welf0eb1 author: Zhou, Daming title: Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient date: 2020-06-13 pages: extension: .txt txt: ./txt/cord-327711-welf0eb1.txt cache: ./cache/cord-327711-welf0eb1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-327711-welf0eb1.txt' === file2bib.sh === id: cord-332178-0xyrmk5a author: Chadchan, Sangappa B. title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-332178-0xyrmk5a.txt cache: ./cache/cord-332178-0xyrmk5a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-332178-0xyrmk5a.txt' === file2bib.sh === id: cord-332134-88wfcc3y author: Li, Tingting title: A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection date: 2020-09-24 pages: extension: .txt txt: ./txt/cord-332134-88wfcc3y.txt cache: ./cache/cord-332134-88wfcc3y.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332134-88wfcc3y.txt' === file2bib.sh === id: cord-332185-a96r1k7a author: Zhang, Shuyuan title: Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-332185-a96r1k7a.txt cache: ./cache/cord-332185-a96r1k7a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-332185-a96r1k7a.txt' === file2bib.sh === id: cord-331611-pwj226j0 author: Shrimp, Jonathan H. title: An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19 date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-331611-pwj226j0.txt cache: ./cache/cord-331611-pwj226j0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-331611-pwj226j0.txt' === file2bib.sh === id: cord-329395-4k8js9v2 author: Ratcliff, Jeremy title: Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA date: 2020-07-01 pages: extension: .txt txt: ./txt/cord-329395-4k8js9v2.txt cache: ./cache/cord-329395-4k8js9v2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329395-4k8js9v2.txt' === file2bib.sh === id: cord-321166-nvphu1fm author: Thomson, Emma C. title: The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date: 2020-11-05 pages: extension: .txt txt: ./txt/cord-321166-nvphu1fm.txt cache: ./cache/cord-321166-nvphu1fm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-321166-nvphu1fm.txt' === file2bib.sh === id: cord-328257-kl4wh2zg author: Xu, H title: Hydroxychloroquine increased psychiatric-like behaviors and disrupted the expression of related genes in the mouse brain date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-328257-kl4wh2zg.txt cache: ./cache/cord-328257-kl4wh2zg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328257-kl4wh2zg.txt' === file2bib.sh === id: cord-328187-9zd79gai author: Zhang, Yali title: Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-328187-9zd79gai.txt cache: ./cache/cord-328187-9zd79gai.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-328187-9zd79gai.txt' === file2bib.sh === id: cord-329240-atisrhas author: Fedorenko, Aliza title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-329240-atisrhas.txt cache: ./cache/cord-329240-atisrhas.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-329240-atisrhas.txt' === file2bib.sh === id: cord-330213-reb9vo7x author: Miladi, Milad title: The landscape of SARS-CoV-2 RNA modifications date: 2020-07-18 pages: extension: .txt txt: ./txt/cord-330213-reb9vo7x.txt cache: ./cache/cord-330213-reb9vo7x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330213-reb9vo7x.txt' === file2bib.sh === id: cord-327912-wfjdxgxh author: Swann, Heather title: Minimal system for assembly of SARS-CoV-2 virus like particles date: 2020-08-24 pages: extension: .txt txt: ./txt/cord-327912-wfjdxgxh.txt cache: ./cache/cord-327912-wfjdxgxh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327912-wfjdxgxh.txt' === file2bib.sh === id: cord-328960-46zui1sl author: Hillen, Hauke S. title: Structure of replicating SARS-CoV-2 polymerase date: 2020-04-27 pages: extension: .txt txt: ./txt/cord-328960-46zui1sl.txt cache: ./cache/cord-328960-46zui1sl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328960-46zui1sl.txt' === file2bib.sh === id: cord-330384-yujbcwg5 author: Al-Mulla, Fahd title: A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine date: 2020-05-16 pages: extension: .txt txt: ./txt/cord-330384-yujbcwg5.txt cache: ./cache/cord-330384-yujbcwg5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330384-yujbcwg5.txt' === file2bib.sh === id: cord-329840-f3dsu36p author: Hati, Sanchita title: Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-329840-f3dsu36p.txt cache: ./cache/cord-329840-f3dsu36p.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329840-f3dsu36p.txt' === file2bib.sh === id: cord-329129-t84pu00z author: Zuo, J title: Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-329129-t84pu00z.txt cache: ./cache/cord-329129-t84pu00z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329129-t84pu00z.txt' === file2bib.sh === id: cord-334300-hnrmaytm author: Ventura Fernandes, Bianca H title: Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-334300-hnrmaytm.txt cache: ./cache/cord-334300-hnrmaytm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334300-hnrmaytm.txt' === file2bib.sh === id: cord-336012-8klkojpo author: Harilal, Divinlal title: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-336012-8klkojpo.txt cache: ./cache/cord-336012-8klkojpo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336012-8klkojpo.txt' === file2bib.sh === id: cord-338296-2hk7h132 author: Malla, Tek Narsingh title: Ebselen Reacts with SARS Coronavirus-2 Main Protease Crystals date: 2020-08-23 pages: extension: .txt txt: ./txt/cord-338296-2hk7h132.txt cache: ./cache/cord-338296-2hk7h132.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338296-2hk7h132.txt' === file2bib.sh === id: cord-332374-cbiw6yvb author: Israeli, Ofir title: Evaluating the efficacy of RT-qPCR SARS-CoV-2 direct approaches in comparison to RNA extraction date: 2020-06-10 pages: extension: .txt txt: ./txt/cord-332374-cbiw6yvb.txt cache: ./cache/cord-332374-cbiw6yvb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332374-cbiw6yvb.txt' === file2bib.sh === id: cord-329504-91te3nu8 author: Croll, Tristan title: Making the invisible enemy visible date: 2020-10-07 pages: extension: .txt txt: ./txt/cord-329504-91te3nu8.txt cache: ./cache/cord-329504-91te3nu8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329504-91te3nu8.txt' === file2bib.sh === id: cord-331888-lbtuvdv3 author: de Souza, Dalton Garcia Borges title: Forecasting COVID-19 cases at the Amazon region: a comparison of classical and machine learning models date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-331888-lbtuvdv3.txt cache: ./cache/cord-331888-lbtuvdv3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331888-lbtuvdv3.txt' === file2bib.sh === id: cord-336343-qbcb9qi3 author: Agarwal, Ajay title: in-silica Analysis of SARS-CoV-2 viral strain using Reverse Vaccinology Approach: A Case Study for USA date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-336343-qbcb9qi3.txt cache: ./cache/cord-336343-qbcb9qi3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336343-qbcb9qi3.txt' === file2bib.sh === id: cord-335652-v98gv5uf author: Salazar, Cecilia title: Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date: 2020-05-10 pages: extension: .txt txt: ./txt/cord-335652-v98gv5uf.txt cache: ./cache/cord-335652-v98gv5uf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-335652-v98gv5uf.txt' === file2bib.sh === id: cord-330743-o11d0aa1 author: Yu, Xi title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-330743-o11d0aa1.txt cache: ./cache/cord-330743-o11d0aa1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-330743-o11d0aa1.txt' === file2bib.sh === id: cord-322885-ob5euspo author: Durdagi, Serdar title: Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-322885-ob5euspo.txt cache: ./cache/cord-322885-ob5euspo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-322885-ob5euspo.txt' === file2bib.sh === id: cord-332539-v1bfm57x author: Gohl, Daryl M. title: A Rapid, Cost-Effective Tailed Amplicon Method for Sequencing SARS-CoV-2 date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-332539-v1bfm57x.txt cache: ./cache/cord-332539-v1bfm57x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332539-v1bfm57x.txt' === file2bib.sh === id: cord-329855-pr7g6ivu author: Kalfaoglu, Bahire title: T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis date: 2020-05-30 pages: extension: .txt txt: ./txt/cord-329855-pr7g6ivu.txt cache: ./cache/cord-329855-pr7g6ivu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-329855-pr7g6ivu.txt' === file2bib.sh === id: cord-334313-v2syspu6 author: Long, S. Wesley title: Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date: 2020-05-03 pages: extension: .txt txt: ./txt/cord-334313-v2syspu6.txt cache: ./cache/cord-334313-v2syspu6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334313-v2syspu6.txt' === file2bib.sh === id: cord-330337-d41imvo7 author: Basu, Souradip title: Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date: 2020-10-20 pages: extension: .txt txt: ./txt/cord-330337-d41imvo7.txt cache: ./cache/cord-330337-d41imvo7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-330337-d41imvo7.txt' === file2bib.sh === id: cord-336793-9bbyu1qx author: Matsuyama, Shutoku title: The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells date: 2020-08-24 pages: extension: .txt txt: ./txt/cord-336793-9bbyu1qx.txt cache: ./cache/cord-336793-9bbyu1qx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336793-9bbyu1qx.txt' === file2bib.sh === id: cord-331680-qlzhtxs0 author: Goryachev, A.N. title: Potential Opportunity of Antisense Therapy of COVID-19 on an in Vitro Model date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-331680-qlzhtxs0.txt cache: ./cache/cord-331680-qlzhtxs0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-331680-qlzhtxs0.txt' === file2bib.sh === id: cord-328644-odtue60a author: Comandatore, Francesco title: Insurgence and worldwide diffusion of genomic variants in SARS-CoV-2 genomes date: 2020-05-28 pages: extension: .txt txt: ./txt/cord-328644-odtue60a.txt cache: ./cache/cord-328644-odtue60a.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-328644-odtue60a.txt' === file2bib.sh === id: cord-335118-oa9jfots author: Taka, E. title: Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-335118-oa9jfots.txt cache: ./cache/cord-335118-oa9jfots.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-335118-oa9jfots.txt' === file2bib.sh === id: cord-334891-4jgtxg07 author: Choudhury, Abhigyan title: In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human date: 2020-11-11 pages: extension: .txt txt: ./txt/cord-334891-4jgtxg07.txt cache: ./cache/cord-334891-4jgtxg07.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334891-4jgtxg07.txt' === file2bib.sh === id: cord-340240-dk48pdqa author: Kuo, Tsun-Yung title: Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-340240-dk48pdqa.txt cache: ./cache/cord-340240-dk48pdqa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340240-dk48pdqa.txt' === file2bib.sh === id: cord-334220-sqvfr31q author: Messina, Francesco title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-334220-sqvfr31q.txt cache: ./cache/cord-334220-sqvfr31q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334220-sqvfr31q.txt' === file2bib.sh === id: cord-339720-d1stzy8w author: Zhao, Yuan title: Susceptibility of tree shrew to SARS-CoV-2 infection date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-339720-d1stzy8w.txt cache: ./cache/cord-339720-d1stzy8w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339720-d1stzy8w.txt' === file2bib.sh === id: cord-334624-chnibsa1 author: Hayn, Manuel title: Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-334624-chnibsa1.txt cache: ./cache/cord-334624-chnibsa1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334624-chnibsa1.txt' === file2bib.sh === id: cord-332271-slouuryl author: Baker, Jeremy D. title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease date: 2020-08-27 pages: extension: .txt txt: ./txt/cord-332271-slouuryl.txt cache: ./cache/cord-332271-slouuryl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-332271-slouuryl.txt' === file2bib.sh === id: cord-341768-k86gsfng author: Suresh, Voddu title: Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-341768-k86gsfng.txt cache: ./cache/cord-341768-k86gsfng.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341768-k86gsfng.txt' === file2bib.sh === id: cord-328659-miujzgtd author: Mishra, Akhilesh title: Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions date: 2020-07-27 pages: extension: .txt txt: ./txt/cord-328659-miujzgtd.txt cache: ./cache/cord-328659-miujzgtd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-328659-miujzgtd.txt' === file2bib.sh === id: cord-331786-wgt7kg6f author: Diego-Martin, Borja title: Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities date: 2020-10-13 pages: extension: .txt txt: ./txt/cord-331786-wgt7kg6f.txt cache: ./cache/cord-331786-wgt7kg6f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331786-wgt7kg6f.txt' === file2bib.sh === id: cord-336522-y9nzsv95 author: Rosenke, Kyle title: Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino-oligomers date: 2020-09-30 pages: extension: .txt txt: ./txt/cord-336522-y9nzsv95.txt cache: ./cache/cord-336522-y9nzsv95.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336522-y9nzsv95.txt' === file2bib.sh === id: cord-338734-laeocs3j author: Lima, Amorce title: Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-338734-laeocs3j.txt cache: ./cache/cord-338734-laeocs3j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338734-laeocs3j.txt' === file2bib.sh === id: cord-337701-56tmg38b author: Xiao, Yan title: Comparison of three TaqMan Real-Time Reverse Transcription-PCR assays in detecting SARS-CoV-2 date: 2020-07-06 pages: extension: .txt txt: ./txt/cord-337701-56tmg38b.txt cache: ./cache/cord-337701-56tmg38b.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-337701-56tmg38b.txt' === file2bib.sh === id: cord-334584-xh41koro author: Dilucca, Maddalena title: Temporal evolution and adaptation of SARS-COV 2 codon usage date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-334584-xh41koro.txt cache: ./cache/cord-334584-xh41koro.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334584-xh41koro.txt' === file2bib.sh === id: cord-339431-kyr5lv15 author: Saçar Demirci, Müşerref Duygu title: Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection date: 2020-03-17 pages: extension: .txt txt: ./txt/cord-339431-kyr5lv15.txt cache: ./cache/cord-339431-kyr5lv15.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339431-kyr5lv15.txt' === file2bib.sh === id: cord-336938-03366q9t author: Thacker, Vivek V title: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-336938-03366q9t.txt cache: ./cache/cord-336938-03366q9t.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-336938-03366q9t.txt' === file2bib.sh === id: cord-342657-od48cntc author: Klemm, Theresa title: Mechanism and inhibition of SARS-CoV-2 PLpro date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-342657-od48cntc.txt cache: ./cache/cord-342657-od48cntc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-342657-od48cntc.txt' === file2bib.sh === id: cord-337973-djqzgc1k author: Hao, Siyuan title: Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium date: 2020-08-28 pages: extension: .txt txt: ./txt/cord-337973-djqzgc1k.txt cache: ./cache/cord-337973-djqzgc1k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337973-djqzgc1k.txt' === file2bib.sh === id: cord-339772-q814d6l7 author: Pach, Szymon title: ACE2-Variants Indicate Potential SARS-CoV-2-Susceptibility in Animals: An Extensive Molecular Dynamics Study date: 2020-05-14 pages: extension: .txt txt: ./txt/cord-339772-q814d6l7.txt cache: ./cache/cord-339772-q814d6l7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-339772-q814d6l7.txt' === file2bib.sh === id: cord-335075-6wo2o5pp author: Bangaru, Sandhya title: Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate date: 2020-08-06 pages: extension: .txt txt: ./txt/cord-335075-6wo2o5pp.txt cache: ./cache/cord-335075-6wo2o5pp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-335075-6wo2o5pp.txt' === file2bib.sh === id: cord-338543-q6cl5kjp author: Salguero, Francisco J. title: Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19 date: 2020-09-17 pages: extension: .txt txt: ./txt/cord-338543-q6cl5kjp.txt cache: ./cache/cord-338543-q6cl5kjp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338543-q6cl5kjp.txt' === file2bib.sh === id: cord-336628-0evl3wnd author: Neufeldt, Christopher J. title: SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-336628-0evl3wnd.txt cache: ./cache/cord-336628-0evl3wnd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336628-0evl3wnd.txt' === file2bib.sh === id: cord-343586-28ezisog author: Rocca, María Florencia title: A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs date: 2020-05-07 pages: extension: .txt txt: ./txt/cord-343586-28ezisog.txt cache: ./cache/cord-343586-28ezisog.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343586-28ezisog.txt' === file2bib.sh === id: cord-340291-bah2ege0 author: Kohmer, Niko title: Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity date: 2020-05-10 pages: extension: .txt txt: ./txt/cord-340291-bah2ege0.txt cache: ./cache/cord-340291-bah2ege0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-340291-bah2ege0.txt' === file2bib.sh === id: cord-333420-qqyg9um9 author: Zhu, Xun title: idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates date: 2020-10-09 pages: extension: .txt txt: ./txt/cord-333420-qqyg9um9.txt cache: ./cache/cord-333420-qqyg9um9.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-333420-qqyg9um9.txt' === file2bib.sh === id: cord-342015-bz2vab6e author: Ouadfeul, Sid-Ali title: Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date: 2020-08-16 pages: extension: .txt txt: ./txt/cord-342015-bz2vab6e.txt cache: ./cache/cord-342015-bz2vab6e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342015-bz2vab6e.txt' === file2bib.sh === id: cord-329102-2y49kcwu author: Lan, Tammy C. T. title: Structure of the full SARS-CoV-2 RNA genome in infected cells date: 2020-06-30 pages: extension: .txt txt: ./txt/cord-329102-2y49kcwu.txt cache: ./cache/cord-329102-2y49kcwu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-329102-2y49kcwu.txt' === file2bib.sh === id: cord-346299-2s9j01q7 author: Salim Khan, S Muhammad title: Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-346299-2s9j01q7.txt cache: ./cache/cord-346299-2s9j01q7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346299-2s9j01q7.txt' === file2bib.sh === id: cord-333703-1ku3jc9s author: Kraus, Aurora title: A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date: 2020-11-08 pages: extension: .txt txt: ./txt/cord-333703-1ku3jc9s.txt cache: ./cache/cord-333703-1ku3jc9s.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333703-1ku3jc9s.txt' === file2bib.sh === id: cord-347441-8ow952d8 author: Parvez, Md Sorwer Alam title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism date: 2020-06-07 pages: extension: .txt txt: ./txt/cord-347441-8ow952d8.txt cache: ./cache/cord-347441-8ow952d8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347441-8ow952d8.txt' === file2bib.sh === id: cord-344560-662pfa61 author: Yamamoto, Norio title: Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro date: 2020-04-08 pages: extension: .txt txt: ./txt/cord-344560-662pfa61.txt cache: ./cache/cord-344560-662pfa61.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344560-662pfa61.txt' === file2bib.sh === id: cord-342942-1s32o9m8 author: Stamatakis, George title: Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases date: 2020-06-22 pages: extension: .txt txt: ./txt/cord-342942-1s32o9m8.txt cache: ./cache/cord-342942-1s32o9m8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342942-1s32o9m8.txt' === file2bib.sh === id: cord-333089-ufyzqgqk author: Aguilar-Pineda, Jorge Alberto title: Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-333089-ufyzqgqk.txt cache: ./cache/cord-333089-ufyzqgqk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-333089-ufyzqgqk.txt' === file2bib.sh === id: cord-336560-m5u6ryy9 author: Boudewijns, Robbert title: STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-336560-m5u6ryy9.txt cache: ./cache/cord-336560-m5u6ryy9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336560-m5u6ryy9.txt' === file2bib.sh === id: cord-340432-vm6m0kb4 author: Srivastava, Sukrit title: Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-340432-vm6m0kb4.txt cache: ./cache/cord-340432-vm6m0kb4.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-340432-vm6m0kb4.txt' === file2bib.sh === id: cord-343476-0chuwvg6 author: MacLean, Oscar A. title: Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans date: 2020-05-29 pages: extension: .txt txt: ./txt/cord-343476-0chuwvg6.txt cache: ./cache/cord-343476-0chuwvg6.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343476-0chuwvg6.txt' === file2bib.sh === id: cord-338055-2d6n4cve author: Hassan, Sk. Sarif title: A unique view of SARS-CoV-2 through the lens of ORF8 protein date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-338055-2d6n4cve.txt cache: ./cache/cord-338055-2d6n4cve.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-338055-2d6n4cve.txt' === file2bib.sh === id: cord-335443-iv2gs3kg author: Kim, Youngchang title: Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 date: 2020-06-28 pages: extension: .txt txt: ./txt/cord-335443-iv2gs3kg.txt cache: ./cache/cord-335443-iv2gs3kg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-335443-iv2gs3kg.txt' === file2bib.sh === id: cord-345299-4k7qymqd author: Xiong, Hua-Long title: Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-345299-4k7qymqd.txt cache: ./cache/cord-345299-4k7qymqd.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-345299-4k7qymqd.txt' === file2bib.sh === id: cord-344236-qp3ianzf author: Ali, Fedaa title: ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity date: 2020-05-08 pages: extension: .txt txt: ./txt/cord-344236-qp3ianzf.txt cache: ./cache/cord-344236-qp3ianzf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-344236-qp3ianzf.txt' === file2bib.sh === id: cord-342010-5mkf67os author: Levasseur, Anthony title: Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients date: 2020-09-04 pages: extension: .txt txt: ./txt/cord-342010-5mkf67os.txt cache: ./cache/cord-342010-5mkf67os.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342010-5mkf67os.txt' === file2bib.sh === id: cord-348727-o38uplxe author: Beaudoin-Bussières, Guillaume title: Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-348727-o38uplxe.txt cache: ./cache/cord-348727-o38uplxe.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348727-o38uplxe.txt' === file2bib.sh === id: cord-343517-vf32wxkx author: Lokman, Syed Mohammad title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-343517-vf32wxkx.txt cache: ./cache/cord-343517-vf32wxkx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-343517-vf32wxkx.txt' === file2bib.sh === id: cord-347804-kxhasabe author: Luo, Ruibang title: Tracking cytosine depletion in SARS-CoV-2 date: 2020-10-26 pages: extension: .txt txt: ./txt/cord-347804-kxhasabe.txt cache: ./cache/cord-347804-kxhasabe.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-347804-kxhasabe.txt' === file2bib.sh === id: cord-339012-4juhmjaj author: Hou, Wei title: Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date: 2020-07-28 pages: extension: .txt txt: ./txt/cord-339012-4juhmjaj.txt cache: ./cache/cord-339012-4juhmjaj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339012-4juhmjaj.txt' === file2bib.sh === id: cord-344909-0o55l4iy author: Cross, Robert W. title: Use of convalescent serum reduces severity of COVID-19 in nonhuman primates date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-344909-0o55l4iy.txt cache: ./cache/cord-344909-0o55l4iy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344909-0o55l4iy.txt' === file2bib.sh === id: cord-341502-jlzufa28 author: Lee, Sungyul title: The SARS-CoV-2 RNA interactome date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-341502-jlzufa28.txt cache: ./cache/cord-341502-jlzufa28.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-341502-jlzufa28.txt' === file2bib.sh === id: cord-343317-97n1j0jj author: Duan, Xiaohua title: Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date: 2020-05-02 pages: extension: .txt txt: ./txt/cord-343317-97n1j0jj.txt cache: ./cache/cord-343317-97n1j0jj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343317-97n1j0jj.txt' === file2bib.sh === id: cord-342456-5gp3cry0 author: Hoagland, Daisy A. title: Modulating the transcriptional landscape of SARS-CoV-2 as an effective method for developing antiviral compounds date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-342456-5gp3cry0.txt cache: ./cache/cord-342456-5gp3cry0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-342456-5gp3cry0.txt' === file2bib.sh === id: cord-334394-qgyzk7th author: Edgar, Robert C. title: Petabase-scale sequence alignment catalyses viral discovery date: 2020-08-10 pages: extension: .txt txt: ./txt/cord-334394-qgyzk7th.txt cache: ./cache/cord-334394-qgyzk7th.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-334394-qgyzk7th.txt' === file2bib.sh === id: cord-348635-1pb2ag9j author: Anand, Praveen title: SARS-CoV-2 selectively mimics a cleavable peptide of human ENaC in a strategic hijack of host proteolytic machinery date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-348635-1pb2ag9j.txt cache: ./cache/cord-348635-1pb2ag9j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-348635-1pb2ag9j.txt' === file2bib.sh === id: cord-339665-nwwutduy author: Patel, Ami title: Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date: 2020-07-29 pages: extension: .txt txt: ./txt/cord-339665-nwwutduy.txt cache: ./cache/cord-339665-nwwutduy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-339665-nwwutduy.txt' === file2bib.sh === id: cord-346532-4xpnd93d author: Strömich, Léonie title: Allosteric Hotspots in the Main Protease of SARS-CoV-2 date: 2020-11-06 pages: extension: .txt txt: ./txt/cord-346532-4xpnd93d.txt cache: ./cache/cord-346532-4xpnd93d.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346532-4xpnd93d.txt' === file2bib.sh === id: cord-342599-558yn6pu author: Rinchai, Darawan title: A modular framework for the development of targeted Covid-19 blood transcript profiling panels date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-342599-558yn6pu.txt cache: ./cache/cord-342599-558yn6pu.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-342599-558yn6pu.txt' === file2bib.sh === id: cord-346335-el45v0a5 author: Tan, H.S. title: Fourier spectral density of the coronavirus genome date: 2020-08-11 pages: extension: .txt txt: ./txt/cord-346335-el45v0a5.txt cache: ./cache/cord-346335-el45v0a5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346335-el45v0a5.txt' === file2bib.sh === id: cord-347714-vxxhglx7 author: Abitogun, Folagbade title: COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-347714-vxxhglx7.txt cache: ./cache/cord-347714-vxxhglx7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347714-vxxhglx7.txt' === file2bib.sh === id: cord-347982-omxcdiwt author: Basso, Fernanda Gisele title: Cooperative efforts on developing vaccines and therapies for COVID-19 Cooperative efforts for COVID-19 date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-347982-omxcdiwt.txt cache: ./cache/cord-347982-omxcdiwt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-347982-omxcdiwt.txt' === file2bib.sh === id: cord-349015-5oisrm5s author: Liu, Zhe title: Identification of a common deletion in the spike protein of SARS-CoV-2 date: 2020-04-02 pages: extension: .txt txt: ./txt/cord-349015-5oisrm5s.txt cache: ./cache/cord-349015-5oisrm5s.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349015-5oisrm5s.txt' === file2bib.sh === id: cord-345405-ngpsgn63 author: Tremiliosi, Guilherme C. title: Ag nanoparticles-based antimicrobial polycotton fabrics to prevent the transmission and spread of SARS-CoV-2 date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-345405-ngpsgn63.txt cache: ./cache/cord-345405-ngpsgn63.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-345405-ngpsgn63.txt' === file2bib.sh === id: cord-348159-v5hrcl5k author: Sang, Eric R. title: Epigenetic Evolution of ACE2 and IL-6 Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-348159-v5hrcl5k.txt cache: ./cache/cord-348159-v5hrcl5k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-348159-v5hrcl5k.txt' === file2bib.sh === id: cord-345499-hq5um68k author: Xiong, Rui title: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 date: 2020-03-12 pages: extension: .txt txt: ./txt/cord-345499-hq5um68k.txt cache: ./cache/cord-345499-hq5um68k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-345499-hq5um68k.txt' === file2bib.sh === id: cord-350627-4pgish5x author: Zhao, Yu title: Single-cell RNA expression profiling of ACE2,thereceptor of SARS-CoV-2 date: 2020-01-26 pages: extension: .txt txt: ./txt/cord-350627-4pgish5x.txt cache: ./cache/cord-350627-4pgish5x.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350627-4pgish5x.txt' === file2bib.sh === id: cord-351472-ch004jxy author: Vashi, Yoya title: Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens date: 2020-04-10 pages: extension: .txt txt: ./txt/cord-351472-ch004jxy.txt cache: ./cache/cord-351472-ch004jxy.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351472-ch004jxy.txt' === file2bib.sh === id: cord-344949-9zyz4hll author: Luban, Jeremy title: The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines date: 2020-08-05 pages: extension: .txt txt: ./txt/cord-344949-9zyz4hll.txt cache: ./cache/cord-344949-9zyz4hll.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-344949-9zyz4hll.txt' === file2bib.sh === id: cord-348729-kejlm425 author: Liu, Xiaoyu title: Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection date: 2020-05-04 pages: extension: .txt txt: ./txt/cord-348729-kejlm425.txt cache: ./cache/cord-348729-kejlm425.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-348729-kejlm425.txt' === file2bib.sh === id: cord-340516-9dfaqsv7 author: Moore, Anne C. title: Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-340516-9dfaqsv7.txt cache: ./cache/cord-340516-9dfaqsv7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-340516-9dfaqsv7.txt' === file2bib.sh === id: cord-351559-az4pgi9k author: Turjya, Rafeed Rahman title: Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date: 2020-06-29 pages: extension: .txt txt: ./txt/cord-351559-az4pgi9k.txt cache: ./cache/cord-351559-az4pgi9k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-351559-az4pgi9k.txt' === file2bib.sh === id: cord-343027-ks3fn9pq author: Fraser, Nicholas title: Preprinting the COVID-19 pandemic date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-343027-ks3fn9pq.txt cache: ./cache/cord-343027-ks3fn9pq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-343027-ks3fn9pq.txt' === file2bib.sh === id: cord-349794-mhviub6e author: Le, Brian L. title: Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 date: 2020-10-23 pages: extension: .txt txt: ./txt/cord-349794-mhviub6e.txt cache: ./cache/cord-349794-mhviub6e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349794-mhviub6e.txt' === file2bib.sh === id: cord-346546-yffwd0dc author: Douangamath, Alice title: Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-346546-yffwd0dc.txt cache: ./cache/cord-346546-yffwd0dc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346546-yffwd0dc.txt' === file2bib.sh === id: cord-353742-k4gxww2c author: Arévalo, AP title: Ivermectin reduces coronavirus infection in vivo: a mouse experimental model date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-353742-k4gxww2c.txt cache: ./cache/cord-353742-k4gxww2c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353742-k4gxww2c.txt' === file2bib.sh === id: cord-352073-rdhjj72g author: Taniwaki, S.A title: Resource optimization in COVID-19 diagnosis date: 2020-06-26 pages: extension: .txt txt: ./txt/cord-352073-rdhjj72g.txt cache: ./cache/cord-352073-rdhjj72g.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-352073-rdhjj72g.txt' === file2bib.sh === id: cord-353554-98uzivsk author: Zhang, Zheng title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors date: 2018-03-08 pages: extension: .txt txt: ./txt/cord-353554-98uzivsk.txt cache: ./cache/cord-353554-98uzivsk.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353554-98uzivsk.txt' === file2bib.sh === id: cord-353099-38bz0acw author: Tang, Mei San title: Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-353099-38bz0acw.txt cache: ./cache/cord-353099-38bz0acw.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353099-38bz0acw.txt' === file2bib.sh === id: cord-350821-0qfoc553 author: Jahromi, Reza title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 date: 2020-06-01 pages: extension: .txt txt: ./txt/cord-350821-0qfoc553.txt cache: ./cache/cord-350821-0qfoc553.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350821-0qfoc553.txt' === file2bib.sh === id: cord-346670-34wfy52f author: Gobeil, Sophie M-C. title: D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction date: 2020-10-12 pages: extension: .txt txt: ./txt/cord-346670-34wfy52f.txt cache: ./cache/cord-346670-34wfy52f.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346670-34wfy52f.txt' === file2bib.sh === id: cord-347472-n6811ens author: Rosebrock, Adam P. title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date: 2020-05-15 pages: extension: .txt txt: ./txt/cord-347472-n6811ens.txt cache: ./cache/cord-347472-n6811ens.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-347472-n6811ens.txt' === file2bib.sh === id: cord-353911-hp6s6ebh author: Petráš, Marek title: Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein date: 2020-11-03 pages: extension: .txt txt: ./txt/cord-353911-hp6s6ebh.txt cache: ./cache/cord-353911-hp6s6ebh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353911-hp6s6ebh.txt' === file2bib.sh === id: cord-353129-ivbf4kuq author: Faryami, Ahmad title: Open source 3D printed Ventilation Device date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-353129-ivbf4kuq.txt cache: ./cache/cord-353129-ivbf4kuq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353129-ivbf4kuq.txt' === file2bib.sh === id: cord-352943-ztonp62x author: Nagpal, Sunil title: What if we perceive SARS-CoV-2 genomes as documents? Topic modelling using Latent Dirichlet Allocation to identify mutation signatures and classify SARS-CoV-2 genomes date: 2020-08-20 pages: extension: .txt txt: ./txt/cord-352943-ztonp62x.txt cache: ./cache/cord-352943-ztonp62x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-352943-ztonp62x.txt' === file2bib.sh === id: cord-349364-vert186n author: Márquez-López, Cristina title: SARS-CoV-2 protein Nsp1 alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy-related PKP2 mutant date: 2020-09-14 pages: extension: .txt txt: ./txt/cord-349364-vert186n.txt cache: ./cache/cord-349364-vert186n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349364-vert186n.txt' === file2bib.sh === id: cord-353209-qkhfp66l author: Steiner, Daniel J. title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date: 2020-06-16 pages: extension: .txt txt: ./txt/cord-353209-qkhfp66l.txt cache: ./cache/cord-353209-qkhfp66l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353209-qkhfp66l.txt' === file2bib.sh === id: cord-355811-aq7p1uxo author: Węglarz-Tomczak, Ewelina title: Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-355811-aq7p1uxo.txt cache: ./cache/cord-355811-aq7p1uxo.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-355811-aq7p1uxo.txt' === file2bib.sh === id: cord-356005-zhwtlik6 author: Yazhini, Arangasamy title: D614G substitution enhances the stability of trimeric SARS-CoV-2 spike protein date: 2020-11-02 pages: extension: .txt txt: ./txt/cord-356005-zhwtlik6.txt cache: ./cache/cord-356005-zhwtlik6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356005-zhwtlik6.txt' === file2bib.sh === id: cord-349684-2tioh80m author: Pezzotti, Giuseppe title: Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride date: 2020-06-20 pages: extension: .txt txt: ./txt/cord-349684-2tioh80m.txt cache: ./cache/cord-349684-2tioh80m.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-349684-2tioh80m.txt' === file2bib.sh === id: cord-355728-wivk0bm0 author: Schoof, Michael title: An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation date: 2020-08-17 pages: extension: .txt txt: ./txt/cord-355728-wivk0bm0.txt cache: ./cache/cord-355728-wivk0bm0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-355728-wivk0bm0.txt' === file2bib.sh === id: cord-355758-tk7eturq author: Berrio, Alejandro title: Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function date: 2020-09-22 pages: extension: .txt txt: ./txt/cord-355758-tk7eturq.txt cache: ./cache/cord-355758-tk7eturq.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-355758-tk7eturq.txt' === file2bib.sh === id: cord-353731-7xn7m662 author: Heaton, Brook E. title: SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2 date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-353731-7xn7m662.txt cache: ./cache/cord-353731-7xn7m662.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353731-7xn7m662.txt' === file2bib.sh === id: cord-350558-qfdp4ov9 author: Shaban, Mohammed Samer title: Inhibiting coronavirus replication in cultured cells by chemical ER stress date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-350558-qfdp4ov9.txt cache: ./cache/cord-350558-qfdp4ov9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-350558-qfdp4ov9.txt' === file2bib.sh === id: cord-351321-6d2mn5ok author: Gouveia, Duarte title: Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-351321-6d2mn5ok.txt cache: ./cache/cord-351321-6d2mn5ok.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-351321-6d2mn5ok.txt' === file2bib.sh === id: cord-353777-t8q99tlq author: Jia, Yong title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date: 2020-04-11 pages: extension: .txt txt: ./txt/cord-353777-t8q99tlq.txt cache: ./cache/cord-353777-t8q99tlq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353777-t8q99tlq.txt' === file2bib.sh === id: cord-346978-ubkqny8j author: Ranoa, Diana Rose E. title: Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction date: 2020-06-18 pages: extension: .txt txt: ./txt/cord-346978-ubkqny8j.txt cache: ./cache/cord-346978-ubkqny8j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-346978-ubkqny8j.txt' === file2bib.sh === id: cord-353877-wzndpcq3 author: Albagi, Sahar Obi Abd title: A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach date: 2020-05-20 pages: extension: .txt txt: ./txt/cord-353877-wzndpcq3.txt cache: ./cache/cord-353877-wzndpcq3.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-353877-wzndpcq3.txt' === file2bib.sh === id: cord-354725-lqio7l8k author: Arumugam, Arunkumar title: A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings date: 2020-04-30 pages: extension: .txt txt: ./txt/cord-354725-lqio7l8k.txt cache: ./cache/cord-354725-lqio7l8k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354725-lqio7l8k.txt' === file2bib.sh === id: cord-354868-pqn59ojj author: Yao, Hebang title: A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2 date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-354868-pqn59ojj.txt cache: ./cache/cord-354868-pqn59ojj.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354868-pqn59ojj.txt' === file2bib.sh === id: cord-353161-mtq6yh25 author: Rodrigues, João PGLM title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling date: 2020-06-05 pages: extension: .txt txt: ./txt/cord-353161-mtq6yh25.txt cache: ./cache/cord-353161-mtq6yh25.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-353161-mtq6yh25.txt' === file2bib.sh === id: cord-350935-p6euuop3 author: Doğan, Tunca title: CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-350935-p6euuop3.txt cache: ./cache/cord-350935-p6euuop3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350935-p6euuop3.txt' === file2bib.sh === id: cord-351011-v4zmksio author: Golden, Joseph W. title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-351011-v4zmksio.txt cache: ./cache/cord-351011-v4zmksio.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-351011-v4zmksio.txt' === file2bib.sh === id: cord-350817-tmszrtju author: Hoepel, Willianne title: Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses date: 2020-07-13 pages: extension: .txt txt: ./txt/cord-350817-tmszrtju.txt cache: ./cache/cord-350817-tmszrtju.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-350817-tmszrtju.txt' === file2bib.sh === id: cord-356264-q0yqnlyl author: Armijos-Jaramillo, Vinicio title: SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability date: 2020-03-23 pages: extension: .txt txt: ./txt/cord-356264-q0yqnlyl.txt cache: ./cache/cord-356264-q0yqnlyl.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356264-q0yqnlyl.txt' === file2bib.sh === id: cord-356090-oj3d9ail author: Gorgun, D. title: Binding Mode of SARS-CoV2 Fusion Peptide to Human Cellular Membrane date: 2020-10-27 pages: extension: .txt txt: ./txt/cord-356090-oj3d9ail.txt cache: ./cache/cord-356090-oj3d9ail.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-356090-oj3d9ail.txt' === file2bib.sh === id: cord-355397-y69bk5jc author: Caruso, Ícaro P. title: Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism date: 2020-09-06 pages: extension: .txt txt: ./txt/cord-355397-y69bk5jc.txt cache: ./cache/cord-355397-y69bk5jc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-355397-y69bk5jc.txt' === file2bib.sh === id: cord-354315-yfn9vaan author: Meirson, Tomer title: Structural basis of SARS-CoV-2 spike protein induced by ACE2 date: 2020-05-24 pages: extension: .txt txt: ./txt/cord-354315-yfn9vaan.txt cache: ./cache/cord-354315-yfn9vaan.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-354315-yfn9vaan.txt' === file2bib.sh === id: cord-350286-n7ylgqfu author: Giri, Rajanish title: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date: 2020-04-03 pages: extension: .txt txt: ./txt/cord-350286-n7ylgqfu.txt cache: ./cache/cord-350286-n7ylgqfu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350286-n7ylgqfu.txt' Que is empty; done journal-biorxiv-cord === reduce.pl bib === id = cord-102219-d3gkfo7s author = Perzel Mandell, Kira A. title = Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date = 2019-10-30 pages = extension = .txt mime = text/plain words = 5038 sentences = 231 flesch = 47 summary = In the present report, we describe the use of whole genome bisulfite sequencing (WGBS) to capture an unbiased map of the DNAm landscape, and to characterize both CpG and CpH methylation during prenatal brain development. We performed whole genome bisulfite sequencing (WGBS) to better characterize the shifting DNAm landscape in the developing human dorsolateral prefrontal cortex (DLPFC) in 20 prenatal samples during the second trimester in utero (Table S1 ). We found that DNAm changes were abundant even during this relatively restricted period in prenatal development, with 36,546 CpG sites differentially methylated across the ages of 14-20 post-conception weeks (PCW, at FDR < 0.05, Table S3 ). The top biological processes associated with genes containing differentially methylated CpGs across age were related to axon development and guidance, and regulation of neuron projection ( Figure S4 , Table S8 ). cache = ./cache/cord-102219-d3gkfo7s.txt txt = ./txt/cord-102219-d3gkfo7s.txt === reduce.pl bib === id = cord-102178-ju826pao author = Carey, Clayton M. title = Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis date = 2020-03-30 pages = extension = .txt mime = text/plain words = 5255 sentences = 240 flesch = 46 summary = Under normal conditions, GC-C interacts with endogenous guanylin peptides to promote water secretion in the intestine, but signaling can be hijacked by bacterially-encoded heat-stable enterotoxins (STa) during infection, which leads to overstimulation of GC-C and diarrhea. Phylogenetic analysis in mammals revealed evidence of recurrent positive selection in the GC-C ligand-binding domain in primates and bats, consistent with selective pressures to evade interactions with STa. Using in vitro assays and transgenic intestinal organoids to model STa-mediated diarrhea, we show that GC-C diversification in these lineages results in substantial variation in toxin susceptibility. Under normal conditions, GC-C activity is stimulated by interactions with the endogenous peptides guanylin and uroguanylin, leading to an increase in intracellular cGMP levels in enterocytes lining the small intestine and colon 3 ( Figure 1A ). To test if rapid evolution of GC-C ligand-binding domains result in functional differences in STa susceptibility, we generated cell lines stably expressing GC-C from seven primate and five bat species. cache = ./cache/cord-102178-ju826pao.txt txt = ./txt/cord-102178-ju826pao.txt === reduce.pl bib === === reduce.pl bib === id = cord-102199-mc6zruyx author = Toksvang, Linea Natalie title = Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review date = 2019-01-30 pages = extension = .txt mime = text/plain words = 2340 sentences = 144 flesch = 40 summary = title: Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9–25% of the ALL patients in two of the four included RCTs using 6TG doses of 40–60 mg/m2/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children's Oncology Group CCG-1952 clinical trial 6-Thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension Splitting a therapeutic dose of thioguanine may avoid liver toxicity and be an efficacious treatment for severe inflammatory bowel disease: a 2-center observational cohort study Early nodular hyperplasia of the liver occurring with inflammatory bowel diseases in association with thioguanine therapy cache = ./cache/cord-102199-mc6zruyx.txt txt = ./txt/cord-102199-mc6zruyx.txt === reduce.pl bib === === reduce.pl bib === id = cord-102279-ena1usqv author = Long, Rory K. M. title = Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date = 2020-06-23 pages = extension = .txt mime = text/plain words = 3681 sentences = 275 flesch = 55 summary = projections of 3D STED image stacks show high intensity ERmoxGFP and Sec61β-GFP labeling in a 89 CER region and low intensity labeling in PER tubules in mock-infected cells ( Figure 1A ), as reported 90 previously by diffraction limited confocal microscopy (3). Density-based segmentation of the ERmoxGFP-96 and Sec61β-GFP-labelled ER of ZIKV-infected cells showed that the higher density crescent-shaped 97 CER region exhibited significant overlap with dsRNA-positive ER structures relative to the rest of 98 the ER ( Figure 1B ). Morphological comparison of the dsRNA-positive and -negative CER of 133 ZIKV-infected cells with the CER of mock-infected cells showed that the CER was composed of a 134 convoluted network of tubules for both the ERmoxGFP-and Sec61β-labeled ER ( Figure 3B ). 3D STED analysis showed a predominant distribution of both NS2B and 149 NS4B to the CER and more particularly to the dense ZIKV-induced crescent-shaped tubular matrix 150 in ERmoxGFP transfected U87 cells ( Figure 5A ). cache = ./cache/cord-102279-ena1usqv.txt txt = ./txt/cord-102279-ena1usqv.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102321-csdezu6y author = Booeshaghi, A. Sina title = Normalization of single-cell RNA-seq counts by log(x+1)* or log(1+x)* date = 2020-10-14 pages = extension = .txt mime = text/plain words = 1272 sentences = 84 flesch = 63 summary = log(1+x) count normalization introduces errors for lowly expressed genes The average log(1+x) expression differs considerably from log(x) when x is small An alternative approach is to use the fraction of cells with non-zero expression As is common in single-cell RNA-seq, the expression estimates of ACE2 are derived from counts that are filtered and normalized. While single-cell RNA-seq expression data has been modeled with many different distributions [4, 5] , for simplicity in illustrating our points we model this count data with a simple Poisson random variable X with parameter λ in order to demonstrate the implications of this restriction. Since f is approximately equal to this expression when f is small, this provides an interpretation of the fraction of cells with at least one copy of a low-abundance gene as an estimate of the rate parameter λ in a Poisson distribution. cache = ./cache/cord-102321-csdezu6y.txt txt = ./txt/cord-102321-csdezu6y.txt === reduce.pl bib === id = cord-102151-26lumewy author = Cox, Robert M. title = Therapeutic Targeting of Measles Virus Polymerase with ERDRP-0519 Suppresses All RNA Synthesis Activity date = 2020-09-24 pages = extension = .txt mime = text/plain words = 1797 sentences = 92 flesch = 43 summary = Results demonstrate that unlike all other mononegavirus small molecule inhibitors identified to date, ERDRP-0519 inhibits all phosphodiester bond formation in both de novo initiation of RNA synthesis at the promoter and RNA elongation by a committed polymerase complex. Photocrosslinking and resistance profiling-informed ligand docking revealed that this unprecedented mechanism of action of ERDRP-0519 is due to simultaneous engagement of the L protein polyribonucleotidyl transferase (PRNTase)-like domain and the flexible intrusion loop by the compound, pharmacologically locking the polymerase in pre-initiation conformation. Photocrosslinking-based target site 27 mapping demonstrated that this class-defining prototype inhibitor stabilizes a pre-initiation conformation 28 of the viral polymerase complex that sterically cannot accommodate template RNA. Photocrosslinking-based target site 27 mapping demonstrated that this class-defining prototype inhibitor stabilizes a pre-initiation conformation 28 of the viral polymerase complex that sterically cannot accommodate template RNA. cache = ./cache/cord-102151-26lumewy.txt txt = ./txt/cord-102151-26lumewy.txt === reduce.pl bib === id = cord-102364-t5bt2eb4 author = Yao, Dehui title = Human H-ferritin presenting RBM of spike glycoprotein as potential vaccine of SARS-CoV-2 date = 2020-06-08 pages = extension = .txt mime = text/plain words = 1852 sentences = 104 flesch = 54 summary = In an effort of utilizing human ferritin as nanoplatform for drug delivery, we engineered a fusion protein by presenting receptor-binding motif (RBM) of SARS-CoV-2 virus spike glycoprotein on the N-terminus of ferritin subunits. The designed fusion protein with a cage-like structure, similar to that of corona virus, is a potential anti-SARS-CoV-2 vaccine. We hereby show the construction, preparation, and characterization of the fusion protein RBM-HFtn. Our initial affinity study confirmed its biological activity towards ACE2 receptor which suggests its mode of action against SARS-CoV-2 could be either through vaccine therapy or blocking the cellular entry of virus as antagonist of ACE2 receptor. Antibodies targeting the spike glycoprotein of SARS-CoV and MERS-CoV, especially its receptor-binding domain (RBD), was found to efficiently neutralize virus infection [1, 2] . In this work, we engineered a human ferritin heavy chain (HFtn) by fusing and presenting the RBM of its spike glycoprotein as potential vaccine of SARS-CoV-2. cache = ./cache/cord-102364-t5bt2eb4.txt txt = ./txt/cord-102364-t5bt2eb4.txt === reduce.pl bib === === reduce.pl bib === id = cord-102530-wetqqt2i author = Brandell, Ellen E. title = The rise of disease ecology date = 2020-07-17 pages = extension = .txt mime = text/plain words = 2707 sentences = 171 flesch = 50 summary = The steady increase in topics such as climate change, and emerging infectious diseases, superspreaders indicate that disease ecology as a field of research will continue advancing our understanding of complex host-pathogen interactions and forms a critical and adaptable component of the global response to emergent health and environmental threats. In addition 164 to topics that emerged from the literature, we also generated and assessed our own topic lists based on key research areas, such as climate change, dilution effect, superspreaders, network 166 analysis, EIDs, bovine tuberculosis, infectious diseases in bats and rodents, and chytrid fungus 167 ( Fig. 4) . Using key term searches, we next explored select topic trends: climate change, emerging 293 infectious diseases (EIDs), the dilution effect, superspreaders, network analysis, pathogens in 294 rodents and bats, bovine tuberculosis, and chytrid fungus in amphibians (Fig. 4B) . cache = ./cache/cord-102530-wetqqt2i.txt txt = ./txt/cord-102530-wetqqt2i.txt === reduce.pl bib === id = cord-102350-e1vc2q4j author = Yoon, Hye-Jin title = Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation date = 2020-06-09 pages = extension = .txt mime = text/plain words = 4968 sentences = 269 flesch = 50 summary = title: Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation We report the extensive molecular dynamics simulations to gain insight into the structure and motions of NPC1 lumenal domain for cholesterol transport and disease behind the mutation (R518W). In this paper, we present extensive molecular dynamics simulations of NPC1 to understand the structural and dynamical characteristics upon R518W mutation and its effects on overall cholesterol transport efficiency in connection with possible re-location or orientation of NTD and interaction of NPC1 with NPC2. The recent molecular dynamics simulation [30] with full NPC1 when cholesterol is present in NPC1 inhibiting itraconazole binding site, [28] which is at the interface between membrane and lumenal region, shows there is non-negligible distance correlation coefficient between TMD and the rest of the domains. cache = ./cache/cord-102350-e1vc2q4j.txt txt = ./txt/cord-102350-e1vc2q4j.txt === reduce.pl bib === === reduce.pl bib === id = cord-102336-ex3zlq38 author = De Wijngaert, Brent title = Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date = 2020-04-14 pages = extension = .txt mime = text/plain words = 2266 sentences = 127 flesch = 60 summary = Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Hence, the structural basis for promoter melting, DNA scrunching, and transcription initiation remains largely unknown for the mtRNAPs. RPO41 (∆N100) and MTF1 were assembled on a pre-melted promoter (-21 to +12, 15S yeast mtDNA promoter; Fig. 1A ) to generate the yeast mitochondrial transcription preinitiation complex (y-mtPIC) (Fig. S1 ). The 3.7 Å density map of IC locates many previously uncharacterized structural elements, including the C-tail of MTF1 and the scrunched DNA ( Fig. 2B-C) , and reveals the mechanism of template alignment and RNA synthesis during initiation. During the transition, the upstream DNA from position -1 onward is locked in the MTF1 NT-groove while the template strand undergoes a large conformational switching to align with the 2-mer RNA and the incoming UTPaS at the active site ( Fig. 2C; Movie S2). cache = ./cache/cord-102336-ex3zlq38.txt txt = ./txt/cord-102336-ex3zlq38.txt === reduce.pl bib === id = cord-102270-rfhtlodc author = Azhar, Mohd. title = Rapid, field-deployable nucleobase detection and identification using FnCas9 date = 2020-04-21 pages = extension = .txt mime = text/plain words = 3971 sentences = 217 flesch = 50 summary = We then fixed the position of this mutation with respect to PAM and changed every other base in the sgRNA sequence to identify which combination led to complete loss of cleavage of a wild type substrate in an in vitro cleavage (IVC) assay with FnCas9 ( Figure 1B, Supplementary Figure 1A ). Taken together, these experiments suggest that FELUDA design can be universally used for detection of SNVs and and would not require extensive optimization or validation steps for new SNVs. To aid users for quick design and implementation of FELUDA for a target SNV, we have developed a webtool JATAYU (Junction for Analysis and Target Design for Your FELUDA assay) that incorporates the above features and generates primer sequences for amplicon and sgRNA synthesis (https:// jatayu.igib.res.in, Supplementary Figure 2 ). cache = ./cache/cord-102270-rfhtlodc.txt txt = ./txt/cord-102270-rfhtlodc.txt === reduce.pl bib === === reduce.pl bib === id = cord-102383-m5ahicqb author = Romano, Alessandra title = Energy dynamics for systemic configurations of virus-host co-evolution date = 2020-05-15 pages = extension = .txt mime = text/plain words = 3776 sentences = 190 flesch = 43 summary = A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. cache = ./cache/cord-102383-m5ahicqb.txt txt = ./txt/cord-102383-m5ahicqb.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102412-cnlvyey4 author = Tekman, Mehmet title = A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework date = 2020-08-28 pages = extension = .txt mime = text/plain words = 6419 sentences = 300 flesch = 53 summary = Results Here we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The analysis of scRNA-seq within Galaxy was a two-pronged e ort concentrated on bringing high quality single-cell tools into Galaxy, and providing the necessary work ows and training to accompany them. The training pictographically guides users through the concepts of extracting cell barcodes from the protocol, explains the signi cance of UMIs in the process of read deduplication with illustrative examples, and instructs the user in the process of performing further quality controls on their data during the post-mapping process via RNA STAR and other tools that are native to Galaxy. A Galaxy-based training resource for single-cell RNA-sequencing quality control and analyses cache = ./cache/cord-102412-cnlvyey4.txt txt = ./txt/cord-102412-cnlvyey4.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102729-b1q7gbd6 author = Mickael, Alexandra title = Asip (Agouti-signaling protein) aggression gene regulate auditory processing genes in mice date = 2020-06-12 pages = extension = .txt mime = text/plain words = 4430 sentences = 281 flesch = 48 summary = ASIP (nonagouti) gene plays a vital role in regulating the melanocortin GPCRs family function, and it is responsible for regulating aggression in mice. We found that ASIP KO in mice upregulates several genes controlling auditory function, including Phox2b, Mpk13, Fat2, Neurod2, Slc18a3, Gon4l Gbx2, Slc6a3(Dat1) Aldh1a7 Tyrp1 and Lbx1. In order to confirm that our mice model study would be representative of aggression hearing link, we conducted an evolutionary study that revealed that ASIP is negatively selected between mice and humans. When we analyzed RNA-seq for Asip ko mouse model we found that several genes controlling hearing were upregulated in the KO samples. We found these results reflected in the molecular pathway of melanocortin receptors 1 and 4, where their knocking out their negative agonist; Asip resulted in upregulating various hearing associated genes such as Fat2 among others. cache = ./cache/cord-102729-b1q7gbd6.txt txt = ./txt/cord-102729-b1q7gbd6.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102551-8igfuaw2 author = Boonyaratanakornkit, Jim title = Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection date = 2020-10-30 pages = extension = .txt mime = text/plain words = 8067 sentences = 462 flesch = 53 summary = HPIV3, like respiratory syncytial virus (RSV), infects early in life and frequently causes severe bronchiolitis and pneumonia in infants under six months of age who are unable to mount a robust antibody response 2,3 . HPIV3 F was recently stabilized in the preF conformation and induced higher serum neutralizing titers than the HPIV3 postF To focus upon B cells producing neutralizing antibodies, we modified our assay to sort individual B cells onto irradiated 3T3 feeder cells expressing CD40L, IL-2, and IL-21 to allow for higher throughput screening of culture supernatants for neutralization prior to antibody cloning, as described 27 . Using this approach, we found that 14% of IgD -HPIV3 preF-binding B cells sorted from tonsils produced HPIV3 neutralizing antibodies, as compared to 5% from the spleen and 2% from peripheral blood (Fig. 3b) . cache = ./cache/cord-102551-8igfuaw2.txt txt = ./txt/cord-102551-8igfuaw2.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102458-7sssm3zk author = Milanez-Almeida, Pedro title = Blood gene expression-based prediction of lethality after respiratory infection by influenza A virus in mice date = 2020-10-27 pages = extension = .txt mime = text/plain words = 4637 sentences = 172 flesch = 42 summary = During training (i.e., model selection via cross-validation), the algorithm learned that 11 genes had expression values in blood that could be linearly combined to generate a scoring system of infected animals as a function of the day of death ( In both the multinomial and the lethal Cox models, high levels of expression of genes associated with monocytes and neutrophils, together with low levels of transcripts associated with lymphocytes, indicated high risk of death (Fig. S3 ), consistent with previously described analyses of the immune response to IAV infection (10, 12, 13) and also recent data from COVID-19 patients (29). While the lack of accuracy later in the course of infection (i.e., days seven and eight) was likely due to the fact that the model was trained for early detection of lethality, before adaptive immune cells fully developed and reached the circulation, these data suggest that PAMPs and DAMPs eventually reach different levels in the lungs of different mice, impacting their blood cell composition and lethal score, which can be used for prediction of lethality of individual animals even in the challenging scenario of experimental infection with an 1 LD50 IAV dose. cache = ./cache/cord-102458-7sssm3zk.txt txt = ./txt/cord-102458-7sssm3zk.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102704-wfuzk2dp author = Meza, Diana K. title = Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities date = 2020-04-30 pages = extension = .txt mime = text/plain words = 3183 sentences = 192 flesch = 43 summary = Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained. The binomial and log-normal models fit to 193 this data subset included only the fixed effect of the virus-infected N2A cell counts, but the random 194 effects were identical to those explained above (i.e. test date and field). A final distinction is that 316 instead of scoring microscope field or wells as virus positive or negative, the pmRFFIT predicts 317 serological status and RVNA titer from infected cell counts in a single serum dilution using statistical 318 cache = ./cache/cord-102704-wfuzk2dp.txt txt = ./txt/cord-102704-wfuzk2dp.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102976-cic1gxrk author = Patel, Roosheel S. title = Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells date = 2020-05-07 pages = extension = .txt mime = text/plain words = 7155 sentences = 378 flesch = 45 summary = Single cell RNA-Sequencing (scRNA-Seq) offers an alternative to flow cytometry as it defines different cell types (and their functional states) by gene expression patterns rather than surface marker expression. To characterize equine PBMC at high resolution and establish a corresponding peripheral blood immune cell atlas, we independently analyzed scRNA-Seq data for the constituent clusters of each major cell group, except Basophils due to the low number of cells. Additional genes with significantly elevated expression levels in cluster 28 include NR4A1 (transcription factor necessary for differentiation of non-classical monocytes in mice) (23) , CX3CR1 (chemokine receptor characteristic of nonclassical monocytes in humans and mice) (24, 25) , and HES4 (target of NOTCH signaling implicated in non-classical monocyte generation) (26) (Fig. 2E ). To further support our cell type annotations and assess potential differences in monocyte/DC subsets between horses and humans, we performed cross-species hierarchical clustering with a human PBMC public reference scRNA-Seq data set ( Fig. S2A-B, Fig. 2G ). cache = ./cache/cord-102976-cic1gxrk.txt txt = ./txt/cord-102976-cic1gxrk.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-102968-mhawyect author = Desirò, Daniel title = SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structural RNAs date = 2018-09-23 pages = extension = .txt mime = text/plain words = 4044 sentences = 233 flesch = 58 summary = Results Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate destructive and compensatory mutants of two interacting single-stranded RNAs. This will facilitate a fast and accurate assessment of key regions, possibly involved in functional long-range RNA-RNA interactions and finally help virologists to design appropriate experiments. In this study, we present a tool called SilentMutations (SIM) that effectively simulates synonymous (silent) compensatory mutations in two single-stranded viral RNAs and is therefore appropriate for the in vitro assessment of predicted LRIs. Here, we present a command-line tool, called SilentMutations (SIM), that can simulate synonymous structure-destroying and structurepreserving mutation pairs within coding regions for long-range RNA-RNA interaction experiments. Figure 1 : Overall workflow of the SilentMutations tool, exemplary shown for two sequences from a negative single-stranded RNA virus genome (ssRNA-) (a) The first step will extract the defined range in each sequence and possibly increase the range to preserve codons in the given reading frame. cache = ./cache/cord-102968-mhawyect.txt txt = ./txt/cord-102968-mhawyect.txt === reduce.pl bib === id = cord-102763-tc1z0nm9 author = Zhang, Yuan title = IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability date = 2020-05-21 pages = extension = .txt mime = text/plain words = 1764 sentences = 104 flesch = 53 summary = Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. We developed a highly thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The newborn mice receiving passive transfer of IgY achieved complete protection against a lethal dose of virus challenge indicating that the anti-EBOV IgY provides a promising countermeasure to solve the current clinical application problems of Ebola antibody-based treatments in Africa. To obtain high titer EBOV NAbs, 5-month-old laying hens were vaccinated with five different 124 immunogens, including 10 3 or 10 4 TCID 50 VSVΔ G/EBOVGP, 100 μ g rEBOVGP, 100 μ g 125 pCAGGS/EBOVGP, 10 μg EBOV-VLP, and 10 11 virus particles (vp) Ad5/EBOVGP (Fig 2a) . Protective 546 monotherapy against lethal Ebola virus infection by a potently neutralizing antibody Protective 546 monotherapy against lethal Ebola virus infection by a potently neutralizing antibody cache = ./cache/cord-102763-tc1z0nm9.txt txt = ./txt/cord-102763-tc1z0nm9.txt === reduce.pl bib === id = cord-102749-tgka0pl0 author = Tovo, Anna title = Taxonomic classification method for metagenomics based on core protein families with Core-Kaiju date = 2020-05-01 pages = extension = .txt mime = text/plain words = 7844 sentences = 352 flesch = 47 summary = In this study, we first apply and compare different bioinformatics methods based on 16S ribosomal RNA gene and whole genome shotgun sequencing for taxonomic classification to three small mock communities of bacteria, of which the compositions are known. In particular, we propose an updated version of Kaiju, which combines the power of shotgun metagenomics data with a more focused marker gene classification method, similar to 16S rRNA, but based on core protein domain families (40, 41, 42, 43) from the PFAM database (44) . As shown in (27) , where different amplicon sequencing methods are tested on both simulated and real data and the results are compared to those obtained with metagenomic pipelines, the whole genome approach resulted to outperform the previous ones in terms of both number of identified strains, taxonomic and functional resolution and reliability on estimates of microbial relative abundance distribution in samples. cache = ./cache/cord-102749-tgka0pl0.txt txt = ./txt/cord-102749-tgka0pl0.txt === reduce.pl bib === id = cord-102892-nt1zoktv author = Sweeney, Blake A. title = R2DT: computational framework for template-based RNA secondary structure visualisation across non-coding RNA types date = 2020-09-11 pages = extension = .txt mime = text/plain words = 3366 sentences = 188 flesch = 54 summary = Consensus tRNA primary 213 sequence with 2D structure for each isotype of each taxonomic domain was generated based 214 on the tRNA alignments used for building the isotype-specific covariance models in tRNAscan-215 SE 2.0 16 . 270 R2DT templates model the conserved core of most structured RNAs We classified each nucleotide in the resulting diagrams according to whether it matched a 282 template and found that 90.6% of nucleotides were displayed using the nucleotide locations 283 encoded in the templates, while 6.0% of nucleotides represented insertions compared to the 284 templates, and 3.4% of nucleotides matched the templates but required automatic repositioning 285 by the Traveler software (Table 2) . In addition, R2DT will benefit from the ongoing development Isotype-specific consensus tRNA sequences and 2D structures were generated using R-scape 52 389 from the alignments that were used to train and build the corresponding covariance models in 390 tRNAscan-SE 16 . cache = ./cache/cord-102892-nt1zoktv.txt txt = ./txt/cord-102892-nt1zoktv.txt === reduce.pl bib === id = cord-102905-rlee32x7 author = Leis, Jonathan title = Ilaprazole and other novel prazole-based compounds that bind Tsg101 inhibit viral budding of HSV-1/2 and HIV from cells date = 2020-05-04 pages = extension = .txt mime = text/plain words = 5755 sentences = 297 flesch = 51 summary = In this report we show that tenatoprazole and a related prazole drug, ilaprazole, effectively block infectious Herpes Simplex Virus (HSV)-1/2 release from Vero cells in culture. Our results indicate that prazole-based compounds may represent a class of drugs with potential to be broad-spectrum antiviral agents against multiple enveloped viruses, by interrupting cellular Tsg101 interaction with maturing virus, thus blocking the budding process that releases particles from the cell. Tenatoprazole and esomeprazole were shown to quantitatively inhibit the release of infectious HIV-1 from 293T cells in culture, and it was suggested that these effects may be mediated via changes in viral interaction with Tsg101, a key component of the cellular ESCRT complex (5, 33) . Given multiple reports suggesting that herpes viruses also use cellular ESCRT proteins in their replication process (20) (21) (22) (23) we tested if the Tsg101-binding prazole drugs, which blocked budding of HIV-1, would also block the release of herpes viruses from cells. cache = ./cache/cord-102905-rlee32x7.txt txt = ./txt/cord-102905-rlee32x7.txt === reduce.pl bib === id = cord-102918-bkyk7or9 author = Burns, C. Sean title = Methodological Issues with Search in MEDLINE: A Longitudinal Query Analysis date = 2020-05-22 pages = extension = .txt mime = text/plain words = 1414 sentences = 89 flesch = 51 summary = This study compares the results of data collected from a longitudinal query analysis of the MEDLINE database hosted on multiple platforms that include PubMed, EBSCOHost, Ovid, ProQuest, and Web of Science in order to identify variations among the search results on the platforms after controlling for search query syntax. The variation is due to trends in scholarly publication that include publishing online first versus publishing in journal issues, which leads to metadata differences in the bibliographic record; to differences in the level of specificity among search fields provided by the platforms; to database integrity issues that lead to large fluctuations in monthly search results based on the same query; and to database currency issues that arise due to when each platform updates its MEDLINE file. Specific bibliographic databases, like PubMed and MEDLINE, are used to inform clinical decision-making, create systematic reviews, and construct knowledge bases for clinical decision support systems. Comparing the coverage, recall, and precision of searches for 120 systematic reviews in Embase, MEDLINE, and Google Scholar: a prospective study cache = ./cache/cord-102918-bkyk7or9.txt txt = ./txt/cord-102918-bkyk7or9.txt === reduce.pl bib === id = cord-102920-z5q3wo7v author = Sang, Eric R. title = Integrate Structural Analysis, Isoform Diversity, and Interferon-Inductive Propensity of ACE2 to Refine SARS-CoV2 Susceptibility Prediction in Vertebrates date = 2020-06-28 pages = extension = .txt mime = text/plain words = 6437 sentences = 316 flesch = 44 summary = Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad SARS-CoV2 susceptibility in wild and particularly domestic animals. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Along with showing a broad susceptibility potential across mammalian species based on structural analysis [26] [27] [28] , our results further reveal that domestic animals including dogs, pigs, cattle and goats may evolve previously unexamined immunogenetic diversity to restrict SARS-CoV2 infections. In addition to structural analysis of simulated S-RBD-ACE2 interaction, we propose that several immunogenetic factors, including the evolution of S-binding-void ACE2 isoforms in some domestic animals, the species-specific IFN system, and epigenetic regulation of IFN-stimulated property of host ACE2 genes, contribute to the viral susceptibility and the development of COVID-19-like symptoms in certain animal species [15, 38, 39, 49] . cache = ./cache/cord-102920-z5q3wo7v.txt txt = ./txt/cord-102920-z5q3wo7v.txt === reduce.pl bib === id = cord-102967-dx0tg077 author = Mahajan, Lakshmi S. title = Mapping RNA dependent RNA polymerase activity and immune gene expression using PRO-seq date = 2020-06-16 pages = extension = .txt mime = text/plain words = 2853 sentences = 163 flesch = 57 summary = Coupled to PRO-seq in human blood samples, we propose to use PRO-seq as a single package method to detect (+)ssRNA virus RdRp activity and its interaction with host immune response through transcriptome-wide profiling of leukocyte gene expressions at once. This is different from Drosophila RNA Polymerase II, which appears to have comparable substrate specificity for all 4 biotin-NTPs. The ORF-proximal accumulation coincides with quadruplet rich regions of the template-strand of the DAV genome ( Figure 1D ). From this data, we did not detect significant PRO-seq sequences from (+)ssRNA viral genomes, indicating that none of the individuals had direct viral infections in the blood immune cells. Our PRO-seq data show expression levels of immune-response related genes from human peripheral blood leukocytes. PRO-seq density on DAV genome and base-quadruplet counts.The read count is indicated along the left side of each graph. Base-pair-resolution genome-wide mapping of active RNA polymerases using precision nuclear run-on (PRO-seq) cache = ./cache/cord-102967-dx0tg077.txt txt = ./txt/cord-102967-dx0tg077.txt === reduce.pl bib === id = cord-103015-3dxwbmd2 author = Shengjuler, Djoshkun title = The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain date = 2017-08-04 pages = extension = .txt mime = text/plain words = 7069 sentences = 411 flesch = 63 summary = Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using NMR spectroscopy. 93 Validation of PIP-binding sites by NMR 94 In order to test the validity of our docking observations, we titrated 15 N-labeled 3C protein 95 with soluble dibutyl-PI4P to observe potential NMR chemical shift perturbations (CSPs), which 96 would indicate chemical environment changes in the presence of PI4P (Figure 2) . Out of the three 97 basic residues of the major cluster that were predicted to interact with the PI4P, R13 showed the 98 largest CSP (Figure 2A ). Titration of PI4P into a solution containing 3C caused CSPs that were consistent 249 with the major PI4P-binding site observed computationally (Figure 2A) . cache = ./cache/cord-103015-3dxwbmd2.txt txt = ./txt/cord-103015-3dxwbmd2.txt === reduce.pl bib === id = cord-102908-sr7j8z9c author = Mersmann, Sophia F. title = Learning to count: determining the stoichiometry of bio-molecular complexes using fluorescence microscopy and statistical modelling date = 2020-07-24 pages = extension = .txt mime = text/plain words = 5244 sentences = 260 flesch = 42 summary = We used differential binary labelling and statistical modelling to extract estimates of stoichiometry, our strategy is outlined in Figure 1 ; note that this approach can be generalised to apply to many other multi-component systems (i.e. how many protein x are found in assembly y?). As described above, our experimental design utilizes antibody labelled with spectrally distinct dyes allowing binary scoring of individual virus particles as positive if they interact with at least one Ab B molecule ( Figure 1 ). We have demonstrated quantitative analysis of 9C12 interaction with individual Adv particles ( Figure 3) ; we have confirmed that differential labelling of antibody does not bias binding ( Figure 4A & B) ; and that we could detect single molecules of 9C12 Biotin allowing discrimination of positive and negative AdV-9C12 complexes ( Figure 4C & D). However, using stoichiometric estimates to calibrate fluorescent data revealed population heterogeneity with a small proportion of virus particles binding ∼200 antibody molecules. cache = ./cache/cord-102908-sr7j8z9c.txt txt = ./txt/cord-102908-sr7j8z9c.txt === reduce.pl bib === id = cord-102958-q8jamg07 author = Hahka, Taija M. title = Resiniferatoxin (RTX) ameliorates acute respiratory distress syndrome (ARDS) in a rodent model of lung injury date = 2020-09-14 pages = extension = .txt mime = text/plain words = 3737 sentences = 219 flesch = 45 summary = We ablated cardiopulmonary spinal afferents through either epidural T1-T4 dorsal root ganglia (DRG) application or intra-stellate ganglia delivery of a selective afferent neurotoxin, resiniferatoxin (RTX) in rats 3 days post bleomycin-induced lung injury. Our data showed that both epidural and intra-stellate ganglia injection of RTX significantly reduced plasma extravasation and reduced the level of lung pro-inflammatory cytokines providing proof of principle that cardiopulmonary spinal afferents are involved in lung pathology post ALI. Therefore, in the current study we hypothesized that ablation of lung afferent innervation (thoracic spinal) by application of an ultrapotent, selective afferent neurotoxin, resiniferatoxin (RTX) will modify the course of the pathology including lung edema and local pulmonary inflammation associated with progressive ALI. 2 1 Our data suggest that pulmonary spinal afferent ablation by intra-stellate injection of RTX reduces plasma extravasation and local pulmonary inflammation post bleomycininduced lung injury which results in improved blood gas exchange. cache = ./cache/cord-102958-q8jamg07.txt txt = ./txt/cord-102958-q8jamg07.txt === reduce.pl bib === id = cord-102886-oo7q05ml author = Gomes, Fabio M. title = “Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes” date = 2020-09-10 pages = extension = .txt mime = text/plain words = 1963 sentences = 116 flesch = 45 summary = title: "Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes" Immune priming in Anopheles gambiae mosquitoes following infection with Plasmodium parasites is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4 bound to Evokin, a lipid carrier. We provide direct evidence that modifications mediated by the histone acetyltransferase AgTip60 (AGAP01539) are essential for sustained oenocyte proliferation, HDF synthesis and immune priming. We propose that oenocytes function as a population of "memory" cells that continuously release lipoxin to orchestrate and maintain a broad, systemic and long-lasting state of enhanced immune surveillance. We recently showed that two heme peroxidases, HPX7 and HPX8, are necessary for midgut PGE 2 synthesis and are essential to establish immune priming in response to Plasmodium infection (8) . These cells express high levels of DBLOX and their proliferation is essential for HDF synthesis and to maintain the priming response. cache = ./cache/cord-102886-oo7q05ml.txt txt = ./txt/cord-102886-oo7q05ml.txt === reduce.pl bib === id = cord-102977-yci9kq6x author = Liu, Haiming title = GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia date = 2019-12-06 pages = extension = .txt mime = text/plain words = 4891 sentences = 291 flesch = 59 summary = This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma (LLC)-induced cachexia model and those mediating the effects of ghrelin in Ghsr+/+ and Ghsr−/− mice. GHSR-1a is not expressed in adipocytes (Sun, Garcia et 243 al., 2007) but is present in macrophages (Ma, Lin et al., 2013) and our findings are consistent with a 244 previous report showing that old, non-tumor-bearing Ghsr -/mice have reduced macrophage 245 infiltration, a shift on macrophage differentiation towards a more anti-inflammatory phenotype, and 246 decreased inflammation in adipose tissue (Lin, Lee et al., 2016) . In this study, we did 278 not see a significant effect of ghrelin on preventing LLC-induced fat browning, BAT thermogenesis, 279 increased REE or decreased physical activity in the setting of CACS despite the fact that ghrelin 280 prevented fat and weight loss and anorexia. cache = ./cache/cord-102977-yci9kq6x.txt txt = ./txt/cord-102977-yci9kq6x.txt === reduce.pl bib === id = cord-102835-71ome9h8 author = Levinson, Maxwell Adam title = FAIRSCAPE: A Framework for FAIR and Reproducible Biomedical Analytics date = 2020-08-15 pages = extension = .txt mime = text/plain words = 4772 sentences = 288 flesch = 51 summary = All results are annotated with FAIR metadata using the evidence graph model for access, validation, reproducibility, and re-use of archived data and software. We set out to construct a provenance-aware computational data lake, as described above, by significantly extending and refactoring the identifier and metadata services framework we and our colleagues developed in the NIH Data Commons Pilot Project Consortium (Timothy Clark et al. We extended and re-engineered this framework over time to track and visualize computations and their evidence, to manage the computational objects (such as data and software) as well as their metadata, to analyze very large datasets with horizontal scale-out, to support neuroimaging workflows, and to make it generally more easy for scientists and computational analysts to use, by providing Binder and Notebook services (Jupyter et al. It supports transparent disclosure of the Evidence Graphs of computed results, with access to the persistent identifiers of the cited data or software, and to their stored metadata. cache = ./cache/cord-102835-71ome9h8.txt txt = ./txt/cord-102835-71ome9h8.txt === reduce.pl bib === id = cord-102931-vxkbctiz author = Mao, Kai title = Induction of RNA interference by C. elegans mitochondrial dysfunction via the DRH-1/RIG-I homologue RNA helicase and the EOL-1/RNA decapping enzyme date = 2020-06-06 pages = extension = .txt mime = text/plain words = 8680 sentences = 503 flesch = 49 summary = Here, we report that mitochondrial dysfunction in Caenorhabditis elegans activates RNAi-directed silencing via induction of a pathway homologous to the mammalian RIG-I helicase viral response pathway. elegans compared to most animals, and surprisingly, loss of function mutations in some of those genes cause an increase in the response to siRNAs: mutations in the RdRp RRF-3, the specialized Argonaute ERGO-1, the RNA helicase ERI-6/7, or the exoribonuclease ERI-1 enhance silencing by siRNAs (Fischer et al., 2008; Kennedy et al., 2004) . We find that reduction of function mutations in a wide range of mitochondrial components robustly enhanced RNA interference-mediated silencing of endogenous genes as well as a variety of reporters of RNAi. These antiviral responses to mitochondrial dysfunction are homologous to the RIG-I-based mitochondrial response in mammals because they depend on the RIG-I homologue, the DRH-1 RNA helicase. Our analysis of the eol-1 and drh-1 pathway from mitochondrial dysfunction to enhanced RNA interference and antiviral activity is a key output from mitochondria for anti-aging. cache = ./cache/cord-102931-vxkbctiz.txt txt = ./txt/cord-102931-vxkbctiz.txt === reduce.pl bib === id = cord-102935-cx3elpb8 author = Hassani-Pak, Keywan title = KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species date = 2020-04-24 pages = extension = .txt mime = text/plain words = 2172 sentences = 119 flesch = 60 summary = Here we report the main design principles behind KnetMiner and provide use cases for mining public datasets to identify unknown links between traits such grain colour and pre-harvest sprouting in Triticum aestivum, as well as, an evidence-based approach to identify candidate genes under an Arabidopsis thaliana petal size QTL. KnetMiner is the first open-source gene discovery platform that can leverage genome-scale knowledge graphs, generate evidence-based biological networks and be deployed for any species with a sequenced genome. Even when 38 the task of gathering information is complete, it is demanding to assemble a coherent view of how 39 each piece of evidence might come together to "tell a story" about the biology that can explain how 40 multiple genes might be implicated in a complex trait or disease. cache = ./cache/cord-102935-cx3elpb8.txt txt = ./txt/cord-102935-cx3elpb8.txt === reduce.pl bib === id = cord-102570-lpwwlrqm author = Fenn, Gareth D. title = Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase) date = 2020-08-18 pages = extension = .txt mime = text/plain words = 3428 sentences = 205 flesch = 63 summary = In the human-IMPase-complex ebselen, in a ring opened conformation, is covalently attached to Cys141, a residue located away from the active site. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins. Synopsis Here we present a 1.47Å crystal structure of human inositol monophosphatase (IMPase) bound to the inhibitor ebselen (PDB entry 6ZK0). In this paper, we present a 1.47Å structure of ebselen covalently bound to cysteine residue 141 of human IMPase (PDB entry 6ZK0). Each monomer of IMPase in this structure has a single ebselen molecule bound to Cys141 (PDB entry 6ZK0). The IMPase crystal structure that is presented (PDB entry 6ZK0) has ebselen covalently attached to Cys141, however it is not clear to what extent this binding brings about ebselen's inhibitory effects on IMPase. cache = ./cache/cord-102570-lpwwlrqm.txt txt = ./txt/cord-102570-lpwwlrqm.txt === reduce.pl bib === id = cord-102964-zh737cjk author = Ferraro, Francesco title = Modulation of endothelial organelle size as an antithrombotic strategy date = 2020-05-17 pages = extension = .txt mime = text/plain words = 5532 sentences = 357 flesch = 43 summary = Out of 1280 human licensed drugs we found 58 compounds fitting our criteria, with a variety of mechanisms of action consistent suggesting a number of pathways that influence biogenesis of WPBs. A quantitative high-throughput microscopy-based workflow, dubbed highthroughput morphometry (HTM), allows rapid quantification of the size of tens to hundreds of thousands of WPBs within thousands of endothelial cells (Ferraro et al., 2014) . We have previously shown that treatment of endothelial cells with two statins, simvastatin and fluvastatin, induces WPB size shortening, resulting in reduced adhesive properties of the VWF released by activated endothelial cells (HUVEC), measured by the reduced size of platelet-decorated VWF strings and by the recruitment of VWF from a flowing plasma pool (Ferraro et al., 2016) . Further to the potential toxicity associated with administration of drugs at high concentrations, we note that in vitro combination of WPB-size reducing treatments, acting through different mechanisms, can display synergy in the abatement of plasma VWF recruitment to the endothelial surface (Supplemental Figure 1) . cache = ./cache/cord-102964-zh737cjk.txt txt = ./txt/cord-102964-zh737cjk.txt === reduce.pl bib === id = cord-103077-sh4w2mye author = Lu, Shuai title = Leveraging Sequential and Spatial Neighbors Information by Using CNNs Linked With GCNs for Paratope Prediction date = 2020-10-16 pages = extension = .txt mime = text/plain words = 3140 sentences = 194 flesch = 55 summary = In this article, we propose a method to identify which amino acid residues of an antibody directly interact with its associated antigen based on the features from sequence and structure. Our algorithm uses convolution neural networks (CNNs) linked with graph convolution networks (GCNs) to make use of information from both sequential and spatial neighbors to understand more about the local environment of the target amino acid residue. According to the type of selecting neighbors of target residue for representing and predicting, the machine learning-based methods can be divided into two categories, leveraging sequential neighbors or spatial neighbors. And the stateof-art method [19] represented an antibody as a graph where each amino acid residue was a node and K nearest spatial neighbors were used in the convolution operator. In this work, we utilize the sequential and spatial neighbors of the target antibody residue by using Convolutional Neural Networks (CNNs) linked with Graph Neural Networks (GCNs) for paratope prediction. cache = ./cache/cord-103077-sh4w2mye.txt txt = ./txt/cord-103077-sh4w2mye.txt === reduce.pl bib === id = cord-103081-k7ev5qkn author = Janosevic, Danielle title = The orchestrated cellular and molecular responses of the kidney to endotoxin define the sepsis timeline date = 2020-05-30 pages = extension = .txt mime = text/plain words = 4505 sentences = 310 flesch = 57 summary = Note that the expression of cluster-defining markers varied significantly during the injury and 63 recovery phases of sepsis ( Fig. S1b; Supplementary Table 1 ). One of the subclusters showed 112 increased expression of alternatively activated macrophages (M2) markers such as Arg1 113 (Arginase 1) and Mrc1 (Cd206) 27 at later time points (36 hours, Supplementary Fig. 4b) . Such 181 communication patterns among these four cell types may also explain macrophage clustering 182 around S1 tubules at later time points in sepsis as we previously reported 13 . To this end, we selected the differentially expressed genes from all cells combined (pseudo 203 bulk) for each time point across the mouse sepsis timeline (Supplementary Table 4) . Our data 215 cover nearly all renal cell types and are time-anchored, thus providing a detailed and precise 216 view of the evolution of sepsis in the kidney at the cellular and molecular level. cache = ./cache/cord-103081-k7ev5qkn.txt txt = ./txt/cord-103081-k7ev5qkn.txt === reduce.pl bib === id = cord-103135-nly9vojr author = Fletcher, Nicola F. title = A novel antiviral formulation inhibits a range of enveloped viruses date = 2020-03-30 pages = extension = .txt mime = text/plain words = 6468 sentences = 329 flesch = 47 summary = ViroSAL had no effect on the infectivity of a non-enveloped virus, norovirus, which is in agreement with previous studies demonstrating that free fatty acids are ineffective against nonenveloped viruses (Thormar et al., 1987 , Kohn et al., 1980 . In this study, ViroSAL at the indicated concentrations was mixed with an equal volume of viral inoculum (MeV:original TCID50 = 4.48 7 /mL, HSV-1: 100 PFU/mL, EBV: MOI=10, Zika: MOI=10, Orf: 4 PFU/mL) or pseudoviruses bearing VSV, Ebola, Lassa or SARS-CoV-1 envelope glycoproteins, and incubated at room temperature for 2 minutes. Virus/ViroSAL or control treated virus was inoculated onto appropriate target cells and incubated for 48h at 37°C, then fixed and infection enumerated, or, for pseudovirus assays, lysed and luciferase activity quantified as previously described (Fletcher et al., 2015) . Milk-based free fatty acids, as well as fatty acid emulsions, have been shown to inhibit infection of Vero cells with VSV and HSV-1, with no antiviral effect on poliovirus, a non-enveloped virus (Thormar et al., 1987) . cache = ./cache/cord-103135-nly9vojr.txt txt = ./txt/cord-103135-nly9vojr.txt === reduce.pl bib === id = cord-103071-6cgih8o9 author = Mead, Benjamin E. title = High-throughput organoid screening enables engineering of intestinal epithelial composition date = 2020-04-28 pages = extension = .txt mime = text/plain words = 12408 sentences = 655 flesch = 50 summary = Strikingly, in our screen we identify inhibitors of the nuclear exporter Xpo1 modulate stem cell fate commitment by inducing a pan-epithelial stress response combined with an interruption of mitogen signaling in cycling intestinal progenitors, thereby significantly increasing the abundance of Paneth cells independent of known WNT and Notch differentiation cues. Administration of KPT-330 below 160 nM for 6 days (NB higher concentrations proved toxic in primary screening) showed LYZ secretion increasing in a dose-dependent manner, with 160 nM of KPT-330 as the most effective dose among tested concentrations KPT-330 is a selective inhibitor of nuclear export (SINE); these molecules act by suppressing the Xpo1-regulated nuclear export of multiple proteins and mRNAs from the nucleus to the cytoplasm -including genes involved in stem cell maintenance and differentiation as well as inflammatory stress response (Sendino et al., 2018) . cache = ./cache/cord-103071-6cgih8o9.txt txt = ./txt/cord-103071-6cgih8o9.txt === reduce.pl bib === id = cord-102811-jlr4vb4u author = Baumeister, Sebastian E title = Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study date = 2019-10-29 pages = extension = .txt mime = text/plain words = 2194 sentences = 111 flesch = 38 summary = Several meta-analyses of observational studies suggested a protective effect of physical activity for cognitive decline and risk of dementia and AD [3] [4] [5] [6] [7] [8] [9] [10] . Mendelian randomization (MR) is a method that uses genetic variants as instrumental variables to uncover causal relationships in the presence of observational study bias such as unobserved confounding and reverse causation [15] . We selected eight SNPs associated with accelerometer-based physical activity (mean acceleration in milli-gravities) at a genome-wide significance level (P < 5 x 10 -8 ), using a PLINKclumping algorithm (r² threshold = 0.001 and window size = 10mB), from a genome-wide study of 91,084 UK Biobank participants [16] (Supplementary Table 1 ). Summary data for the association of SNPs for accelerometer-based physical activity with AD were obtained from a GWAS of 21,982 clinically-confirmed AD cases and 41,944 cognitively normal controls [17] . Physical activity can improve cognition in patients with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials cache = ./cache/cord-102811-jlr4vb4u.txt txt = ./txt/cord-102811-jlr4vb4u.txt === reduce.pl bib === id = cord-102916-t2lcd300 author = Cai, Guoshuai title = SCANNER: A Web Resource for Annotation, Visualization and Sharing of Single Cell RNA-seq Data date = 2020-07-14 pages = extension = .txt mime = text/plain words = 1487 sentences = 81 flesch = 47 summary = title: SCANNER: A Web Resource for Annotation, Visualization and Sharing of Single Cell RNA-seq Data Also, it is equipped with multiple data interfaces for easy data sharing and currently provide a database for studying the smoking effect on single cell gene expression in lung. Contact GCAI@mailbox.sc.edu or XIAOF@mailbox.sc.ecu Key Points SCANNER provides a new web server resource for promoting scRNA-seq data analysis SCANNER enables comprehensive and dynamic analysis and visualization, novel functional annotation and activeness inference, online databases and easy data sharing. In this study, we developed the Single Cell Transcriptomics Annotated Viewer (SCANNER), as a public web resource for scRNA-seq data management, analysis and interpretation in a comprehensive, flexible and collaborative manner. Exploring our database of smoking lung, we found that the gene of the SARS-CoV-2 receptor, ACE2, is mainly expressed in pneumocytes, secretory cells and ciliated cells (Fig. S6) , which is consistent with the recent study of Ziegler et al. cache = ./cache/cord-102916-t2lcd300.txt txt = ./txt/cord-102916-t2lcd300.txt === reduce.pl bib === id = cord-103055-071a5b0x author = Rathbun, LI title = PLK1- and PLK4-mediated asymmetric mitotic centrosome size and positioning in the early zebrafish embryo date = 2020-04-14 pages = extension = .txt mime = text/plain words = 3126 sentences = 156 flesch = 49 summary = We propose a model in which uniquely large centrosomes direct spindle placement within the disproportionately large zebrafish embryo cells to orchestrate cell divisions during early embryogenesis. This is clearly visualized through the use of a fluorescent microtubule transgenic zebrafish line (EMTB-3xGFP) [7] , where the 16-cell stage embryo contains mitotic spindles oriented perpendicular to the previous division at the 8 In early development, rapid rounds of division result in a stark decrease in cell size during the cleavage stage [8] . Strikingly, mitotic centrosomes in zebrafish embryos were extremely large with g-tubulin organized into a wheel-like structure (246.44±11.93μm 2 at 8-cell stage, Figure 1E ), compared to g-tubulin in C. elegans and zebrafish embryos, cell length and mitotic centrosome area decreased by 30-40% over time. In order to determine the importance of PLK1/4-dependent asymmetric mitotic centrosome size placement in early zebrafish divisions, we raised embryos after injection of 1% DMSO, 1μM BI2536, or 1μM centrinone ( Figure 4F ). cache = ./cache/cord-103055-071a5b0x.txt txt = ./txt/cord-103055-071a5b0x.txt === reduce.pl bib === id = cord-103085-vf4qyvft author = Seitz, Christian title = Multiscale simulations examining glycan shield effects on drug binding to influenza neuraminidase date = 2020-11-02 pages = extension = .txt mime = text/plain words = 9735 sentences = 512 flesch = 50 summary = Using Brownian dynamics simulations, we observe a twoto eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. We have utilized BD to estimate the rates of binding of small molecules to the primary (i.e. active/catalytic) and secondary (i.e. hemadsorption) binding sites of influenza neuraminidase in glycosylated and unglycosylated states. The protein-ligand atom pairs were taken from crystal structures of ligands in the primary and secondary sites of neuraminidase for each monomer, and simulations were run for the full tetramer. Keeping in mind the primary and secondary binding sites are located just beneath the glycans (Figure 1) , the size and flexibility of the glycans here shows that they have the capability to "shield" the binding sites from ligand association. (A) The glycan structures from the MD simulations show a moderate association rate inhibition to the primary binding site irrespective of ligand chosen. cache = ./cache/cord-103085-vf4qyvft.txt txt = ./txt/cord-103085-vf4qyvft.txt === reduce.pl bib === id = cord-103105-iqjksoim author = Marinaik, Chandranaik B. title = Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants date = 2020-07-10 pages = extension = .txt mime = text/plain words = 7343 sentences = 406 flesch = 55 summary = An acrylic acid-based adjuvant (ADJ), in combination with TLR agonists glucopyranosyl lipid adjuvant (GLA) or CpG promoted mucosal imprinting but engaged distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Further, these studies provided the first glimpse of the evolution of T-cell responses to adjuvanted vaccines in the lungs to define the quantitative, phenotypic and functional attributes of mucosal effector/memory CD8 and CD4 T cells that are associated with effective viral control in the lungs, and protection against H1N1 and H5N1 influenza infections. Studies to determine the transcriptional basis for the disparate differentiation of effector CD8 T cells in different adjuvant groups showed that the expressions of T-bet, IRF-4 and BATF were substantially greater in ADJ and ADJ+CpG groups, compared to GLA and ADJ+GLA groups ( Fig. 1D) . cache = ./cache/cord-103105-iqjksoim.txt txt = ./txt/cord-103105-iqjksoim.txt === reduce.pl bib === id = cord-103046-w8bm4p44 author = Suarez, David L. title = Lack of susceptibility of poultry to SARS-CoV-2 and MERS-CoV date = 2020-06-16 pages = extension = .txt mime = text/plain words = 565 sentences = 44 flesch = 58 summary = Multiple studies have examined the susceptibility of domestic animals to CoV-2 to establish the risk of zoonotic transmission and two studies have shown chickens and 24 Middle East Respiratory Syndrome coronavirus (MERS-CoV), another coronavirus of 26 high concern associated with zoonotic infection, was first detected in patients with severe acute 27 lower respiratory tract disease in Saudi Arabia in 2012. For MERS-CoV, dromedary 35 camels appear to be the primary natural reservoir of infection to humans, but other domestic 36 animals seem to be susceptible to infection (7, 8) . Because poultry are so widespread and have close and extended contact with humans, 39 and other mammals in many production systems, including live animal markets, susceptibility 40 were conducted with SARS-CoV-2 and MERS-CoV in five common poultry species. Susceptibility of ferrets, cats, 109 dogs, and other domesticated animals to SARS-coronavirus 2. Middle East Respiratory Syndrome (MERS), and SARS-114 Middle East 118 respiratory syndrome coronavirus infection in non-camelid domestic mammals. cache = ./cache/cord-103046-w8bm4p44.txt txt = ./txt/cord-103046-w8bm4p44.txt === reduce.pl bib === id = cord-103041-ymr3e60k author = Wu, Yue title = Homeostatic mechanisms regulate distinct aspects of cortical circuit dynamics date = 2019-10-02 pages = extension = .txt mime = text/plain words = 7957 sentences = 423 flesch = 42 summary = To understand how neural circuits exploit various synaptic plasticity and homeostatic mechanisms to decrease and recover both firing rates and correlations during MD, we built a plastic recurrent network model consisting of randomly connected excitatory and inhibitory spiking neurons (Methods). Based on these experimental findings, besides Hebbian plasticity during training, we modeled these two distinct homeostatic mechanisms following MD: (1) synaptic scaling which acts only on excitatory synapses (Turrigiano et al., 1998; Hengen et al., 2013) , and (2) intrinsic plasticity which modifies the intrinsic excitability of both excitatory and inhibitory neurons (Grubb and Burrone, 2010; Campanac et al., 2013) (Methods) . We speculated that this failure to recover correlations in the model network, despite the recovery of firing rates, could be the result of perturbing the structured connectivity between excitatory neurons within assemblies generated through training (Fig. 3B) . cache = ./cache/cord-103041-ymr3e60k.txt txt = ./txt/cord-103041-ymr3e60k.txt === reduce.pl bib === id = cord-103181-my4n0vye author = Valle-Casuso, José Carlos title = Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors date = 2020-04-10 pages = extension = .txt mime = text/plain words = 2171 sentences = 115 flesch = 47 summary = Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. We were also interested in exploring the antiviral capacity of two new BSA, IPPA17-04 and GAC50 163 that impair viral replication through inhibition of de novo pyrimidine biosynthesis in host cells. These results show that cell cultures treated with pyrimidine biosynthesis inhibitors did not 175 exhibit cytopathic effects associated to EAV infection, suggesting that EAV replication is also impaired. To verify that ribavirin, IPPA17-A04 and GAC50 actually block EAV replication, viral genome copies 180 were quantified at 48 h.p.i. Culture supernatants of infected ED cells treated or not with the 181 compounds at different concentrations were analyzed by RT-qPCR. cache = ./cache/cord-103181-my4n0vye.txt txt = ./txt/cord-103181-my4n0vye.txt === reduce.pl bib === id = cord-103112-m6cg67lz author = Schloer, Sebastian title = Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine date = 2020-08-16 pages = extension = .txt mime = text/plain words = 1554 sentences = 91 flesch = 51 summary = As the FIASMA group consists of a large number of small compounds that are well-tolerated and widely used for a broad range of clinical applications, exploring these licensed pharmaceuticals may offer a variety of promising antivirals for host-directed therapy to counteract enveloped viruses, including SARS-CoV-2 and COVID 19. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of 27 acid sphingomyelinase (FIASMA), efficiently inhibited the entry and propagation of SARS-CoV-28 2 in the cell culture model without cytotoxic effects and also exerted potent antiviral activity 29 against two currently circulating influenza A virus subtypes, an effect which was also observed 30 upon treatment with the FIASMAs amiodarone and imipramine. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of 27 acid sphingomyelinase (FIASMA), efficiently inhibited the entry and propagation of SARS-CoV-28 2 in the cell culture model without cytotoxic effects and also exerted potent antiviral activity 29 against two currently circulating influenza A virus subtypes, an effect which was also observed 30 upon treatment with the FIASMAs amiodarone and imipramine. cache = ./cache/cord-103112-m6cg67lz.txt txt = ./txt/cord-103112-m6cg67lz.txt === reduce.pl bib === id = cord-103176-hfd8ur9a author = Frost, H. Robert title = Variance-adjusted Mahalanobis (VAM): a fast and accurate method for cell-specific gene set scoring date = 2020-02-19 pages = extension = .txt mime = text/plain words = 7407 sentences = 305 flesch = 46 summary = Unfortunately, statistical and biological differences between single cell and bulk expression measurements make it challenging to use gene set testing methods originally developed for bulk tissue on scRNA-seq data and progress on single cell-specific methods has been limited. To address this challenge, we have developed a new gene set testing method, variance-adjusted Mahalanobis (VAM), that seamlessly integrates with the Seurat framework and is designed to accommodate the technical noise, sparsity and large sample sizes characteristic of scRNA-seq data. While these methods have proven effective for the analysis of bulk expression data, with GSVA and ssGSEA among the most popular techniques, the application of these methods to scRNA-seq data is limited by three main factors: poor classification performance in the presence of sparsity and technical noise, lack of inference support on the single cell level, and high computational cost (esp. cache = ./cache/cord-103176-hfd8ur9a.txt txt = ./txt/cord-103176-hfd8ur9a.txt === reduce.pl bib === id = cord-103108-vmze2mdx author = Vanheer, Lotte title = Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas date = 2020-09-25 pages = extension = .txt mime = text/plain words = 7967 sentences = 440 flesch = 47 summary = HIGHLIGHTS Reconstruction of gene regulatory networks for human adult pancreatic cell types An interactive resource to explore and visualize gene expression and regulatory states Predicting putative transcription factors driving pancreatic cell identity HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively Because TFs recognize DNA motifs in the genome, one can measure if inferred target genes are expressed within single cells, and therefore quantify the activity of TFs. Such approaches have revealed the regulatory programs in distinct systems including the Drosophila brain (Davie et al , 2018) , cancer (Wouters et al., 2020) , during early mouse embryonic development (Peng et al , 2019) , in a mouse cell atlas (Suo et al., 2018 ) and a human cell atlas (Han et al., 2020) . cache = ./cache/cord-103108-vmze2mdx.txt txt = ./txt/cord-103108-vmze2mdx.txt === reduce.pl bib === id = cord-103180-5hkoeca7 author = Furstenau, Tara N. title = Sample pooling methods for efficient pathogen screening: Practical implications date = 2020-07-16 pages = extension = .txt mime = text/plain words = 3789 sentences = 174 flesch = 59 summary = Sample pooling methods improve the efficiency of large-scale pathogen screening campaigns by reducing the number of tests and reagents required to accurately categorize positive and negative individuals. Here we use computational simulations to determine how several theoretical approaches compare in terms of (a) the number of tests, to minimize costs and save reagents, (b) the number of sequential steps, to reduce the time it takes to complete the assay, (c) the number of samples per pool, to avoid the limits of detection, (d) simplicity, to reduce the risk of human error, and (e) robustness, to poor estimates of the number of positive samples. 25 Due to practical concerns, Dorfman's group testing approach was never applied to 26 syphilis screening because the large number of negative samples had a tendency to 27 dilute the antigen in positive samples below the level of detection [6] . cache = ./cache/cord-103180-5hkoeca7.txt txt = ./txt/cord-103180-5hkoeca7.txt === reduce.pl bib === id = cord-103150-e9q8e62v author = Mishra, Shreya title = Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs date = 2020-11-04 pages = extension = .txt mime = text/plain words = 8216 sentences = 457 flesch = 53 summary = Just like gene-expression profile, inferred gene network could also be used to find differences in two groups of cells(sample) [13] to reveal changes in the regulatory pattern caused due to disease, environmental exposure or ageing. In order to test the hypothesis that graph-based denoising could improve gene-network inference, we first evaluated the performance of our method on bulk expression data-set. Our approach of graph-wavelet based pre-processing of mESC scRNA-seq data-set improved the performance of gene-network inference methods by 8-10 percentage (Fig. 2B) . Similarly in comparison to graph-wavelet based denoising, the other 7 methods did not provided substantial improvement in AUC for overlap among gene-network inferred by two data-sets of mESC (Fig. 2C , supplementary Figure S1B ). However, graph wavelet-based filtering improved the overlap between networks inferred from different batches of scRNA-seq profile of mESC even if they were denoised separately (Fig. 2C , supplementary Figure S1B ). cache = ./cache/cord-103150-e9q8e62v.txt txt = ./txt/cord-103150-e9q8e62v.txt === reduce.pl bib === id = cord-103029-nc5yf6x4 author = Wichmann, Stefan title = Computational design of genes encoding completely overlapping protein domains: Influence of genetic code and taxonomic rank date = 2020-09-25 pages = extension = .txt mime = text/plain words = 8665 sentences = 387 flesch = 52 summary = In this study the artificially designed sequences are compared to their original sequences in terms of amino acid identity, amino acid similarity, Hidden Markov Model profile and secondary structure in order to determine the impact of OLG construction and which sequences are potentially functional. While the previous study [30] tried to estimate an upper limit of how many domains can be successfully overlapped in at least one reading frame and position, here the average success rate for OLG construction is determined instead, which is more relevant in relation to both understanding constraints on the formation rate of naturally occuring OLGs and in assessing the likelihood of successful synthetic creation of OLGs. These results in one sense give an upper estimate of the ease of creating overlaps as the difficulty of obtaining an overlapping gene pair naturally is not directly addressed here. cache = ./cache/cord-103029-nc5yf6x4.txt txt = ./txt/cord-103029-nc5yf6x4.txt === reduce.pl bib === id = cord-103157-xe5ccw9j author = Mayer, David title = Developing and Deploying a Scalable Computing Platform to Support MOOC Education in Clinical Data Science date = 2020-08-27 pages = extension = .txt mime = text/plain words = 4322 sentences = 222 flesch = 53 summary = In response to these challenges we sought to create a hosted computing platform that would both manage student access to restricted materials and accommodate the unique challenges posed by MOOCs. The primary goal of developing the computing platform was to create a system that would allow instructors to restrict and monitor access to sensitive clinical data to only those students who had signed required data use agreements. New students are assigned a unique student id number, provisioned a linux user account on the Computing server (which is linked to their Google account), added to a private Google Group that has been assigned the appropriate IAM roles for accessing course BigQuery datasets, and a platform expiration date calculated (~6mo). We have created a computing platform to support clinical data science MOOC education that has been scalable, globally available, secure, privacy preserving, and generally supported independent access by a large number of students. cache = ./cache/cord-103157-xe5ccw9j.txt txt = ./txt/cord-103157-xe5ccw9j.txt === reduce.pl bib === id = cord-103174-4m3ajc8a author = Okada, Megan title = Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity date = 2020-10-16 pages = extension = .txt mime = text/plain words = 2809 sentences = 148 flesch = 49 summary = Doxycycline (DOX) is a key antimalarial drug thought to kill Plasmodium parasites by blocking protein translation in the essential apicoplast organelle. Exogenous iron rescues parasites and apicoplast biogenesis from first-but not second-cycle effects of 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism distinct from the delayed-death mechanism. We observed that IPP shifted the 48-hour EC50 value of DOX from 5 ± 1 to 12 ± 2 µM 100 (average ± SD of 5 independent assays, P = 0.001 by unpaired t-test) ( Figure 2C and Figure 2 -101 figure supplement 1), suggesting that first-cycle growth defects from 5-10 µM DOX reflect an 102 apicoplast-specific mechanism but that DOX concentrations >10 µM cause off-target defects 103 outside this organelle. cache = ./cache/cord-103174-4m3ajc8a.txt txt = ./txt/cord-103174-4m3ajc8a.txt === reduce.pl bib === id = cord-103163-0rreoh4o author = Smith, Sydni Caet title = Reovirus RNA recombination is sequence directed and generates internally deleted defective genome segments during passage date = 2020-10-22 pages = extension = .txt mime = text/plain words = 8965 sentences = 456 flesch = 46 summary = We determined the titers and RNA segment profiles of reovirus (rsT1L and rsT3D I ) and rotavirus (rsSA11) laboratory strains that had been rescued by reverse genetics then serially passaged ten times, each in triplicate lineages, in cultured cells. The two reoviruses accumulated non-canonical RNAs that retain 5′ and 3′ termini and feature one or more large internal deletions, while the rotavirus rarely accumulated such DVGs. Analyses of next-generation RNA-sequencing data sets from purified rsT1L reovirus RNA revealed many junctions, with hot spots for recombination in specific viral gene segments. Taken together, lin1 RNA profiles suggest non-canonical RNA species that differ in length but have identical termini to the parental segments accumulate variably during reovirus and rotavirus serial passage in cultured cells. cache = ./cache/cord-103163-0rreoh4o.txt txt = ./txt/cord-103163-0rreoh4o.txt === reduce.pl bib === id = cord-103204-gt6upfri author = Hölzer, Martin title = PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection date = 2020-05-20 pages = extension = .txt mime = text/plain words = 1791 sentences = 108 flesch = 42 summary = Summary PoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. A comprehensive evolutionary analysis of significantly positively selected sites consist of several complicated steps, including (1) in-frame alignment; (2) Indel correction; (3) phylogenetic tree calculation; (4) selection of a best-fitting nucleotide substitution * To whom correspondence should be addressed. model; (5) detection of topological incongruence and breakpoint selection to describe putative recombination events; (6) calculation of positively selected sites (ω > 1) under varying models; (7) and their impact on the selective pressure acting on the whole alignment. PoSeiDon comprises an assembly of different scripts and tools ( Fig. 1) that allow for the detection of recombination and positive selection in protein-coding sequences. Here we present PoSeiDon, an easy-to-use Nextflow pipeline for the accurate detection of site-specific positive selection and recombination events in protein-coding sequences. cache = ./cache/cord-103204-gt6upfri.txt txt = ./txt/cord-103204-gt6upfri.txt === reduce.pl bib === id = cord-103271-l9n27ocf author = Carozza, Jacqueline A title = Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date = 2020-05-31 pages = extension = .txt mime = text/plain words = 5664 sentences = 329 flesch = 51 summary = Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. Inspired by the molecular scaffold of a previous inhibitor, QS1, 26, 28 which lacks potency at physiological conditions, we build structure-activity relationships (SAR) around the three sections of the molecule -the zinc-binding head, the core, and the tail -and develop several inhibitors with nanomolar Ki values. Assays used to assess the potency of previously attempted ENPP1 inhibitors are inconsistent 26-34 ; however, developing an appropriate assay is key to determining the utility of the molecules in inhibiting cGAMP degradation under physiological conditions. Since our crystal structure suggests that the zinc-binding phosphonate head and quinazoline tail form the most important interactions with ENPP1, we next sought to explore the core region to achieve optimal geometry between these two functional groups ( Fig. 4a-b) . cache = ./cache/cord-103271-l9n27ocf.txt txt = ./txt/cord-103271-l9n27ocf.txt === reduce.pl bib === id = cord-103208-krann2ir author = Barber-Axthelm, Isaac M title = Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node date = 2020-08-29 pages = extension = .txt mime = text/plain words = 2931 sentences = 146 flesch = 43 summary = In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. We tested if sampling accuracy, and the characterisation of vaccine-elicited immune responses ex vivo, could be improved using tattoo ink to label vaccine-draining LNs in NHPs. Pigtail macaques (Macaca nemastrina) were immunised in the right quadriceps with SARS-CoV-2 spike (100μg) formulated with monophosphoryl lipid A (MPLA) liposomal adjuvant ( 2 9 ) , and were boosted IM in the right and left quadriceps with SARS-CoV-2 spike (100μg) formulated with MPLA and tattoo ink (1.0%). . Animals were additionally immunised in the right and left deltoids with human immunodeficiency virus-1 (HIV-1) fixed trimeric envelope protein (SOSIP) vaccines (100μg) formulated with MPLA and 1.0% tattoo ink (ink in the right deltoid only), with expected drainage to the axillary LNs (Fig 3A) ( cache = ./cache/cord-103208-krann2ir.txt txt = ./txt/cord-103208-krann2ir.txt === reduce.pl bib === id = cord-103187-a255643n author = Mitchell, Evan title = Prophylactic host behaviour discourages pathogen exploitation date = 2019-12-19 pages = extension = .txt mime = text/plain words = 3196 sentences = 343 flesch = 79 summary = Third, and most 253 important, numerical results indicate that the CSS exploitation rateξ changes in a simple 254 way as cost is reduced from its critical value to its natural lower limit at zero (figure 2). When the cost is above its critical value so that no one 298 is engaging in prophylaxis, then this mutant cannot invade a resident population at the CSS 299ξ = √ κ. If we then decrease the cost below its critical value so that individuals begin to 300 take prophylactic measures, the CSS exploitation level decreases away fromξ = √ κ and so 301 the mutant is still unable to invade the resident population. (( -epsil^2* xbar + 1)* ubar * bmax + k * cost )* kappa * xi^2 ... (( -epsil^2* xbar + 1)* ubar * bmax + k * cost )* kappa * xi^2 ... cache = ./cache/cord-103187-a255643n.txt txt = ./txt/cord-103187-a255643n.txt === reduce.pl bib === id = cord-103294-1lrfna4v author = Northrop, Amanda C. title = Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem date = 2020-05-02 pages = extension = .txt mime = text/plain words = 596 sentences = 32 flesch = 47 summary = A model system for understanding ecosystem recovery is the aquatic microecosystem that inhabits the cup-shaped leaves of the pitcher plant Sarracenia purpurea. At low enrichment rates, ecosystems showed a substantial lag in the recovery of [O2] (clockwise hysteresis). At high enrichment rates, we observed a novel response: changes in [O2] were proportionally larger during the recovery phase than during the enrichment phase (counter-clockwise hysteresis). With counter-clockwise hysteresis, rapid reduction of a driver variable following high enrichment rates may be a viable restoration strategy. In ecosystems where hysteresis is counter-clockwise, rapid reduction in a driver variable from high to low levels may be 111 a successful restoration strategy. In contrast, systems that have experienced chronic low-levels of enrichment may exhibit 112 clockwise hysteresis that requires more extreme reductions of the driver variable, or alternative restoration strategies 36 , to 113 restore. cache = ./cache/cord-103294-1lrfna4v.txt txt = ./txt/cord-103294-1lrfna4v.txt === reduce.pl bib === id = cord-103249-k35o3gxe author = Johannsen, Leif title = Robotic light touch assists human balance control during maximum forward reaching date = 2019-11-20 pages = extension = .txt mime = text/plain words = 3082 sentences = 154 flesch = 51 summary = We speculated, therefore, that minimization of the interaction 106 forces and their variability at the contact location during IPT acts as an implicit task constraint and shared goal In the present study, we intended to contrast the effects of human IPT (hIPT) on CR's postural performance 112 against the effects of two different modes of robotic IPT (rIPT) and expected specific costs and benefits on body 113 sway and postural performance due to the robotic response modes. As the coupling 116 between two humans with IPT in terms of the interaction forces is intrinsically more noisy due to each 117 individual's motion dynamics and response delays, we expected that a predictive mode of the robotic system 118 would result in a less noisy haptic coupling and therefore enhance performance in the MFR task, such as greater 119 reaching distance with less body sway. cache = ./cache/cord-103249-k35o3gxe.txt txt = ./txt/cord-103249-k35o3gxe.txt === reduce.pl bib === id = cord-103301-v4l9sovt author = Bloom, David C. title = Immunization by replication-competent controlled herpesvirus vectors date = 2018-04-11 pages = extension = .txt mime = text/plain words = 2332 sentences = 120 flesch = 45 summary = We found that localized activation in 8 mice of efficient but limited replication of a replication-competent controlled herpesvirus 9 vector resulted in a greatly enhanced immune response to the virus or an expressed 10 heterologous antigen. We found that localized activation in 8 mice of efficient but limited replication of a replication-competent controlled herpesvirus 9 vector resulted in a greatly enhanced immune response to the virus or an expressed 10 heterologous antigen. HSV-GS7 replication was also tightly controlled in vivo, two of three groups of mice 8 were administered HSV-GS7 virus (50,000 pfu per mouse) to the footpad, and the mice 9 of one of the latter groups were given ulipristal intraperitoneally (i,p.) as well as, 3 h 10 later, were subjected to a heat treatment to the footpads at 45 0 C for 10 min. cache = ./cache/cord-103301-v4l9sovt.txt txt = ./txt/cord-103301-v4l9sovt.txt === reduce.pl bib === id = cord-103363-efd80dgn author = Mahan, Margaret title = tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports date = 2019-03-21 pages = extension = .txt mime = text/plain words = 2392 sentences = 159 flesch = 44 summary = title: tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports Here, we set out to develop and validate a framework to extract pertinent clinical conditions for traumatic brain injury (TBI) from computed tomography (CT) reports. Materials and Methods We developed tbiExtractor, which extends pyConTextNLP, a regular expression algorithm using negation detection and contextual features, to create a framework for extracting TBI common data elements from radiology reports. The algorithm inputs radiology reports and outputs a structured summary containing 27 clinical findings with their respective annotations. Discussion and Conclusion tbiExtractor is a validated algorithm for extraction of TBI common data elements from radiology reports. At this stage of processing, each sentence in the radiology report will be marked with lexical 245 targets and linked lexical modifiers. With the nature of TBIs, some visible pathologies are only seen on follow-up CTs developed to automate the extraction of TBI common data elements from 438 radiology reports cache = ./cache/cord-103363-efd80dgn.txt txt = ./txt/cord-103363-efd80dgn.txt === reduce.pl bib === id = cord-103350-jj9pc4a6 author = Tang, Pingtao title = An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy date = 2020-05-08 pages = extension = .txt mime = text/plain words = 4041 sentences = 204 flesch = 46 summary = rAd-Tat and LacZ control vectors (2 × 109) were expressed in the kidney of newborn wild type and HIV-transgenic (Tg26) FVB/N mice without significant proteinuria (n = 5 8 per group). Results HIV-Tat induced the expression of HIV-1 genes (env) and heparin binding growth factors in the kidney of HIV-Tg26 mice, and precipitated HIVAN in the first month of life. Summary statement We developed a new inducible mouse model system of childhood HIV-associated nephropathy, and demonstrated that HIV-Tat plays a critical role in this renal disease acting in synergy with other HIV-1 genes and heparin binding cytokines. Therefore, we carried out this study to determine whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and define whether this approach could be used to generate an inducible mouse model system of childhood HIVAN. Our study showed that the activation and basic binding domains of Tat are sufficient to induce the renal expression of HIV-genes and precipitate HIVAN in young mice. cache = ./cache/cord-103350-jj9pc4a6.txt txt = ./txt/cord-103350-jj9pc4a6.txt === reduce.pl bib === id = cord-103320-2rpr7aph author = Bhandari, Bikash K. title = Solubility-Weighted Index: fast and accurate prediction of protein solubility date = 2020-03-26 pages = extension = .txt mime = text/plain words = 4889 sentences = 333 flesch = 50 summary = Results We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli. Protein solubility, at least in part, depends upon extrinsic factors such as ionic strength, temperature and pH, as well as intrinsic factors-the physicochemical properties of the protein sequence and structure, including molecular weight, amino acid composition, hydrophobicity, aromaticity, isoelectric point, structural propensities and the polarity of surface residues (Wilkinson and Harrison 1991; Chiti et al. 2003 ) Among these sets of B-factors, sequence composition scoring using the most recently published set of normalised B-factors produced the highest AUC score ( To improve the prediction accuracy of solubility, we iteratively refined the weights of amino acid residues using the Nelder-Mead optimisation algorithm (Nelder and Mead 1965) . To understand the properties of soluble and insoluble proteins, we determined the enrichment of amino acid residues in the PSI:Biology targets relative to the eSOL sequences (see Methods). cache = ./cache/cord-103320-2rpr7aph.txt txt = ./txt/cord-103320-2rpr7aph.txt === reduce.pl bib === id = cord-103297-4stnx8dw author = Widrich, Michael title = Modern Hopfield Networks and Attention for Immune Repertoire Classification date = 2020-08-17 pages = extension = .txt mime = text/plain words = 14093 sentences = 926 flesch = 57 summary = In this work, we present our novel method DeepRC that integrates transformer-like attention, or equivalently modern Hopfield networks, into deep learning architectures for massive MIL such as immune repertoire classification. DeepRC sets out to avoid the above-mentioned constraints of current methods by (a) applying transformer-like attention-pooling instead of max-pooling and learning a classifier on the repertoire rather than on the sequence-representation, (b) pooling learned representations rather than predictions, and (c) using less rigid feature extractors, such as 1D convolutions or LSTMs. In this work, we contribute the following: We demonstrate that continuous generalizations of binary modern Hopfield-networks (Krotov & Hopfield, 2016 Demircigil et al., 2017) have an update rule that is known as the attention mechanisms in the transformer. We evaluate the predictive performance of DeepRC and other machine learning approaches for the classification of immune repertoires in a large comparative study (Section "Experimental Results") Exponential storage capacity of continuous state modern Hopfield networks with transformer attention as update rule cache = ./cache/cord-103297-4stnx8dw.txt txt = ./txt/cord-103297-4stnx8dw.txt === reduce.pl bib === id = cord-103408-vhrlrd2c author = Mishra, Preet title = Decision Support Systems based on Scientific Evidence: Bibliometric Networks of Invasive Lantana camara date = 2020-08-10 pages = extension = .txt mime = text/plain words = 3304 sentences = 143 flesch = 46 summary = Network approach to decipher large data sets has long been known as one of the best analytical strategies, and this applies equally well for bibliographic information (Shiffrin and Börner, 2004) , with the added benefits of being able to explore, model and restructure literature metadata to draw insights from both static and dynamic representations of individuals, organizations or themes of research (Newman, 2004) . High dimensional literature metadata, when visualized efficiently through networks can reveal communities sharing common node or edge attributes in both coarse-grained and fine-grained routines (Babu et al., 2016) Availability of metadata can often overcome constraints of limited access to full-text and enable one to focus on a lower ease-of-access threshold, i.e. critical information within the title, abstract and citation. Here we present case studies from invasive plant species bibliographic metadata and share how emerging co-authorship networks can improve and inform decisions, and how diverse network visualizations can be integrated as modules in a DSS. cache = ./cache/cord-103408-vhrlrd2c.txt txt = ./txt/cord-103408-vhrlrd2c.txt === reduce.pl bib === id = cord-103213-oinumv1z author = Kalantar, Katrina L. title = IDseq – An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring date = 2020-04-18 pages = extension = .txt mime = text/plain words = 10494 sentences = 562 flesch = 46 summary = The IDseq Portal accepts raw mNGS data, performs host and quality filtration steps, then executes an assembly-based alignment pipeline which results in the assignment of reads and contigs to taxonomic categories. First, relevant QC metrics and pipeline run information, including the number of reads remaining at each step of the host and quality filtering steps as well as estimates of internal control abundances are provided for each sample (Figure 2AB, Methods) . The idseq-bench tool was used to generate 17 simulated NGS samples from Rhinovirus C genomes at varying levels of divergence (after in-silico forward evolution from a reference sequence obtained from the NCBI database), ranging from 100% identical to the reference sequence to 25% similar (at the nucleotide level) (Methods, Figure 4A , Table S3 ). cache = ./cache/cord-103213-oinumv1z.txt txt = ./txt/cord-103213-oinumv1z.txt === reduce.pl bib === id = cord-103465-6udhvl9n author = Schierding, William title = Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date = 2020-04-13 pages = extension = .txt mime = text/plain words = 6450 sentences = 323 flesch = 41 summary = Results 140 genetic variants with regulatory potential are associated with cohesin loci Mitotic cohesin genes (SMC1A, SMC3, STAG1, STAG2, and RAD21), meiotic cohesin genes (SMC1B, STAG3, REC8, and RAD21L1), cohesin support genes (WAPL, NIPBL, PDS5A, PDS5B, and MAU2) and CTCF were investigated to determine if they contain non-coding genetic variants (SNPs) that make contact in 3D with genes and therefore could directly affect gene expression (GWAS-attributed and eQTL-attributed; Table 1, Table S1 ). Intriguingly, Haploreg motif prediction identified 16 of the 209 variants (7 different loci: MAU2, PDS5B, REC8, SMC1B, STAG3, RAD21L1, STAG1) as residing within protein binding domains associated with cohesin-related DNA interactions (i.e. RAD21, SMC3, and CTCF). Pathway enrichment implicates coordinated regulation of cohesin with essential cell cycle genes CoDeS3D identified 140 variants as being physically connected to, and associated with the expression levels of 310 genes (243 genes from eQTL-attributed variants, 141 from GWAS-attributed variants, and 74 overlap) across 6,795 significant tissue-specific regulatory connections (FDR p<0.05). cache = ./cache/cord-103465-6udhvl9n.txt txt = ./txt/cord-103465-6udhvl9n.txt === reduce.pl bib === id = cord-103343-k4v5ksvq author = Naim, Nikki title = NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity date = 2020-09-11 pages = extension = .txt mime = text/plain words = 823 sentences = 62 flesch = 54 summary = title: NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity Aging and immunity are inextricably linked and many genes that extend lifespan also enhance immunoresistance. Here, we demonstrate that the Caenorhabditis elegans pro-longevity factor, NHR-49, also promotes resistance against Pseudomonas aeruginosa, but modulates immunity and longevity by spatially and mechanistically distinct mechanisms. NHR-49 expression is increased by germline ablation, an intervention that extends lifespan, but lowered by pathogen exposure. NHR-49 acted in multiple somatic tissues to promote longevity, whereas, it's pro-immunity function was mediated by neuronal expression. Thus, NHR-49 targets share the largest overlap with genes whose 182 In this study, we demonstrate that NHR-49 is a pro-longevity factor that modulates 368 lifespan and immunity through distinct mechanisms. In fertile, nhr-49 single 393 mutants, immunity was restored by presence in neurons or intestine, but lifespan 394 could be rescued from other tissues as well. elegans lifespan in a NHR-49/PPARalpha-dependent manner cache = ./cache/cord-103343-k4v5ksvq.txt txt = ./txt/cord-103343-k4v5ksvq.txt === reduce.pl bib === id = cord-103377-j1mmx7k7 author = Karasik, Agnes title = Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences date = 2020-09-11 pages = extension = .txt mime = text/plain words = 11779 sentences = 646 flesch = 58 summary = Since it was reported that RNase L activation increased translation of 3'UTR regions downstream of stop codons by interfering with factors that promote translation termination (eRF3) or ribosome recycling (ABCE1) (Le Roy et al., 2005) , we assessed the level of ribosome footprints in 3'UTRs. This level was assayed by computing the ratio of footprints in every 3'UTR relative to its respective main ORF within the coding sequence (density ratio, 3'UTR:ORF) for each transcript . The similarity in the effects suggests that translation of non-canonical regions occurs when RNase L is activated via naturally produced 2-5A from broad activation of the antiviral response by double-stranded RNAs. It should be noted that poly I:C treatment did result in slightly elevated 3'UTR ribosome footprints on some genes in a RNase L KO cell line (Supplemental Figure 4A ). cache = ./cache/cord-103377-j1mmx7k7.txt txt = ./txt/cord-103377-j1mmx7k7.txt === reduce.pl bib === id = cord-103396-jiuqk6kg author = Adler, Paul N. title = Short distance non-autonomy and intercellular transfer of chitin synthase in Drosophila date = 2020-05-26 pages = extension = .txt mime = text/plain words = 4072 sentences = 246 flesch = 63 summary = In experiments where we imaged Kkv::NG in living pupae we noticed fluorescent puncta in the 219 extracellular space between the pupal cuticle and the epidermal cells that were in the process of 220 synthesizing the adult cuticle (Fig. 6BC ). No fluorescence was observed in the region 227 between the pupal cuticle and the apical surface of the epithelial cells in Ore-R pupae (Fig. 6EF) . We also observed puncta in very young pupae (20 237 hr awp) prior to the detachment of the epithelial cells from the pupal cuticle (Fig. S6B) . These animals showed a large 253 number of fluorescent puncta present in the space between the pupal cuticle and the apical surface of 254 the epithelial cells ( Fig 6GHI) . However, in carrying out these in vivo imaging experiments we observed that the autofluorescence of 259 the thoracic and abdominal pupal cuticles was quite distinct (Fig S8) . cache = ./cache/cord-103396-jiuqk6kg.txt txt = ./txt/cord-103396-jiuqk6kg.txt === reduce.pl bib === id = cord-103504-ucqqpra5 author = Zhang, Zhe title = The conserved ER-transmembrane protein TMEM39 coordinates with COPII to promote collagen secretion and prevent ER stress date = 2020-09-20 pages = extension = .txt mime = text/plain words = 2877 sentences = 184 flesch = 55 summary = From a genome-wide RNAi screen for 54 genes affecting ER stress response, we previously identified tmem-131 that defines a 55 broadly conserved family of proteins important for procollagen assembly and secretion 56 (22). RNAi knock-down of sec-23 and most other COPII genes 340 recapitulated the tmem-39 loss-of-function phenotypes in constitutively high ER stress 341 response, defective collagen secretion and sensitivity to osmolality stress in C. We also noticed that RNAi knock-down of many COPII related genes, such 343 as sec-23, sec-24.1, npp-20, sar-1, sec-12, rab-5 and trpp-8 caused more severe 344 phenotypes than tmem-39 RNAi, leading to lethality or developmental arrest that 345 prevent collagen phenotype analysis (Table 1) Recent work showed that TMEM39A facilitates the ER-to-Golgi transport of SAC1 and 355 regulates autophagosome formation (28). We found that RNAi knock-down of 356 autophagy related genes, such as sac-1 and let-363, caused autophagy induction but 357 did not affect the ER stress response or collagen secretion (Fig 6) . cache = ./cache/cord-103504-ucqqpra5.txt txt = ./txt/cord-103504-ucqqpra5.txt === reduce.pl bib === id = cord-103345-v555a2ll author = Taylor, Adrian title = The novel roles of choline transporter-like 1 and 2 in ethanolamine transport date = 2020-08-28 pages = extension = .txt mime = text/plain words = 3722 sentences = 210 flesch = 53 summary = These data firmly established that CTL1 and CTL2 are the first identified ethanolamine transporters in the whole cells and mitochondria, with intrinsic roles in de novo PE synthesis by the CDP-Etn Kennedy pathway and compartmentation of intracellular ethanolamine. PC and PE are synthesized de novo by CDP-Cho and CDP-Etn branches of the Kennedy pathway in which the extracellular substrates choline (Cho) and ethanolamine (Etn) are actively transported into the cell, phosphorylated and coupled with diacylglycerols (DAG) to form the final phospholipid product. While multiple transport systems have been established for Cho, Etn transport is poorly characterized and there is no single gene/protein assigned a transport function for mammalian Etn. Cho transport for membrane phospholipid synthesis is mediated by Cho transporter like protein CTL1/SLC44A1 (3) . M1 and M2 cells only express CTL2 and at levels similar to Ctrl and Cos 7 cells, and do not have a functional CTL1 protein ( Fig. 2A,D) , strongly implicating CTL2 as responsible for the low affinity Etn transport. cache = ./cache/cord-103345-v555a2ll.txt txt = ./txt/cord-103345-v555a2ll.txt === reduce.pl bib === id = cord-103306-1wc3f1rl author = Sengupta, Sourodip title = Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine coronavirus-induced neuroinflammation date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3579 sentences = 229 flesch = 53 summary = Elevated mRNA and protein levels of tissue inhibitors of metalloproteinases 1 (TIMP-1) in MHV-A59 infection are suggestive of a TIMP-1 mediated host antiviral response. Total RNA was isolated from mock and virus-infected brain tissues 238 for expression analysis of viral nucleocapsid and Mmp genes through RT-qPCR. MMPs. To understand the regulation of MMPs upon MHV-A59 infection, we also 254 considered the gene expression of TIMPs. As described above, total RNA from brain samples 255 of mock and MHV-A59 infected mice were subjected to RT-qPCR using specific primers 256 12 (Table 1) to determine the transcript levels of Timp1, Timp2, Timp3, and Timp4. While Timp1 mRNA 260 followed a similar expression pattern as the Mmps following MHV-A59 infection-induced 261 inflammation, its protein levels remained high throughout post-infection, as shown in the 262 representative figure (Fig. 2, B) . Transcript levels of Parkinson's disease 7 312 (Park7) gene were significantly upregulated following RSA59 infection and remained 313 elevated p.i compared to mock-infected samples (Fig. 7, A; p<0.05). cache = ./cache/cord-103306-1wc3f1rl.txt txt = ./txt/cord-103306-1wc3f1rl.txt === reduce.pl bib === id = cord-103430-x6zzuu7v author = Contu, Lara title = Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date = 2020-10-12 pages = extension = .txt mime = text/plain words = 8272 sentences = 461 flesch = 56 summary = Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus' hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. Gene ontology (GO) enrichment analyses of protein complexes that could 10 form between the identified host interactors revealed highly significant GO terms related to 11 translation and Nonsense-mediated mRNA Decay (NMD). In addition to ribosomal proteins, many other RNA binding proteins were also 37 identified as having a potential role in SFV replication (Figure 3a (nsP1, nsP2, nsP3-Z, nsP4, capsid and Env) as well as for the merged list (All baits) was also applied. cache = ./cache/cord-103430-x6zzuu7v.txt txt = ./txt/cord-103430-x6zzuu7v.txt === reduce.pl bib === id = cord-103502-asphso2s author = Herrgårdh, Tilda title = An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow date = 2020-10-21 pages = extension = .txt mime = text/plain words = 8160 sentences = 409 flesch = 60 summary = Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. However, neither this model, nor any of the previously mentioned multi-level models, have subdivided the glucose uptake into the individual contributions of all of the main insulin-responding and glucose-utilizing organs: adipose tissue, muscle, and liver. The final combined model (Q4) can fit to all of the new data for glucose uptake in all organs (Fig 6) , as well as to all previous data, such as the postprandial glucose and insulin fluxes and concentrations in (Dalla Man et al. cache = ./cache/cord-103502-asphso2s.txt txt = ./txt/cord-103502-asphso2s.txt === reduce.pl bib === id = cord-103435-yufvt44t author = van Aalst, Marvin title = Constructing and analysing dynamic models with modelbase v1.0 - a software update date = 2020-10-02 pages = extension = .txt mime = text/plain words = 4085 sentences = 208 flesch = 37 summary = Background Computational mathematical models of biological and biomedical systems have been successfully applied to advance our understanding of various regulatory processes, metabolic fluxes, effects of drug therapies and disease evolution or transmission. Results and Discussion We provide here the update on the development of modelbase, a free expandable Python package for constructing and analysing ordinary differential equation-based mathematical models of dynamic systems. Most recently, deterministic models simulating the dynamics of infectious diseases gained the interest of the general public during our combat of the Covid-19 pandemic, when a large number of ODE based mathematical models has been developed and discussed even in nonscientific journals (see for example [3] [4] [5] ). Implementation modelbase is a Python package to facilitate construction and analysis of ODE based mathematical models of biological systems. We are presenting here updates of our modelling software that has been developed to simplify the building process of mathematical models based on ODEs. modelbase is fully embedded in the Python programming language. cache = ./cache/cord-103435-yufvt44t.txt txt = ./txt/cord-103435-yufvt44t.txt === reduce.pl bib === id = cord-103341-q7yqnvm2 author = MacPherson, Ailene title = A General Birth-Death-Sampling Model for Epidemiology and Macroevolution date = 2020-10-11 pages = extension = .txt mime = text/plain words = 2672 sentences = 167 flesch = 55 summary = As an illustration of the utility of our mathematical approach, we use our approach to derive a yet unstudied variant of the birth-death process in which the key rates emerge deterministically from a classic susceptible infected recovered (SIR) epidemiological model. Similarly, in the case of past CSAs we must 99 include the probability, r l , that sampled hosts are removed from the infectious pool during the CSA at time 100 ary case to explicitly model the collection of samples from the fossil record (e.g., the fossilized birth-death 102 process [19]). Step 6: Conditioning the likelihood -Finally, we condition the likelihood on observing at least one lineage 285 given the TMRCA, Here we derive a phylogenetic birth-death-sampling model in a more general form than previously attempted, 294 making as few assumptions about the processes that generated the data as possible. cache = ./cache/cord-103341-q7yqnvm2.txt txt = ./txt/cord-103341-q7yqnvm2.txt === reduce.pl bib === === reduce.pl bib === id = cord-103422-ys846i99 author = Xu, Xinhui title = CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date = 2020-05-13 pages = extension = .txt mime = text/plain words = 4258 sentences = 308 flesch = 60 summary = In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. When target DNA is bound by a pair of dCas9-sgRNA complexes, the dCas9-sgRNA-DNA complex will be captured on surface of beads or microplate via annealing between an oligonucleotide coupled on solid supports and capture sequence of sgRNAa. Then the captured dCas9-sgRNA-DNA complex is reported by a kind of signal reporter captured by the capture sequence of sgRNAb. This method was validated by detecting DNA of bacteria, cancer cell and virus. We compared the HPV detection results of these 31 clinical samples tested by Beads-HCR CADD and PCR-reverse dot hybridization method that was performed by Jinling Hospital (Fig. 4C ). These results indicate that Beads-HCR CADD can be used to detect hrHPV infections in clinical samples with high sensitivity and specificity. cache = ./cache/cord-103422-ys846i99.txt txt = ./txt/cord-103422-ys846i99.txt === reduce.pl bib === id = cord-103511-31njndob author = Broggi, Achille title = Type III interferons disrupt the lung epithelial barrier upon viral recognition date = 2020-05-05 pages = extension = .txt mime = text/plain words = 3886 sentences = 283 flesch = 61 summary = Accordingly, sorted lung resident dendritic cells express 192 high levels of IFN-λ transcript after 5 days of poly (I:C) treatment, in contrast to epithelial cells, 193 alveolar macrophages and monocytes (Fig. 4A) , which, instead, express inflammatory cytokines (Fig. S8A, B) . Moreover, diphtheria toxin (DT)-mediated depletion of 195 CD11c + cells in CD11c-DT receptor (DTR) mice was sufficient to completely abolish IFN-λ 9 transcript and protein upregulation upon 6 days of poly (I:C) treatment (Fig. 4B, C) , while production remained unaltered (Fig. S8C with the response measured in vivo, TLR7 stimulation did not induce IFN production while it 207 induced upregulation of pro-inflammatory cytokines, and intracellular delivery of poly (I:C) induced 208 high levels of IFN-I but not IFN-λ (Fig.4D, Fig. S9A , B). Dendritic cells sorted from Ticam1 -/mice treated with poly (I:C) for six 222 days did not express appreciable levels of IFN-λ transcripts while still produced type I interferons 223 ( Fig. 4E, F) . cache = ./cache/cord-103511-31njndob.txt txt = ./txt/cord-103511-31njndob.txt === reduce.pl bib === id = cord-103460-5thh6syt author = Carlson, Colin J. title = Climate change will drive novel cross-species viral transmission date = 2020-07-14 pages = extension = .txt mime = text/plain words = 1438 sentences = 74 flesch = 52 summary = In addition, changing climate and land use are already driving geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species4,5. Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of geographic range shifts for 3,870 mammal species under climate change and land use scenarios for the year 2070. Range-shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, driving the cross-species transmission of novel viruses at least 4,000 times. Even with dispersal limits, these first encounters are predicted to produce al-207 most one hundred new viral sharing events (RCP 2.6: 96 ± 2.3; RCP 8.5: 86 ± 3.9) that might 208 include ZEBOV, and which cover a much broader part of Africa than the current zoonotic niche 209 of Ebola 68 . cache = ./cache/cord-103460-5thh6syt.txt txt = ./txt/cord-103460-5thh6syt.txt === reduce.pl bib === id = cord-103358-1hbw3yo3 author = Gisbert-Muñoz, Sandra title = MULTIMAP: Multilingual picture naming test for mapping eloquent areas during awake surgeries date = 2020-06-08 pages = extension = .txt mime = text/plain words = 4348 sentences = 196 flesch = 45 summary = Although the use of object naming tasks is widespread across surgical teams in many different geographical locations, heterogeneity in the stimuli selection criteria of previous batteries (i.e., differences in picture size, color, image quality, name agreement), in addition to the use of morphologically and typologically different languages across different studies (see supplementary material for a table review), has greatly hindered the comparison and generalization of results. Notably, direct cortical stimulation studies also show this double dissociation when object and action naming tasks are used, and allow for the identification of distinct territories in frontal and temporal brain areas in which stimulation selectively impairs verb or noun production (Corina et al., 2005; Crepaldi, Berlingeri, Paulesu, & Luzzatti, 2011; Lubrano et al., 2014; J. To address this need, we developed the MULTIMAP test, a multilingual picture naming task including both objects and actions for mapping eloquent areas during awake brain surgery. cache = ./cache/cord-103358-1hbw3yo3.txt txt = ./txt/cord-103358-1hbw3yo3.txt === reduce.pl bib === id = cord-103417-2uinislh author = Doi, Hideyuki title = On-site eDNA detection of species using ultra-rapid mobile PCR date = 2020-10-01 pages = extension = .txt mime = text/plain words = 1507 sentences = 91 flesch = 50 summary = Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Ultra-rapid methods from DNA collection to detection are still not well developed (1), especially for environmental DNA (eDNA) analysis, which uses water or soil samples to track the presence of target species (2, 3) . Here, we developed a new innovative method for the field processing of eDNA samples and measurements using an ultra-rapid mobile PCR platform (hereafter, mobile PCR) to reduce the measurement time to 30 min and maintain high detectability of aquatic organisms. We compared the on-site eDNA measurement to the laboratory extraction and detection using a benchtop qPCR platform and the national survey to confirm the performance. Our ultra-rapid on-site eDNA extraction and measurement method using mobile PCR successfully detected the eDNA of H. cache = ./cache/cord-103417-2uinislh.txt txt = ./txt/cord-103417-2uinislh.txt === reduce.pl bib === id = cord-103524-1w9tdhdd author = Hao, Siyuan title = Establishment of a Replicon System for Bourbon Virus and Identification of Small Molecules that Efficiently Inhibit Virus Replication date = 2020-04-25 pages = extension = .txt mime = text/plain words = 4241 sentences = 237 flesch = 61 summary = By using the luciferase reporter, we screened a few small molecule compounds of anti-endonuclease that inhibited the nicking activity by parvovirus B19 (B19V) NS1, as well as FDA-approved drugs targeting the RdRP of influenza virus. Our results demonstrated that myricetin, and an anti-B19V NS1 nicking inhibitor, efficiently inhibited the RdRP activity of BRBV and virus replication. We then used the replicon reporter to examine anti-influenza drugs that target viral RNA-dependent RNA polymerase (RdRP) and endonuclease inhibitors of human parvovirus B19 (B19V) for inhibition of BRBV RdRP activity and BRBV replication in HEK293T and Vero cells. BRBV GFP reporter assay: pHW-ΔCMV-GP-GFP was co-transfected with the four pcDNA-PA, PB1, PB2, and NP plasmids into HEK293T cells confluent in six-well plates. BRBV luciferase reporter assay: pHW-ΔCMV-GP-gLuc and the four pcDNA-based plasmids were co-transfected into HEK293T cells in 96-well plate. cache = ./cache/cord-103524-1w9tdhdd.txt txt = ./txt/cord-103524-1w9tdhdd.txt === reduce.pl bib === id = cord-103509-hynnba03 author = Wong, Ten-Tsao title = A self-assembled protein nanoparticle serving as a one-shot vaccine carrier date = 2020-09-18 pages = extension = .txt mime = text/plain words = 3187 sentences = 148 flesch = 48 summary = From these two clues, it was hypothesized that AH3-GFP fusion protein form stable protein complex through hydrophobic interaction mediated by N-terminal AH3 peptide. Using the same protocol, AH3-GFP was found to co-sedimented with the bacterial membrane (Fig. S3A) as well as the AH3-sfGFP-hM2e fusion protein but not a free GFP protein (Fig S3B) These results are consistent with our protein structure modeling that Arg11 serves as a main contact point for dimer stacking also it mediates the electrostatic interaction with mutated Glu13 (Fig. 3E ). These results suggest that the two point mutations of AH3 in I8L and K13E enable the formation of a stable, high antigenic protein complex that stimulates long lasting immune responses in a single immunization. The result suggests that although carrier protein AH3-sfGFP also has high antigenicity, it did not interfere with the immune response against the heterologous protein, hM2e (Fig. 5B, 5C) cache = ./cache/cord-103509-hynnba03.txt txt = ./txt/cord-103509-hynnba03.txt === reduce.pl bib === id = cord-103421-46owvqw8 author = Saunders, Jaclyn K. title = METATRYP v 2.0: Metaproteomic Least Common Ancestor Analysis for Taxonomic Inference Using Specialized Sequence Assemblies - Standalone Software and Web Servers for Marine Microorganisms and Coronaviruses date = 2020-05-21 pages = extension = .txt mime = text/plain words = 5733 sentences = 237 flesch = 37 summary = Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). This feature previously existed in METATRYP v 1 for generating peptide redundancy tables within the "Genome" sequencing data category and was used to show the relatively low occurrence of shared peptides across disparate taxa in the open ocean microbiome [1] . cache = ./cache/cord-103421-46owvqw8.txt txt = ./txt/cord-103421-46owvqw8.txt === reduce.pl bib === id = cord-103432-cdmoazrl author = Richardson, Eve title = A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies date = 2020-06-02 pages = extension = .txt mime = text/plain words = 6556 sentences = 375 flesch = 51 summary = To test the ability of paratyping and clonotyping to group antibodies that target the same epitope we performed a test in a single-cell (paired VH/VL) data set of 1290 antibodies isolated from genetically engineered mice that have a full set of human immunoglobulin variable region genes [31] immunised with Pertussis toxoid (PTx). Each of the PTx-binders is referred to as a "probe" antibody; sequences that are within the same paratype or clonotype as the probe are predicted to bind PTx. The precision and recall of the two methods (calculated over the aggregate of predictions) for repertoire mining are comparable ( Figure 2 , Table 1 ). In a test system of transgenic mice immunised with Pertussis toxoid (PTx), we show for the first time that prediction and comparison of paratopes can be used to group antigen-specific antibodies in both an enriched, single-cell data set and non-enriched bulk heavy chain repertoires. cache = ./cache/cord-103432-cdmoazrl.txt txt = ./txt/cord-103432-cdmoazrl.txt === reduce.pl bib === id = cord-103462-z3d9lcar author = Wang, Shiyu title = CD4+ T cell subsets present stable relationships in their T cell receptor repertoires date = 2020-11-02 pages = extension = .txt mime = text/plain words = 2934 sentences = 158 flesch = 59 summary = Here, we examined the features of TCR beta (TCRB) repertoire of the top clones within naïve, memory and regular T cell (Treg) subsets: repertoire structure, gene usage, length distribution and sequence composition. To unveil the influence of differentiation on TCR repertoire, we analyzed the sequencing 68 data of TCR beta (TCRB) chain of NT, ET, EMT, CMT, Tscm and Treg. It suggests 232 that the length distribution of TCRB repertoire of NT is highly skewed in these less-233 differentiated memory cells ( Figure 4B ). We detected the 320 relationships among the TCRB repertoire of top1000 clones of naïve, memory and Treg subsets 321 (including NT, ET, Tcm, Tem, Tscm ET and Treg) by estimating the repertoire structure, the 322 germline gene usage, the sequence composition (K-mer) and public CDR3 clone usage. In our study, public clones from NT are less maintained in 359 differentiated subsets, and SVM analyses indicate that sequence composition in memory 360 cache = ./cache/cord-103462-z3d9lcar.txt txt = ./txt/cord-103462-z3d9lcar.txt === reduce.pl bib === id = cord-103497-1ls2dvzy author = Ganier, C title = CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals date = 2020-05-29 pages = extension = .txt mime = text/plain words = 1427 sentences = 90 flesch = 53 summary = title: CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals To define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 as well as other genes implicated in the cellular entry of SARS-Cov-2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). The ACE2 receptor has been shown to mediate uptake of the virus responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in human cells (Hoffmann, Kleine-Weber, Schroeder, et al. In order to define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). cache = ./cache/cord-103497-1ls2dvzy.txt txt = ./txt/cord-103497-1ls2dvzy.txt === reduce.pl bib === id = cord-103448-xa5zgkd3 author = Adachi, Hiroaki title = Jurassic NLR: conserved and dynamic evolutionary features of the atypically ancient immune receptor ZAR1 date = 2020-10-12 pages = extension = .txt mime = text/plain words = 9758 sentences = 484 flesch = 48 summary = The phylogenetic tree was generated in MEGA7 by the neighbour-joining method using NB-ARC domain sequences of ZAR1-like proteins identified from the prior BLAST searches and 1019 NLRs identified from 6 representative plant species, taro, stout camphor, columbine, tomato, sugar beet and Arabidopsis. The overall conservation of the 120 ZAR1 orthologs enabled us to perform phylogenetic analyses using the full-length protein sequence and not just the NB-ARC domain as generally done with NLRs ( ZAR1 phylogenetic tree with well-supported branches that generally mirrored established phylogenetic relationships between the examined plant species (Smith and Brown, 2018; Chaw et al., 2019) . Taken together, based on the conserved motifs depicted in Figure 3A , we propose that angiosperm ZAR1 orthologs share the main functional features of Arabidopsis ZAR1: 1) effector recognition via RLCK binding, 2) remodelling of intramolecular interactions via ADP/ATP switch, 3) oligomerisation via the NBD-NBD interface and 4) α1 helix/MADA motifmediated activation of hypersensitive cell death. cache = ./cache/cord-103448-xa5zgkd3.txt txt = ./txt/cord-103448-xa5zgkd3.txt === reduce.pl bib === id = cord-103567-nh9i28lu author = Vanachayangkul, Pattaraporn title = Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques date = 2020-04-29 pages = extension = .txt mime = text/plain words = 3686 sentences = 193 flesch = 62 summary = title: Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (IC50 = 10.42 μM) and hypnozoites (IC50 = 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for seven consecutive days was evaluated for prophylaxis or radical cure of Plasmodium cynomolgi liver-stages in Rhesus macaques. Approximately 3 weeks later, a second relapse occurred 174 in all negative control and ivermectin high-and low-dose treated macaques with no significant 175 differences for time to blood-stage parasitemia or treatment (Log-Rank (Mantel Cox) test P > 176 0.05). If a relapse occurs, 397 and blood-stage parasitemia reaches >5,000 parasites per µl, then macaques received seven 398 days of chloroquine (10mg/kg) plus ivermectin (1.2 mg/kg) for both the low-and high-dose 399 groups. cache = ./cache/cord-103567-nh9i28lu.txt txt = ./txt/cord-103567-nh9i28lu.txt === reduce.pl bib === id = cord-103554-11avjsqu author = Davies, Jennifer L title = Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles date = 2019-10-17 pages = extension = .txt mime = text/plain words = 5335 sentences = 288 flesch = 56 summary = The aim of this study was to evaluate the extent to which transcranial magnetic stimulation (TMS) can identify discrete cortical representation of lower-limb muscles in healthy individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil could not reliably identify discrete cortical representations of resting lower-limb muscles when responses were measured using bipolar surface electromyography. Cortical representation was 4 mapped for seven resting lower-limb muscles involved in control of the knee joint (rectus femoris, vastus lateralis, vastus medialis, medial hamstring, lateral hamstring, medial gastrocnemius, and lateral gastrocnemius) and was quantified using size, CoG, hotspot and number of discrete peaks. The current results indicate bipolar surface EMG used with TMS delivered through a doublecone coil cannot reliably identify discrete cortical representation of lower-limb muscles in young, healthy individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil cannot reliably identify discrete cortical representations of resting lower-limb muscles when MEPs are measured using bipolar surface EMG. cache = ./cache/cord-103554-11avjsqu.txt txt = ./txt/cord-103554-11avjsqu.txt === reduce.pl bib === id = cord-103563-7a3wdduq author = Nunez-Bajo, Estefania title = Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens date = 2020-03-25 pages = extension = .txt mime = text/plain words = 4535 sentences = 211 flesch = 44 summary = Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. cache = ./cache/cord-103563-7a3wdduq.txt txt = ./txt/cord-103563-7a3wdduq.txt === reduce.pl bib === id = cord-103538-vh6ma7k7 author = Smaldino, Paul E. title = Coupled Dynamics of Behavior and Disease Contagion Among Antagonistic Groups date = 2020-10-05 pages = extension = .txt mime = text/plain words = 4978 sentences = 257 flesch = 49 summary = We analyze a simple model of coupled behavior-change and infection in a structured population characterized by homophily and outgroup aversion. While we might expect strong selection-both biological and cultural-for adaptive responses to epidemics, complications such as the potentially differing time 33 scales of culture and disease transmission and the existence of social structures that shape adoption may complicate convergence to adaptive behavioral solutions. Unlike a disease, which is reasonably modeled as equally transmissible between any susceptible-infected pairing, where behavior is concerned, susceptible individuals are more likely to adopt when interacting with in-126 group adopters, but less likely to adopt when interacting with outgroup adopters. Not so with outgroup aversion, in which the peak infection rates increase relative to the low homophily case ( Figure 3E , F). However, when R 0 is high enough and outgroup aversion induces 258 group differences in behavior adoption, strong homophily among group 2 can lead to larger, albeit delayed, epidemics in the initially-uninfected segment of the population. cache = ./cache/cord-103538-vh6ma7k7.txt txt = ./txt/cord-103538-vh6ma7k7.txt === reduce.pl bib === id = cord-103618-cl7evbr3 author = Wang, Yingxue title = The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal respiratory infection by influenza A virus at epithelial surfaces date = 2020-05-07 pages = extension = .txt mime = text/plain words = 5685 sentences = 324 flesch = 51 summary = Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high Introduction Influenza A virus (IAV) is a respiratory pathogen of major global public health concern (Yamayoshi & Kawaoka, 2019). These mice, which lack non-canonical autophagy in phagocytic cells ( δWD mice infected with IAV appeared to be unable to resolve inflammatory responses resulting in sustained expression of pro-inflammatory cytokines, morbidity and 10 a striking lung pathology characterized by profuse migration of neutrophils into the airway at day 3 followed by macrophages on day 7. cache = ./cache/cord-103618-cl7evbr3.txt txt = ./txt/cord-103618-cl7evbr3.txt === reduce.pl bib === id = cord-103540-x18pz2uz author = Yellman, Christopher M. title = Precise replacement of Saccharomyces cerevisiae proteasome genes with human orthologs by an integrative targeting method date = 2020-03-26 pages = extension = .txt mime = text/plain words = 6426 sentences = 335 flesch = 49 summary = title: Precise replacement of Saccharomyces cerevisiae proteasome genes with human orthologs by an integrative targeting method We used the IT method to introduce phosphorylation site mutations into the gene SPO12 from oligonucleotide repair templates, and to precisely replace essential yeast proteasome genes with their human orthologs. The cassettes, amplified by PCR with flanking target identity, can be integrated into a yeast chromosomal target locus by high-efficiency transformation 36 and selected for by complementation of a ura3 mutation in the host strain. We have previously shown, in plasmid-based complementation tests, that many human genes encoding subunits of the proteasome can functionally replace their yeast orthologs under the control of a strong constitutive yeast promoter and terminator 30 . The IT4 cassettes were then replaced by inducing I-SceI and transforming with PCR-amplified human ORFs, flanked by homology to the promoter and terminator of the yeast gene. cache = ./cache/cord-103540-x18pz2uz.txt txt = ./txt/cord-103540-x18pz2uz.txt === reduce.pl bib === id = cord-103683-xcsal8vk author = Rafie, K. title = The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children date = 2020-10-16 pages = extension = .txt mime = text/plain words = 6635 sentences = 354 flesch = 53 summary = The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Compared to the two other reported structures of human adenoviruses, HAdV-C5 (PDB: 6B1T (20) ) and HAdV-D26 (PDB: 5TX1(21)), the sequence identity of the capsid proteins ranges from 30-80% (Supplementary Table 3 ). The HAdV-F41 penton base undergoes assembly-induced conformational changes Located on the five-fold symmetry axes of adenovirus capsids, the penton base (PB) protein forms a homopentamer that contains integrin-binding motifs and serves as an assembly hub connecting the icosahedral capsid to the fibers (Fig. 1A) . The DNA-binding protein V is located at a conserved position at the inner face of the capsid After initial model building of the virion at pH=7.4, the asymmetric unit contained five peptide chains that still had not been assigned an identity. cache = ./cache/cord-103683-xcsal8vk.txt txt = ./txt/cord-103683-xcsal8vk.txt === reduce.pl bib === id = cord-103517-1itisiup author = Kwesi-Maliepaard, Eliza Mari title = The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells date = 2019-11-18 pages = extension = .txt mime = text/plain words = 7875 sentences = 419 flesch = 54 summary = T-cell specific ablation of Dot1L resulted in loss of naïve CD8+ T cells and premature differentiation towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. Analysis of CD8 + T cell subsets in the spleen revealed that Dot1L-KO mice showed a severe loss of naïve (CD44 -CD62L + ) CD8 + T (T N ) cells which was linked to a massive gain of the CD44 + CD62L + phenotype, a feature of central memory T cells (T CM ; Fig. 1A -B). To determine whether peripheral T AIM cells observed in the Dot1L-KO setting originate intrathymically, as reported previously for IL-4 dependent innate memory T cells 3 , we compared RNA-Seq data from SP CD8 + thymocytes from KO and WT mice. cache = ./cache/cord-103517-1itisiup.txt txt = ./txt/cord-103517-1itisiup.txt === reduce.pl bib === id = cord-103606-5gbk6t6y author = Fettrow, Tyler title = Walking cadence affects the recruitment of the medial-lateral balance mechanisms date = 2019-06-03 pages = extension = .txt mime = text/plain words = 6106 sentences = 278 flesch = 50 summary = We limited our analysis to the time interval from the heel-strike triggering the stimulus to the end of the second double stance post-stimulus, which encompasses the three previously identified balance mechanisms of lateral ankle roll, foot placement shift and push-off modulation. We had expected the foot placement shift to be smaller in the Low condition, due to an increased and prolonged lateral ankle mechanism response, based on modeling results (Reimann et al., 2017) . The results indicate that all three previously identified balance mechanisms are used to respond to the perceived fall, but the majority of the balance response is shifted to the lateral ankle mechanism when walking with a low cadence. We also know that people with Parkinson's disease take shorter faster steps (Knutsson, 1972) , and although their overall gait speed is diminished, an increase in cadence may shift the majority of the balance response to the foot placement compared to age matched controls. cache = ./cache/cord-103606-5gbk6t6y.txt txt = ./txt/cord-103606-5gbk6t6y.txt === reduce.pl bib === id = cord-103542-mf721oa9 author = Mazhari, Ramin title = A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against P. vivax antigens in a multiplexed bead-based assay using Luminex® technology (Bio-Plex® 200 or MAGPIX®) date = 2020-08-10 pages = extension = .txt mime = text/plain words = 1326 sentences = 72 flesch = 52 summary = Multiplexed bead-based assays that use Luminex xMAP® technology have become popular for measuring antibodies against proteins of interest in many fields, including malaria and more recently SARS-CoV-2/COVID-19. Our external validation indicated that results generated in different laboratories using the same coupled beads are also highly comparable, particularly if a reference standard curve is used. To be able to measure all plasma 123 samples at the same dilution, we optimized all protein concentrations by generating a log-linear 124 standard curve with a positive control plasma pool from immune PNG donors (high responders to 125 Plasmodium antigens). Optimization of 374 a magnetic bead-based assay (MAGPIX((R))-Luminex) for immune surveillance of exposure to 375 malaria using multiple Plasmodium antigens and sera from different endemic settings Comparison of non-404 magnetic and magnetic beads multiplex assay for assessment of Plasmodium falciparum 405 antibodies cache = ./cache/cord-103542-mf721oa9.txt txt = ./txt/cord-103542-mf721oa9.txt === reduce.pl bib === id = cord-103648-g50g17ti author = Wang, Hao-Yuan title = Total synthesis and biological characterization of SR-A3, a ternatin-related eEF1A inhibitor with enhanced cellular residence time date = 2020-10-08 pages = extension = .txt mime = text/plain words = 2175 sentences = 124 flesch = 48 summary = Ternatin and related cyclic peptides inhibit the elongation phase of protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A), a potential therapeutic vulnerability in cancer and viral infections. Based on our hypothesis that A3 is structurally related to the anti-adipogenic cyclic heptapeptide, ternatin, 9 we previously designed and synthesized "ternatin-4", which incorporates the dehydromethyl leucine (dhML) and pipecolic acid residues found in A3, yet lacks the b-hydroxy group attached to N-Me-Leu ( Figure 1 ). Similar to ternatin-4, SR-A3 potently inhibited cell proliferation and protein synthesis by targeting eEF1A. Whereas protein synthesis rates partially recovered in cells treated with ternatin-4 or SS-A3 (~30% of DMSO control levels, 24 h post-washout), transient exposure of cells to SR-A3 resulted in sustained inhibition (Figure 6a ). Rather, SR-A3 exhibits a dramatic increase in cellular residence time, as revealed by washout experiments followed by assessment of protein synthesis and cell proliferation rates. cache = ./cache/cord-103648-g50g17ti.txt txt = ./txt/cord-103648-g50g17ti.txt === reduce.pl bib === id = cord-103528-3tib5o1m author = Ahmed, Asad title = DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date = 2020-09-28 pages = extension = .txt mime = text/plain words = 3798 sentences = 242 flesch = 54 summary = title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity Here, we have incorporated Convolutional Neural Networks that find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies towards a diverse set of ligands. Initial raw data database created contained protein structures in PDB format, protein sequences in FASTA format, ligand in SDF format and binding affinity values of corresponding protein-ligand pairs for 5464 complexes. We propose a deep-learning based approach to predict ligand (eg., drug)-target binding affinity using only structures of target protein (PDB format) and ligand (SDF format) as inputs. We have trained two models to predict the binding affinity between protein and ligand in a given complex. We have constructed a novel dataset that represents a diverse set of ligands and using a novel deep learning based approach we have achieved significant improvement in prediction of binding affinity of protein-ligand complexes. cache = ./cache/cord-103528-3tib5o1m.txt txt = ./txt/cord-103528-3tib5o1m.txt === reduce.pl bib === id = cord-103688-n7hzpbyf author = Wang, Lina title = VirusDIP: Virus Data Integration Platform date = 2020-06-09 pages = extension = .txt mime = text/plain words = 1286 sentences = 81 flesch = 47 summary = Results To facilitate virus research and promote the global sharing of virus data, we present here VirusDIP, a one-stop service platform for archive, integration, access, analysis of virus data. It accepts the submission of viral sequence data from all over the world and currently integrates data resources from the National GeneBank Database (CNGBdb), Global initiative on sharing all influenza data (GISAID), and National Center for Biotechnology Information (NCBI). Moreover, based on the comprehensive data resources, BLAST sequence alignment tool and multi-party security computing tools are deployed for multi-sequence alignment, phylogenetic tree building and global trusted sharing. For data compatibility, the virus data standard integrates the virus and pathogen sample data standard of The International Nucleotide Sequence Database Collaboration (INSDC) (Karsch-Mizrachi et al., 2018) , the hCoV-19 data standard of GISAID, and the sample data standard of COVID-19 Genomics UK (COG-UK) Consortium. VirusDIP is committed to building a comprehensive virus data platform for archive, integration, access, and analysis. cache = ./cache/cord-103688-n7hzpbyf.txt txt = ./txt/cord-103688-n7hzpbyf.txt === reduce.pl bib === id = cord-103580-6rf1xs0d author = Arokiaraj, Mark Christopher title = A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate date = 2020-05-15 pages = extension = .txt mime = text/plain words = 3669 sentences = 253 flesch = 44 summary = In this study, a novel method of immune-modulation to modify the endothelial function was studied to modulate the features of the endothelial cells, and thereby to reduce coronary artery disease and other disorders modulated by endothelium. Conclusion There is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using streptococcus pyogenes and its lysates. The study was performed in search of novel applications of streptococcus pyogenes in regulating immune functions, and its related effects on cardiovascular and its pleiotropic functions. When the cells were treated with streptococcus pyogenes' lysate, the levels of BLC -the B lymphocyte chemoattractant protein (CXCL13) was increased. 72 The heat map analysis shows a significant change in more proteins, and thereby it is possible to infer that streptococcus has a role in immune regulation. 78 Our study also reflects the immune regulation changes due to streptococcus pyogenes as well as by its lysate. cache = ./cache/cord-103580-6rf1xs0d.txt txt = ./txt/cord-103580-6rf1xs0d.txt === reduce.pl bib === id = cord-103568-zesg4atp author = Iacullo, Carly title = Non-selective inhibition of the motor system following unexpected and expected infrequent events date = 2020-03-26 pages = extension = .txt mime = text/plain words = 5559 sentences = 272 flesch = 44 summary = Consequently, in line with the proposal that unexpected sensory events lead to an automatic recruitment of the brain's reactive inhibition circuity even when stopping is not explicitly required (i.e., in the absence of proactive control), such events do indeed also produce non-selective suppression of CSE (Wessel & Aron, 2013) . Therefore, the goal of the current study was to investigate whether expected infrequent events can produce reactive motor inhibition, as indexed by non-selective CSE suppression. Using single-pulse TMS combined with EMG of task-unrelated hand muscles while participants performed forced-choice reaction time tasks with their feet, we found that infrequent expected sounds are indeed followed by a non-selective suppression of task-unrelated motor effectors. The latter finding replicates our previous report of non-selective CSE suppression in a verbal reaction time task when unexpected sounds were presented prior to the imperative stimulus (Wessel & Aron, 2013) . cache = ./cache/cord-103568-zesg4atp.txt txt = ./txt/cord-103568-zesg4atp.txt === reduce.pl bib === id = cord-103592-lkngp2u6 author = Bachmaier, Kurt title = Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date = 2020-07-02 pages = extension = .txt mime = text/plain words = 6316 sentences = 336 flesch = 47 summary = Using cecal ligation and puncture (CLP), a reproducible and clinically relevant mouse model of polymicrobial infection that causes ALI, we found that in naïve control mice after 2 sequential i.v. injections of ANP only ~4% of lung PMN endocytosed ANP as evidenced by ANP-specific fluorescence ( Figure 1B) . Importantly, we found that CCR1 receptor cell surface expression, consistent with the mRNA data, was significantly greater on lung ANP high PMN than in ANP low PMN before and 3h, 6h, and 12h after LPS stimulation ( Figure 3B ). We observed that nitrotyrosine-specific staining in inflammatory and parenchymal cells was significantly reduced in lungs and livers of mice treated with PANP when compared to ANP-treated controls ( Figure 6D ,E). Measuring a markers of overall cell damage, lactic dehydrogenase (LDH) (34) , revealed that the polymicrobial sepsis-induced increased serum activity of LDH was significantly reduced by PANP treatment when compared to ANP treated controls ( Figure 6G ). cache = ./cache/cord-103592-lkngp2u6.txt txt = ./txt/cord-103592-lkngp2u6.txt === reduce.pl bib === id = cord-103625-p55ew8w7 author = Ramana, Chilakamarti V. title = Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date = 2020-08-14 pages = extension = .txt mime = text/plain words = 3320 sentences = 217 flesch = 47 summary = Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. In this study, transcription factor profiling in interferon-mediated gene expression data sets and RT-PCR revealed that Egr-1 was rapidly induced by IFN-α/β and TLR ligands in multiple cell types. Respiratory pathogens including coronaviruses (SARS-CoV-1 and 2) and influenza viruses regulated the expression of Egr-1 in human lung cell lines and in lung biopsies and peripheral blood cells of COVID-19 patients, These studies suggest that the regulation of Egr-1 may play an important role in the antiviral response and inflammatory disease. cache = ./cache/cord-103625-p55ew8w7.txt txt = ./txt/cord-103625-p55ew8w7.txt === reduce.pl bib === id = cord-103523-46hn2249 author = Shaw, Dario R. title = Extracellular electron transfer-dependent anaerobic oxidation of ammonium by anammox bacteria date = 2019-11-26 pages = extension = .txt mime = text/plain words = 3315 sentences = 202 flesch = 52 summary = Here we show using complementary approaches that in the absence of NO2−, freshwater and marine anammox bacteria couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). However, it is still unknown whether anammox bacteria have EET 27 capability and can couple the oxidation of NH4 + with transfer of electrons to carbon-based 28 insoluble extracellular electron acceptors. However, it is still unknown whether anammox bacteria have EET 27 capability and can couple the oxidation of NH4 + with transfer of electrons to carbon-based 28 insoluble extracellular electron acceptors. Here we show using complementary approaches that in 29 the absence of NO2 -, freshwater and marine anammox bacteria couple the oxidation of NH4 + with 30 transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene 31 oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). cache = ./cache/cord-103523-46hn2249.txt txt = ./txt/cord-103523-46hn2249.txt === reduce.pl bib === id = cord-103714-06hhlma3 author = Miller, Mariël title = Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms date = 2020-06-04 pages = extension = .txt mime = text/plain words = 2440 sentences = 146 flesch = 51 summary = In this study, an in vitro assessment was performed to determine the potential efficacy of a unique first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. Confocal imaging and staining indicated that CZ-01179 was 357 highly effective against well-established biofilms that were exposed to the formulated gel, 358 whereas clinical products had limited efficacy (Fig 5) . Outcomes indicated that of the clinical standards of care, gentamicin was most effective 366 against both monomicrobial and polymicrobial biofilms of MRSA and of P. CZ-01179 gels were more efficacious at 415 eradicating biofilms in all other cases when compared to the standard of care topicals in the 416 collagen tests (Fig. 6) . cache = ./cache/cord-103714-06hhlma3.txt txt = ./txt/cord-103714-06hhlma3.txt === reduce.pl bib === id = cord-103652-yjl7uj2h author = Vickaryous, Nicola title = Remote testing of vitamin D levels across the UK MS population – a case control study date = 2020-10-16 pages = extension = .txt mime = text/plain words = 3259 sentences = 183 flesch = 52 summary = Data including baseline serum 25(OH)D levels, vitamin D supplementation (yes/no; no dose information available), oily fish consumption, time spent outdoors and UV sun protection usage were analysed. 72% (276/386) of the MS participants from the biological sampling group reported taking vitamin D supplements compared to 26% (79/305) of controls (p<0.001; Table 2 ). A lower proportion of people with MS took vitamin D supplementation at UKBB enrolment than in our current study, however they were still more likely to do so than the matched controls (14% vs 6%, p<0.001) (Supplementary table 5 ). Not only were MS participants more likely to take vitamin D supplements, but they also took them at higher doses, such that people with MS in the UK now have overall higher serum 25(OH)D levels than controls. Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study cache = ./cache/cord-103652-yjl7uj2h.txt txt = ./txt/cord-103652-yjl7uj2h.txt === reduce.pl bib === id = cord-103638-n5kpvsvg author = Nguyen, Long T. title = Enhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection date = 2020-04-14 pages = extension = .txt mime = text/plain words = 5357 sentences = 388 flesch = 60 summary = By extending the 3'or 5'-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discovered a new self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs were incorporated in a paper-based lateral flow assay that could detect the target with up to 23-fold higher sensitivity within 40-60 minutes. However, the ENHANCE showed 5.4-fold and 3.4-fold and higher trans-cleavage activity compared to the wild-type crRNA for targeting the methylated dsDNA and ssDNA, respectively (Fig. 3e, Supplementary Fig. 20a) . While no clinical samples were tested, the results indicated the 3'DNA7-modified crRNA consistently demonstrated higher sensitivity for detecting CoV-2 dsDNA within 30 minutes as compared to the wild-type crCoV-2 ( Supplementary Figs. cache = ./cache/cord-103638-n5kpvsvg.txt txt = ./txt/cord-103638-n5kpvsvg.txt === reduce.pl bib === id = cord-103739-mmkrwj8t author = Snijder, Eric J. title = A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis date = 2020-03-24 pages = extension = .txt mime = text/plain words = 3808 sentences = 223 flesch = 48 summary = Metabolic labelling of newly-synthesized viral RNA followed by quantitative EM autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs MERS-CoV and SARS-CoV, and the gamma-CoV infectious bronchitis virus. In infected cells, the CoV RNA-23 synthesizing machinery associates with modified endoplasmic reticulum membranes that are 24 transformed into the viral replication organelle (RO). In infected cells, the CoV RNA-23 synthesizing machinery associates with modified endoplasmic reticulum membranes that are 24 transformed into the viral replication organelle (RO). 106 double-membrane spherules (DMSs) 107 We first set out to analyse the ultrastructure of MERS-CoV-infected Huh7 cells under sample 108 preparation conditions favourable for autoradiography (see Materials and Methods) (Fig 1, S1 109 Video). Association of polioviral proteins of the P2 89 genomic region with the viral replication complex and virus-induced membrane synthesis as 90 visualized by electron microscopic immunocytochemistry and autoradiography cache = ./cache/cord-103739-mmkrwj8t.txt txt = ./txt/cord-103739-mmkrwj8t.txt === reduce.pl bib === id = cord-103674-pmbpx162 author = Kalaycı, Salih title = The Linkage among Sea Transportation, Trade Liberalization and Industrial Development in the context of Carbon Dioxide Emissions: An Empirical Investigation from China date = 2020-07-13 pages = extension = .txt mime = text/plain words = 4523 sentences = 226 flesch = 45 summary = According to results of FMOLS, DOLS and CCR models there is a long-term stable relationship between sea transportation, trade liberalization, industrial development and carbon dioxide emissions which is proved empirically. In this study, empirical results proved the impact of sea transportation, trade liberalization and industrial development on carbon dioxide emissions for China from 1980 to 2013. The long-run relationship between carbon dioxide emissions 2 sea transportation trade liberalization and industrial development is investigated through f bounds test which is considered the zero hypothesis. Findings from FMOLS, DOLS and CCR models indicate that maritime transport, trade liberalization and industrial development are the determinants of long-term carbon emissions, just as in the results of the ARDL model. Findings from FMOLS, DOLS and CCR models indicate that maritime transport, trade liberalization and industrial development are the determinants of long-term carbon emissions, just as in the results of the ARDL model. cache = ./cache/cord-103674-pmbpx162.txt txt = ./txt/cord-103674-pmbpx162.txt === reduce.pl bib === id = cord-103781-bycskjtr author = Mönke, Gregor title = Optimal time frequency analysis for biological data - pyBOAT date = 2020-06-04 pages = extension = .txt mime = text/plain words = 7386 sentences = 451 flesch = 54 summary = With this challenge in mind, we have developed pyBOAT, a Python-based fully automatic stand-alone software that integrates multiple steps of non-stationary oscillatory time series analysis into an easy-to-use graphical user interface. Our approach integrates data-visualization, optimized sinc-filter detrending, amplitude envelope removal and a subsequent continuous-wavelet based time-frequency analysis. Computational methods that enable analysis of periods, amplitudes and phases of rhythmic time series data have been essential to unravel function and design principles of biological clocks (Lauschke et al. This allows to use a straightforward numerical method to estimate a lter response | w(ω)| 2 , i.e. applying the smoothing operation to simulated white noise and time averaging the Wavelet spectra. Continuous wavelet analysis allows to reveal non-stationary period, amplitude and phase dynamics and to identify multiple frequency components across dierent scales within a single oscillatory signal (Leise [2013] , Leise et al. cache = ./cache/cord-103781-bycskjtr.txt txt = ./txt/cord-103781-bycskjtr.txt === reduce.pl bib === id = cord-103735-nil1vv6h author = Alfano, Niccolo title = Non-invasive surveys of mammalian viruses using environmental DNA date = 2020-03-29 pages = extension = .txt mime = text/plain words = 5829 sentences = 373 flesch = 53 summary = Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. In filtered water and sediment samples collected from the same waterhole, only one virus per sample was generally identified and in one location (WM20 and SM20) contigs from different viral families were isolated based on sample type. We provide evidence that environmental and invertebrate-derived DNA samples including waterhole water, sediment and wild haematophagous terrestrial leeches can be used to survey known and unknown viruses. cache = ./cache/cord-103735-nil1vv6h.txt txt = ./txt/cord-103735-nil1vv6h.txt === reduce.pl bib === id = cord-103597-mt0h06y3 author = Muller, Alana title = Neurophysiological Correlates of the Dunning-Kruger Effect date = 2020-05-20 pages = extension = .txt mime = text/plain words = 14179 sentences = 640 flesch = 45 summary = Between-group EEG differences were evident between over-estimators and under-estimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators from 400-600 ms, whereas 'old-new' memory ERP effects revealed a late parietal component (LPC) associated with recollection-based processing from 600-900 ms for under-estimators that was not evident for over-estimators. Results Between-group EEG differences were evident between over-estimators and underestimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators from 400-600 ms, whereas 'oldnew' memory ERP effects revealed a late parietal component (LPC) associated with recollection-based processing from 600-900 ms for under-estimators that was not evident for over-estimators. One suggestion from these results is that the frontal effect at 400-600 ms may be characteristic of the FN400 ERP effect related to familiarity-based processing, in that over-estimators may be relying on the less-specific memory process of familiarity or intuitions of increased fluency to guide making their metacognitive judgments, instead of relying upon the more distinct recollection-related processes (Yonelinas et al., 2010 ) that evidently appears to be supporting the people who were under-estimating their performance relative to the group (Figure 7 ). cache = ./cache/cord-103597-mt0h06y3.txt txt = ./txt/cord-103597-mt0h06y3.txt === reduce.pl bib === id = cord-103703-t03r6ny8 author = Nguyen-Tu, Marie-Sophie title = Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice date = 2020-05-20 pages = extension = .txt mime = text/plain words = 6230 sentences = 300 flesch = 50 summary = title: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice Mice with biallelic Tcf7l2 deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reduced in vivo glucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Therefore, alterations in pancreatic beta cell function observed ex vivo in the absence of TCF7L2 in adipocyte have no impact on whole body glucose-stimulated insulin secretion. A striking finding in the present study is that TCF7L2 is required in adipose tissue for normal incretin production and insulin secretion: we reveal that decreased Tcf7l2 expression in mature adipocytes leads to lowered circulating levels of GLP-1 and GIP ( Fig.4a and b) . cache = ./cache/cord-103703-t03r6ny8.txt txt = ./txt/cord-103703-t03r6ny8.txt === reduce.pl bib === id = cord-103733-blam1f4c author = Levade, Inès title = Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study date = 2020-06-24 pages = extension = .txt mime = text/plain words = 2663 sentences = 145 flesch = 41 summary = title: Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera. Conclusion Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera. SUMMARY Cholera infection and disease severity can be predicted using metagenomic sequencing of the gut microbiome pre-infection in a prospective cohort, and suggests potentially protective bacterial species and genes. Our metagenomic analysis yielded improved 85 outcome predictions compared to 16S rRNA sequencing, and identified bacterial genes 86 associated with remaining uninfected after exposure to V. Applied to the Midani 230 2018 cohort, this model predicted outcomes significantly better than random (shuffled labels) 231 using species, strains or pathway data, but not gene families ( Table 1 ; see Table S3 for p-232 values). cache = ./cache/cord-103733-blam1f4c.txt txt = ./txt/cord-103733-blam1f4c.txt === reduce.pl bib === id = cord-103773-1b961lfz author = Kurokawa, Shunji title = In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model date = 2020-05-29 pages = extension = .txt mime = text/plain words = 2917 sentences = 170 flesch = 39 summary = title: In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries then evaluated graft patency, ECM preservation and recellularization. Scanning electron microscopy on luminal surface of implanted grafts exhibited cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Elastica van Gieson staining and Sirius red staining exhibited a fair preservation of elastin layer (internal elastic lamina), tunica media consisted of collagen fibers and stratified elastin layers in HHP-decellularized grafts, and recellularization at 4 weeks after implantation, respectively (Fig. 4B) . The luminal surface of decellularized bovine graft implanted at porcine carotid artery for 4 weeks showed endothelium with cobblestone-like appearance by fair recellularization similar with those in bovine and porcine native arteries (recipient animal) (Fig. 5A , C, D). cache = ./cache/cord-103773-1b961lfz.txt txt = ./txt/cord-103773-1b961lfz.txt === reduce.pl bib === id = cord-103715-53v1qoyc author = Bauman, Neda title = Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts date = 2020-05-21 pages = extension = .txt mime = text/plain words = 1028 sentences = 62 flesch = 53 summary = title: Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts A novel approach to analyze the structure of in vivo-derived tissue cysts may be the increasingly used computational image analysis. gondii cysts by morphological, particle, and fractal analysis, as well as to determine if and how it is impacted by parasite strain, cyst age, and host factors. The parameters of interest included diameter, circularity, relative particle count (RPC), fractal dimension (FD), lacunarity, and packing density (PD). Cysts were transferred to black background images for subsequent particle analysis. In that manner, all of the cyst cross-section images were subjected to an 148 automated processing and the obtained particle numbers, N p , were expected to be proportional to the Fig 2C. Novel approaches reveal that Toxoplasma 357 gondii bradyzoites within tissue cysts are dynamic and replicating entities in vivo Vet S2 Data -Fractal dimension and lacunarity of tissue cysts (n=31) cache = ./cache/cord-103715-53v1qoyc.txt txt = ./txt/cord-103715-53v1qoyc.txt === reduce.pl bib === id = cord-103654-k02z72gb author = Gamboa Arana, Olga Lucia title = Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex date = 2020-06-15 pages = extension = .txt mime = text/plain words = 5839 sentences = 241 flesch = 38 summary = Studies of motion perception are particularly well-suited for exploring mechanisms of TMS due to the superficial location of motion sensitive cortex and its well-characterized spatiotemporal progression of electroencephalographic (EEG) activation described by the P1/N2/P3 Visual Evoked Potential (VEP) complex. For this purpose, we used a three-visit study design consisting of an initial dose-finding session to derive individualized motion coherence thresholds and stimulation parameters based on the onset of the N2 VEP component ("N2-Onset"), followed by two dose-testing sessions during which spTMS was delivered according to the spatial, temporal, and intensity parameters derived from the first session. The overall goal was to map the behavioral and evoked EEG dose-response functions within the constructs of individualized spatiotemporal targeting with the expectation that spTMS delivered at the onset of the N2 component would disrupt motion processes in the brain and lead to monotonic effects across different stimulation intensities. cache = ./cache/cord-103654-k02z72gb.txt txt = ./txt/cord-103654-k02z72gb.txt === reduce.pl bib === id = cord-103872-yzqic5vt author = Liu, Zhijin title = Global view on virus infection in non-human primates and implication for public health and wildlife conservation date = 2020-05-13 pages = extension = .txt mime = text/plain words = 1310 sentences = 81 flesch = 51 summary = Research has revealed that SARS-CoV-2 and other coronaviruses have been transmitted from animals to humans and vice versa, and across animal species, and hence, attracted public attention concerning host-virus interactions and transmission ways. We suggest epidemiological investigations in NHPs, specifically in Old World monkeys with close contact to humans, and other effective measures to prevent this potential circular transmission. First, we generated a summary statistics of worldwide reported VI-NHPs. We then 61 identified and predicted NHP species with a high risk of virus transmission from humans and 62 predicted geographic locations where disease outbreaks are likely to occur. Since centrality in primate-virus networks could assess the potential for the 72 circulation of viruses among NHPs and humans, we estimated the centrality using four metrics: 73 strength degree centrality, eigenvector centrality, betweenness centrality, and closeness centrality 74 implemented in the R package "igraph" and UCINET 6. Centrality in primate-parasite networks 225 reveals the potential for the transmission of emerging infectious diseases to humans cache = ./cache/cord-103872-yzqic5vt.txt txt = ./txt/cord-103872-yzqic5vt.txt === reduce.pl bib === id = cord-103812-ls6zgipi author = Norris, Rachael P. title = Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study date = 2020-06-30 pages = extension = .txt mime = text/plain words = 4803 sentences = 296 flesch = 55 summary = Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Gap junction internalization can also be considered to be a form of trogocytosis (Joly and Hudriser, 2003) in which a portion of the plasma membrane and cytosol of the neighboring cell is transferred to the engulfing cell (See Fig. 1A ). Serial sections were then imaged to obtain threedimensional information; this distinguished between internalized connexosomes and gap junctions in the process of invagination. In 7 of the 56 modified connexosomes, a patch of unlabeled outer membrane bulged outward from a labeled inner membrane ( suggesting that different types of vesicles were involved. Five serial sections through a modified connexosome containing several internal vesicles labeled with Cx43. cache = ./cache/cord-103812-ls6zgipi.txt txt = ./txt/cord-103812-ls6zgipi.txt === reduce.pl bib === id = cord-103757-fed21fhu author = McPherson, Malinda J. title = Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory date = 2020-10-15 pages = extension = .txt mime = text/plain words = 13309 sentences = 653 flesch = 48 summary = The similarity in performance between harmonic and inharmonic tones without a delay provides circumstantial evidence that listeners are computing changes in the same way for both types of stimuli, presumably using a representation of the spectrum in both cases. We examined the relationship between pitch perception and memory by measuring the discrimination of harmonic and inharmonic sounds with and without a time delay between stimuli. The results provide evidence for two distinct mechanisms for pitch discrimination, reveal the constraints that determine when they are used, and demonstrate a form of abstraction within the auditory system whereby the representations of memory differ in format from those used for rapid on-line judgments about sounds. We found consistent overall pitch discrimination advantages for musicians compared to non-musicians ( Supplementary Figures 1-3 ), but found no evidence that this benefit was specific to f0 representations: musicianship did not interact with the effects of inharmonicity or inter-stimulus delay. cache = ./cache/cord-103757-fed21fhu.txt txt = ./txt/cord-103757-fed21fhu.txt === reduce.pl bib === id = cord-103830-pu6v53oy author = Pichon, Fabien title = Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips date = 2020-05-10 pages = extension = .txt mime = text/plain words = 5439 sentences = 225 flesch = 47 summary = In the present study, we evaluated the use of the Infinium 450K and Infinium EPIC BeadChips for genome-wide DNA methylation analyses in samples from Chlorocebus sabaeus and Macaca mulatta and conducted an in-depth analysis of the available probes for these two old world monkey genomes. We provide for each species and each microarray a list of annotated probes that can be used by the scientific community for genome-wide DNA methylation studies in Chlorocebus sabaeus or Macaca mulatta. We then mapped all the 50 bp probe sequences targeting CpG positions in the human genome from the Infinium 450K and EPIC arrays to Chlorocebus sabaeus (CS) and Macaca mulatta (MM) genomes, consecutively, using Bowtie [39], allowing only a unique position on the respective genome and up to 3 mismatches. cache = ./cache/cord-103830-pu6v53oy.txt txt = ./txt/cord-103830-pu6v53oy.txt === reduce.pl bib === id = cord-103802-mygo3qx0 author = Li, Yanpeng title = Multiple known and a novel parvovirus associated with an outbreak of feline diarrhea and vomiting date = 2020-03-25 pages = extension = .txt mime = text/plain words = 1779 sentences = 133 flesch = 53 summary = title: Multiple known and a novel parvovirus associated with an outbreak of feline diarrhea and vomiting An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and different feline bocaviruses shed by 9/17 cats. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. Shelter 2 a total of 5 individual cats and a sample pool (mixed feces from 3 cats) were Using metagenomics, we found FeBoV1, 2, and 3 and a novel chaphamaparvovirus we named 311 fechavirus in a large fraction of fecal samples and fechavirus in all vomit samples from sick cats 312 in a multi-facility outbreak. Feline Virome-A Review of 409 Novel Enteric Viruses Detected in Cats Feline fecal virome reveals novel and prevalent enteric viruses cache = ./cache/cord-103802-mygo3qx0.txt txt = ./txt/cord-103802-mygo3qx0.txt === reduce.pl bib === id = cord-103709-86hv27vh author = Zhang, Dong Yan title = Prefusion spike protein stabilization through computational mutagenesis date = 2020-06-19 pages = extension = .txt mime = text/plain words = 3243 sentences = 184 flesch = 53 summary = The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We subject the selected residues to computational redesign using Eris to find the stabilizing mutations by calculating the change in free energy ∆∆ = ∆ − ∆ , where ∆ and ∆ are the free energies of the mutant protein and wild type proteins correspondingly. After the designation of the mutation sites, the pipeline utilizes Eris to determine the changes in free energies of the mutants. We analyze the conservation score, RMSF, and SASA of residues in the spike protein through the pipeline. Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes cache = ./cache/cord-103709-86hv27vh.txt txt = ./txt/cord-103709-86hv27vh.txt === reduce.pl bib === id = cord-103869-ii6qi1bp author = Yang, Liu title = Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs date = 2020-09-28 pages = extension = .txt mime = text/plain words = 7435 sentences = 386 flesch = 51 summary = Current methods based on structural comparison or alignment of protein pockets have identified many well-defined 3D motifs that are conserved across different protein pockets and widely used for protein function annotation, pockets classification and ligand-binding prediction (Gao and Skolnick, 2013; Hoffmann et al., 2010; Hwang et al., 2017; Pires et al., 2013; Pu et al., 2019; Yeturu and Chandra, 2008) . To systematically identify and evaluate 3D binding motifs at FG level, we developed AFTME, an alignment-free method that automatically maps functional atoms to different FGs from a set of protein pockets binding the same ligand using two-dimensional clustering approach. We have developed AFTME, a computational method to dissect protein pockets binding a specific ligand into sectors that interact with different functional groups (FGs). The basic assumption of this method is simple: if conserved binding pattern for a specific FG exists, the pattern-forming atoms should be spatially proximal to the corresponding FG and frequently co-appear, thus can be detected through clustering analysis of functional atoms from diverse protein pockets binding the same ligand. cache = ./cache/cord-103869-ii6qi1bp.txt txt = ./txt/cord-103869-ii6qi1bp.txt === reduce.pl bib === id = cord-103813-w2sb6h94 author = Schumacher, Garrett J. title = Genetic information insecurity as state of the art date = 2020-07-10 pages = extension = .txt mime = text/plain words = 6459 sentences = 358 flesch = 35 summary = Therefore, human genetic information is a uniquely confidential form of data that requires increased security controls and scrutiny. Sensitive genetic information, which includes both biological material and digital genetic data, is the primary asset of concern, and associated assets, such as metadata, electronic health records and intellectual property, are also vulnerable within this ecosystem. ❖ Private Sensitive Genetic Information can be expected to cause a moderate level of risk to a nation, ethnic group, individual, or stakeholder if it is disclosed, modified, or destroyed without authorization. The genetic information ecosystem is a distributed cyber-physical system containing numerous stakeholders (Supplementary Material, Appendix 1), personnel, and devices for computing and networking purposes. Genetic information security is a shared responsibility between sequencing laboratories and device vendors, as well as all other involved stakeholders. Examples include biorepositories, DNA sequencing laboratories, researchers, cloud and other service providers, and supply chain entities responsible for devices, software and materials. cache = ./cache/cord-103813-w2sb6h94.txt txt = ./txt/cord-103813-w2sb6h94.txt === reduce.pl bib === id = cord-103770-4svaq0at author = Ogrodzinski, Martin P. title = Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes date = 2019-10-07 pages = extension = .txt mime = text/plain words = 668 sentences = 49 flesch = 46 summary = title: Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes Here, we used tumor-derived cell lines derived from the MMTV-Myc mouse model to investigate metabolic pathways that are differentially utilized between two subtypes of breast cancer. To determine metabolic profiles of histologically distinct mouse mammary tumor subtypes, 84 polar metabolites were extracted from tumor-derived cell lines and quantitated using LC-MS/MS. We found metabolites involved in several central carbon metabolic pathways to be differentially 86 abundant between EMT and papillary tumor-derived cell lines (Figure 2 ). In the EMT subtype, both oxidized and reduced forms of glutathione, a key metabolite in 88 redox homeostasis, are elevated ( Figure 2B ). Metabolites 92 increased in the papillary subtype include fructose bisphosphate (FBP; glycolysis); acetyl-CoA indicating relative metabolite differences between EMT and papillary tumor derived cell lines. (B) Representative bar graphs of metabolites with statistically significant differences between EMT and papillary subtypes. cache = ./cache/cord-103770-4svaq0at.txt txt = ./txt/cord-103770-4svaq0at.txt === reduce.pl bib === id = cord-103864-4kec8re4 author = Miao, Zhen title = Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets date = 2020-06-04 pages = extension = .txt mime = text/plain words = 1819 sentences = 113 flesch = 39 summary = Here, we profiled open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms. Here, we reasoned that 474 single cell accessible chromatin information could be extremely useful to identify the cell type-475 specific enhancer regions and thereby the target cell type for the GWAS hits, however, such maps 476 have not been generated for the human kidney. 539 540 By performing massively parallel single cell profiling of chromatin state, we were able to define 541 the key regulatory logic for each kidney cell type by investigating cis-regulatory elements and TF-542 target gene interaction. 548 549 We also observed that the single cell open chromatin atlas was able to define more distinct cell 550 types even in the developing kidney compared to scRNA-seq analysis. cache = ./cache/cord-103864-4kec8re4.txt txt = ./txt/cord-103864-4kec8re4.txt === reduce.pl bib === id = cord-103876-2rg2qtdq author = Watkins, Laura C. title = Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics date = 2020-06-20 pages = extension = .txt mime = text/plain words = 5528 sentences = 249 flesch = 47 summary = In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. Along with an earlier qualitative MD simulation study that guided the design of the spiro-adamantyl amine inhibitors, 41 the crystallographic analysis provided potential insights into the mechanism of inhibition, suggesting that the backbone carbonyls of pore-lining residues act as physiochemical chameleons, able to engage in both hydrophobic and hydrophilic interactions, and that the drug is tilted off the channel's axis and interacts with waters in the Ala30 layer. Most recently, we further analyzed the MS-RMD simulations to explore the detailed interactions between the hydrated excess proton and the channel and found that the proton dynamically, as a function of its position, alters several properties of the protein and pore waters, including the hydrogen-bonding network and the protein structure. cache = ./cache/cord-103876-2rg2qtdq.txt txt = ./txt/cord-103876-2rg2qtdq.txt === reduce.pl bib === id = cord-103924-mhgnqi80 author = Shin, Donghyuk title = Novel class of OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection date = 2020-04-28 pages = extension = .txt mime = text/plain words = 2096 sentences = 220 flesch = 67 summary = MS analysis of catalytically inactive LotB and LotC identified different categories of host-substrates for these two related DUBs. Together, our results provide new structural insights of bacterial OTU deubiquitinases and indicate distinct roles of bacterial deubiquitinases in host-pathogen interactions. Whereas the overall fold of the 174 catalytic core of LotB and LotC resembles that of other OTU-deubiquitinases, both showed clear 175 differences in the helical arm region, which has been shown to interact with ubiquitin and it serves 176 as an S1 binding site (Mevissen et al., 2013) . To address this, we performed ubiquitin 192 docking into both LotB and LotC, followed by molecular dynamics (MD) simulations for 600 ns 193 ( Fig. 4aTo gain better insights into the physiological roles of LotB and LotC, we decided to identify their 216 interacting proteins or substrates. cache = ./cache/cord-103924-mhgnqi80.txt txt = ./txt/cord-103924-mhgnqi80.txt === reduce.pl bib === id = cord-103946-c5i8btp7 author = Li, Maohua title = Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo date = 2020-07-01 pages = extension = .txt mime = text/plain words = 4380 sentences = 216 flesch = 51 summary = Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Based on the structural information acquired from different antibodies in Protein data bank (e.g., PDB ID: 1IGT), we hypothesized that an insertion of a short but very flexible sequence in the hinge region or somewhere upstream of the glycosylation site of N297 may cut off the stress transmission signal between the Fv and Fc domain. Clearly, the insertion of GGGS between G237 and G238 of human IgG1 heavy chain showed no significant negative impact on antibody's affinity and inhibitory activity. Our data demonstrated that the insertion of GGGS in the hinge regions of human IgG1 could abolish their ADCC activities completely without concering negative impact on antibody affinities, inhibitory activities, expression levels, stabilities or immunogenicity. For those well-known antibody drugs, such as Genentech's aglycosylated anti-PD-L1 Atezolizumab, we demonstrated that inserting GGGS in the hinge regions of human IgG1 Fc could remove the ADCC activities completely. cache = ./cache/cord-103946-c5i8btp7.txt txt = ./txt/cord-103946-c5i8btp7.txt === reduce.pl bib === id = cord-103788-sxw4l9tt author = Talbot, Steven R. title = One score to rule them all: severity assessment in laboratory mice date = 2020-06-24 pages = extension = .txt mime = text/plain words = 5994 sentences = 345 flesch = 56 summary = Body weight, the Mouse Grimace Scale score, burrowing behavior, and the telemetry-derived parameters heart rate, heart rate variability, temperature, and general activity were used to investigate the quality of indicating severity during postoperative recovery. In addition to the data for 184 building the RELSA reference set from TM-implanted mice, we evaluated RELSA performance as a 185 tool for severity comparisons between models by including data from three additional animal studies 186 (colitis, stress, sepsis). To exclude selection bias, we calculated the models' severity level with a 285 full set of available variables: body weight change, burrowing behavior, MGS score and telemetry-286 derived parameters including hr, hrv and temperature. A RELSA score of 1 means that all contributing variables for a 584 test animal reached the same values as the largest observed deviations in the reference set with the 585 defined level of severity (here, "moderate"). cache = ./cache/cord-103788-sxw4l9tt.txt txt = ./txt/cord-103788-sxw4l9tt.txt === reduce.pl bib === id = cord-103914-ppgx7mci author = Maughan, Elizabeth F. title = Cell-intrinsic differences between human airway epithelial cells from children and adults date = 2020-04-20 pages = extension = .txt mime = text/plain words = 8186 sentences = 419 flesch = 47 summary = Here, we perform bulk RNA sequencing studies in laser-capture microdissected whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We found no significant differences in the proportion of cells in these three cellular compartments in paediatric and adult biopsies either by immunohistochemistry ( Figure 1A /1B), or by assessing basal, mucosecretory or ciliated cellassociated gene expression (Table S2 ) in bulk RNA sequencing in which we had laser-capture microdissected the whole epithelium ( Figure 1C ; Figure S1 ). Analysing this laser-capture microdissected whole epithelium RNA sequencing dataset using DESeq2 (Love et al., 2014) with a false discovery rate (FDR) of 1% and log2 fold change threshold of 1.2, we identified 37 genes with significant differential expression between paediatric and adult donors of which 17 were upregulated in adults and 20 were expressed at higher levels in children ( Figure 2A ; Table S3 ). cache = ./cache/cord-103914-ppgx7mci.txt txt = ./txt/cord-103914-ppgx7mci.txt === reduce.pl bib === id = cord-103888-ggm29vrz author = Nova, Nicole title = Susceptible host availability modulates climate effects on dengue dynamics date = 2020-10-19 pages = extension = .txt mime = text/plain words = 1538 sentences = 86 flesch = 44 summary = By analyzing incidence data, estimated susceptible population size, and climate data with methods based on nonlinear time series analysis (collectively referred to as empirical dynamic modeling), we identified drivers and their interactive effects on dengue dynamics in San Juan, Puerto Rico. By capturing mechanistic, nonlinear, and context-dependent effects of population susceptibility, temperature, and rainfall on dengue transmission empirically, our model improves forecast skill over recent, state-of-the-art models for dengue incidence. Scenario exploration with multivariate EDM allowed us to assess the effect of a 270 small change in temperature or rainfall on dengue incidence, across different states 271 of the system. Compared to 298 the other drivers, the converging cross-mapping skill of the temperature null 299 models were relatively high (Figures 3 and S8 As expected, EDM tests for putative causality in the nonsensical directions-304 incidence driving temperature or rainfall-were not significant (i.e., no convergence; Figure S7 , black lines). cache = ./cache/cord-103888-ggm29vrz.txt txt = ./txt/cord-103888-ggm29vrz.txt === reduce.pl bib === id = cord-103925-i73ymrov author = Hill, Chris H. title = Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus date = 2020-08-11 pages = extension = .txt mime = text/plain words = 11552 sentences = 550 flesch = 53 summary = Finally, we use metabolic labelling and ribosome profiling to study 2A-mediated frameshifting and translation of the TMEV genome at sub-codon resolution in infected cells. A meta-analysis of the inferred P site positions of ribosomes relative to host mRNA start and stop codons reveals that RPFs map to coding sequences with a triplet periodicity reflective of the length of a codon ( Figure S3D ). Moving on to look specifically at the frameshift site, a single-nucleotide resolution plot of reads mapping to this region reveals a peak on the SS mutant genome corresponding to a ribosome paused with the GUU codon of the slippery sequence in the P site ( Figure 5G , Figure S4C ). These read lengths were selected for analysis as potential "disome-protected fragments", and their density plotted on the viral genome at the inferred P site position of the upstream, colliding ribosome ( Figure 6C and D). cache = ./cache/cord-103925-i73ymrov.txt txt = ./txt/cord-103925-i73ymrov.txt === reduce.pl bib === id = cord-103853-ar09nzmw author = Wayment-Steele, Hannah K. title = RNA secondary structure packages ranked and improved by high-throughput experiments date = 2020-05-31 pages = extension = .txt mime = text/plain words = 4328 sentences = 201 flesch = 42 summary = 20 In this work, we evaluate the performance of commonly-used packages capable of making thermodynamic predictions in two tasks that have been crowdsourced on Eterna and are emerging as central to RNA characterization and design: 1) predicting chemical reactivity data through calculating probabilities that nucleotides are unpaired, and 2) predicting relative stabilities of multiple structural states that underlie the functions of riboswitch molecules, a task that involves predicting affinities of both small molecules and proteins of interest. We evaluated commonly used secondary structure modeling packages in their ability to make thermodynamic predictions on a compilation of large datasets of diverse synthetic molecules from Eterna, which we termed EternaBench ( Figure 1A ). We trained models with a variety of combinations of data types to explore interactions in multitask training (Table 1) and evaluated performance on held-out test sets for single-structure prediction accuracy, chemical mapping prediction accuracy, and riboswitch fold change prediction. cache = ./cache/cord-103853-ar09nzmw.txt txt = ./txt/cord-103853-ar09nzmw.txt === reduce.pl bib === id = cord-104008-luqvw0y8 author = Levinson, Julia title = Investigating the effectiveness of school health services delivered by a health provider: a systematic review of systematic reviews date = 2019-02-07 pages = extension = .txt mime = text/plain words = 6729 sentences = 337 flesch = 50 summary = Systematic reviews of intervention studies that evaluated school-based or school-linked 31 health services delivered by a health provider were included. Systematic reviews of intervention studies that evaluated school-based or school-linked 31 health services delivered by a health provider were included. Through a comprehensive literature search, the 71 overview aimed to identify health areas and specific school health service interventions that 72 have at least some evidence of effectiveness. Finally, 74 the overview aimed to identify the health areas and specific school health services 75 interventions for which no SRs were found, whether because the primary literature does not 76 exist or where there are primary studies but no SR has been conducted. It is difficult to determine overall effectiveness of school health services from this overview because the included SRs do not sufficiently cover the health areas most relevant for children and adolescents. cache = ./cache/cord-104008-luqvw0y8.txt txt = ./txt/cord-104008-luqvw0y8.txt === reduce.pl bib === id = cord-103940-a2cqw8kg author = Shi, Yuejun title = Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins date = 2020-06-09 pages = extension = .txt mime = text/plain words = 3207 sentences = 216 flesch = 63 summary = Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. In this study, 130 we selected SARS-CoV, SARS-CoV-2, and HCoV-229E as models, which adopt the 131 two RBD states, and evaluated and compared immune responses to the S trimers and 132 7 RBDs of these coronaviruses through immunological and bioinformatics approaches. 133 We also investigated the mechanism through which the HCoV-229E S trimer 134 produced effective nAbs. Finally, we provide possible vaccine strategies for alphaTo address this issue, we performed B-cell epitope predictions for the S trimers 152 and RBDs of alpha-CoV (HCoV-229E) and beta-CoVs (SARS-CoV and 153 SARS-CoV-2). Taken together, these results showed that the intact and stable S1 subunit of 240 HCoV-229E is a prerequisite for the production of effective nAbs. Furthermore, our experimental results show that RBD has a higher ability to bind 242 12 to the receptor hAPN (Fig. 4B) , which indicates that the characteristics of RBD itself 243 may lead to the generation of less neutralizing antibodies. cache = ./cache/cord-103940-a2cqw8kg.txt txt = ./txt/cord-103940-a2cqw8kg.txt === reduce.pl bib === id = cord-103892-v6gkubd4 author = Mäkinen, Janne J. title = The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date = 2020-07-01 pages = extension = .txt mime = text/plain words = 8442 sentences = 418 flesch = 51 summary = Overall, these data demonstrated that the enhanced or diminished capabilities of the variant RNAPs to utilize 2'dGTP in the SNA assays reflected, in qualitative terms, their capabilities to utilize all four 2'dNTPs. The role of the β'Arg425 in selectively promoting the binding of NTPs was easy to explain because the β'Arg425 interacts with the 2'OH of the NTP analogues in several RNAP structures (Supplementary Table 5 , Fig. 1c, 4a, b) . We further hypothesized and demonstrated by in silico docking experiments that the 3'OH could move to within the hydrogen bond distance of the β'Arg425 if the deoxyribose moiety adopted a 2'-endo conformation (Supplementary Fig. 8 To test this hypothesis in crystallo, we solved the X-ray crystal structure of the initially transcribing complexes containing T. Overall, the comparative analysis of RNAP structures with CMPCPP, 2'dCTP and 3'dCTP suggested that the β'Arg425 inhibited the incorporation of 2'dNTPs by interacting with their 3'OH group and favoring the 2'-endo conformation of the deoxyribose moiety. cache = ./cache/cord-103892-v6gkubd4.txt txt = ./txt/cord-103892-v6gkubd4.txt === reduce.pl bib === id = cord-103964-k6jnv87v author = Friedl, Jana title = More than just a ticket canceller: The mitochondrial processing peptidase matures complex precursor proteins at internal cleavage sites date = 2020-07-03 pages = extension = .txt mime = text/plain words = 2329 sentences = 150 flesch = 52 summary = title: More than just a ticket canceller: The mitochondrial processing peptidase matures complex precursor proteins at internal cleavage sites After import into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase MPP, giving rise to shorter mature proteins. Arg5,6 is synthesized as a polyprotein precursor that is imported into the mitochondrial matrix and subsequently separated into two distinct enzymes that function in arginine biogenesis. Our data suggest that, in addition to its role as "ticket canceller" for the removal of presequences, MPP exhibits a second, widely conserved activity as internal processing peptidase for complex mitochondrial precursor proteins. We conclude that Arg5,6 is imported into the mitochondrial matrix 104 via the presequence pathway and cleaved into separate polypeptides inside mitochondria. Incubation of radiolabeled Arg5,6 precursor protein with MPP resulted in the formation of smaller 124 fragments whose size perfectly matched those that were generated after import into isolated 125 mitochondria (Fig. 1E ). cache = ./cache/cord-103964-k6jnv87v.txt txt = ./txt/cord-103964-k6jnv87v.txt === reduce.pl bib === id = cord-104035-ykyr2gvl author = Ivanov, Mark V. title = Boosting the MS1-only proteomics with machine learning allows 2000 protein identifications in 5-minute proteome analysis date = 2020-10-29 pages = extension = .txt mime = text/plain words = 1844 sentences = 115 flesch = 43 summary = A number of methods and approaches to MS/MS-free proteome analysis have been proposed and widely explored starting from the early Accurate Mass and Tag (Time) method [21] [22] [23] [24] [25] to a recent truly (e.g., without employing tandem mass spectrometry at any step in the workflow) MS/MS-free realizations 26, 27 . 27 Because the method does not employ isolation and fragmentation steps, the time for peptide separation can be reduced significantly to few minutes and the number of MS1 spectra available for processing will only be limited by the acquisition rate of the mass analyzer operating at high mass resolution. Also, the method was upgraded and tested for processing MS1-only data obtained using high resolution mass spectrometry and the high-field asymmetric waveform ion mobility, FAIMS 35 , which was found increasingly applicable in proteomic research 36, 37 as it provides additional separation dimension for peptides at the front end of a mass spectrometer. cache = ./cache/cord-104035-ykyr2gvl.txt txt = ./txt/cord-104035-ykyr2gvl.txt === reduce.pl bib === id = cord-104122-klvx927g author = Tayfuroglu, Omer title = An Accurate Free Energy Method for Solvation of Organic Compounds and Binding to Proteins date = 2020-05-28 pages = extension = .txt mime = text/plain words = 2408 sentences = 160 flesch = 46 summary = The method is adopted from ANI-1ccx neural network potentials (Machine Learning) for the Atomic Simulation Environment (ASE) and predicts the single point energies at the accuracy of CCSD(T)/CBS level for the entire configurational space that is sampled by Molecular Dynamics (MD) simulations. [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] More sophisticated methods to calculate the potential binding free energy of inhibitor candidate to the protein ranges from post molecular dynamics simulations such as Molecular 57 Recently several models using active learning such as ANI-1, 58 ANI-1x 59 and ANI-1cxx 60 Here, we introduce a new strategy to estimate free energies of solvation of small organic compounds and binding to proteins in explicit solvent using single end-state MD simulations. The method is adopted from ANI-1ccx neural network potentials (Machine Learning) for the The insertion of the ligand to an environment of solvent (solvation free energy) or receptor (binding free energy) can be defined by a coupling parameter, λ. cache = ./cache/cord-104122-klvx927g.txt txt = ./txt/cord-104122-klvx927g.txt === reduce.pl bib === id = cord-103915-rzy7mejb author = Duricki, Denise A. title = Corticospinal neuroplasticity and sensorimotor recovery in rats treated by infusion of neurotrophin-3 into disabled forelimb muscles started 24 h after stroke date = 2018-07-11 pages = extension = .txt mime = text/plain words = 12866 sentences = 671 flesch = 54 summary = We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. We also recently showed that injection of an adeno-associated viral vector (AAV) encoding full-length human NT3 (preproNT3, 30kDa) into forelimb muscles 24 hours after stroke in adult or elderly rats improved sensorimotor recovery 19 . We examined anatomical neuroplasticity in the C7 cervical spinal cord because we knew from experiments using adult and elderly rats that the less-affected corticospinal tract sprouts at this level (as well as other levels) after injection of AAV-NT3 into muscles including triceps brachii 19 . fMRI performed one week after stroke confirmed that somatosensory cortex was not active when the affected paw was stimulated in either vehicle or NT3 treated rats (p>0.05, Supplementary Fig. 6b ). Treatment of disabled arm muscles with NT3 protein, initiated 24 hours after stroke, caused changes in multiple locomotor circuits, and promoted a progressive recovery of sensory and motor function in rats. cache = ./cache/cord-103915-rzy7mejb.txt txt = ./txt/cord-103915-rzy7mejb.txt === reduce.pl bib === id = cord-103895-dt0ers70 author = Zeng, Xiangrui title = Comparative Pathway Integrator: a framework of meta-analytic integration of multiple transcriptomic studies for consensual and differential pathway analysis date = 2018-10-16 pages = extension = .txt mime = text/plain words = 4508 sentences = 269 flesch = 54 summary = Methods and Results We present a meta-analytic integration tool, Comparative Pathway Integrator (CPI), to address these issues using adaptively weighted Fisher's method to discover consensual and differential enrichment patterns, consensus clustering to reduce pathway redundancy, and a novel text mining algorithm to assist interpretation of the pathway clusters. In light of this, we proposed a framework of meta-analytical integration of multiple transcriptomic studies for consensual and differential pathway analysis, wrapped in a tool named Comparative Pathway Integrator (CPI). In order to identify both commonly and study-specifically enriched pathways, we applied the adaptively weighted Fisher's method [14] , which is originally developed to combine p-values from multiple genomic studies for detecting homogeneous and heterogeneous differentially expressed genes. In summary, CPI is a meta-analytic tool for discovering commonly expressed and study specific pattern in transcriptomic studies, that will also reduce pathway redundancy and conduct text mining to increase interpretability of the results. cache = ./cache/cord-103895-dt0ers70.txt txt = ./txt/cord-103895-dt0ers70.txt === reduce.pl bib === id = cord-104030-eb29t38n author = Morales-Nebreda, Luisa title = Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date = 2020-06-05 pages = extension = .txt mime = text/plain words = 3960 sentences = 175 flesch = 36 summary = Using heterochronic (age-mismatched) adoptive Treg cell transfer experiments and molecular profiling in mice, we sought to determine whether the age-related impairment in repair following influenza-induced lung injury is intrinsic to Treg cells. Our data support a paradigm in which aged Treg cells fail to upregulate youthful reparative programs, activate maladaptive responses and consequently exhibit a cell-autonomous impairment in pro-recovery function, which delays resolution from viralinduced lung injury in aged hosts. Gene set enrichment analysis of these genes demonstrated that this methylation-regulated gene expression program was associated with pro-recovery processes and was significantly skewed toward young Treg cells ( Figure 6C) . Combined, these results show that age-related DNA methylation regulates the pro-reparative transcriptional regulatory network during recovery from influenza-induced lung injury. What are the molecular mechanisms underpinning the age-associated Treg cell gain or loss-of pro-reparative function in the lung following influenza infection? cache = ./cache/cord-104030-eb29t38n.txt txt = ./txt/cord-104030-eb29t38n.txt === reduce.pl bib === id = cord-104138-qagyaegp author = Magee, Michelle title = Effects of face masks on acoustic analysis and speech perception: Implications for peri-pandemic protocols date = 2020-10-08 pages = extension = .txt mime = text/plain words = 2183 sentences = 138 flesch = 52 summary = Here we investigated how three face mask types (N95, surgical and cloth) affect acoustic analysis of speech and perceived intelligibility in healthy subjects. We compared speech produced with and without the different masks on acoustic measures of timing, frequency, perturbation and power spectral density. Our data show that face masks change the speech signal, but some specific acoustic features remain largely unaffected (e.g., measures of voice quality) irrespective of mask type. Where the interaction was significant, planned comparisons were made for each 1Khz frequency band to determine differences between masks types compared to no mask. For recordings produced with the tabletop microphone, there was a significant effect of mask type for percentage of pauses (F3,7.87=8.17, p=0.008), and spectral tilt (F3,8.39=15.43, p=0.001) ( Table 1) . We observed significant differences in acoustic power distribution across relevant frequency bands for speech in all three mask conditions compared to no mask. cache = ./cache/cord-104138-qagyaegp.txt txt = ./txt/cord-104138-qagyaegp.txt === reduce.pl bib === id = cord-104157-rivaoo73 author = Noreika, Valdas title = Alertness fluctuations during task performance modulate cortical evoked responses to transcranial magnetic stimulation date = 2019-06-28 pages = extension = .txt mime = text/plain words = 10469 sentences = 492 flesch = 52 summary = We observed rapid, non-linear changes in TMS-evoked neural responses – specifically, motor evoked potentials and TMS-evoked cortical potentials – as EEG activity indicated decreasing levels of alertness, even while participants remained awake and responsive in the behavioural task. Here we combined single-pulse TMS with concurrent EEG recording and a simple behavioural task to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. To assess the instantaneous level of alertness, a two-fold EEG analysis was applied over the time window immediately preceding each TMS pulse: (1) a binary definition of awake and drowsy states following EEG spectral power signatures (θ/α) averaged across all EEG electrodes (Bareham et al., 2014) , and (2) a dynamical definition of alertness levels following a detailed sub-staging system for scoring the transition to N1 sleep (Hori et al., 1994) (Fig. 1C ). cache = ./cache/cord-104157-rivaoo73.txt txt = ./txt/cord-104157-rivaoo73.txt === reduce.pl bib === id = cord-104142-0nfprn2a author = Azmi, Maryam A. title = A laboratory module that explores RNA interference and codon optimization through fluorescence microscopy using Caenorhabditis elegans date = 2020-10-19 pages = extension = .txt mime = text/plain words = 5438 sentences = 276 flesch = 50 summary = In this laboratory module, students learn about RNA interference (RNAi) and codon optimization using the research organism Caenorhabditis elegans (C. elegans Understand the process of RNA interference and importance of codon optimization Learn basic microscopy techniques and image analysis Learn how to properly use the scientific method Enhance critical thinking skills Learning Objectives Students will be able to: Lab 1 and 2: Identify specific larval stages of C. elegans larvae using alkaline hypochlorite treatment Understand codon usage Formulate hypotheses and design a controlled experiment Lab 3 and 4: Acquire images using an epifluorescence microscope Effectively communicate results and formulate conclusions from data Describe what RNAi is and how it affects gene expression/activity Calculate mean fluorescent intensity from acquired fluorescence micrographs Perform statistical tests to determine the significance of results Generate publication quality figures and figure legends cache = ./cache/cord-104142-0nfprn2a.txt txt = ./txt/cord-104142-0nfprn2a.txt === reduce.pl bib === id = cord-104031-vodwptdo author = Altshuler, Anna title = Capturing limbal epithelial stem cell population dynamics, signature, and their niche date = 2020-07-01 pages = extension = .txt mime = text/plain words = 10255 sentences = 580 flesch = 53 summary = Tremendous efforts have been made by many research groups to discover markers for the identification of LSCs. Keratin 15 (Krt15) 33 41 , C/EBPdelta and BMI1 42 , ABCB5 43 , ABCG2 44 and P63 45 represent a partial list of genes proposed to identify LSCs. Recently, we have shown that the Krt15-GFP transgene (green fluorescent protein coding gene under the promoter of Krt15) labeled a discrete population of murine LSCs. Krt15-GFP + basal limbal epithelial cells were located at close proximity to the site of corneal regeneration origin, as evident by lineage tracing of Krt14 + cells 33 . In silico analysis revealed discrete cell states in the corneal epithelial lineage Cell filtering and unbiased clustering were performed with R package Seurat 46 revealing 11 cell populations displaying a markedly distinct signature of gene expression (Fig. 1b, S1b) . cache = ./cache/cord-104031-vodwptdo.txt txt = ./txt/cord-104031-vodwptdo.txt === reduce.pl bib === id = cord-104001-5clslvqb author = Wang, Xiaoqi title = selfRL: Two-Level Self-Supervised Transformer Representation Learning for Link Prediction of Heterogeneous Biomedical Networks date = 2020-10-21 pages = extension = .txt mime = text/plain words = 5522 sentences = 292 flesch = 49 summary = The meta path detection-based self-supervised learning task is proposed to learn representation vectors that can capture the global-level structure and semantic feature in HBNs. The vertex entity mask-based self-supervised learning mechanism is designed to enhance local association of vertices. First, a meta path detection self-supervised learning mechanism is developed to train a deep Transformer encoder for learning low-dimensional representations that capture the path-level information on HBNs. Meanwhile, sel-fRL integrates the vertex entity mask task to learn local association of vertices in HBNs. Finally, the representations from the entity mask and meta path detection is concatenated for generating the embedding vectors of nodes in HBNs. The results of link prediction on six datasets show that the proposed selfRL is superior to 25 state-of-the-art methods. • We proposed a two-level self-supervised representation learning method for HBNs, where this study integrates the meta path detection and vertex entity mask selfsupervised learning task based on a great number of unlabeled data to learn high quality representation vector of vertices. cache = ./cache/cord-104001-5clslvqb.txt txt = ./txt/cord-104001-5clslvqb.txt === reduce.pl bib === id = cord-255069-9xueqdri author = Leary, Shay title = Three adjacent nucleotide changes spanning two residues in SARS-CoV-2 nucleoprotein: possible homologous recombination from the transcription-regulating sequence date = 2020-04-11 pages = extension = .txt mime = text/plain words = 1821 sentences = 77 flesch = 43 summary = The findings suggest that homologous recombination may have occurred since its introduction into humans and be a mechanism for increased viral fitness and adaptation of SARS-CoV-2 to human populations. Evidence of viral adaptation to selective pressures as it spreads among diverse human populations has implications for the ongoing potential for changes in viral fitness over time, which in turn may impact transmissibility, disease pathogenesis and immunogenicity. Here we describe a new emerging strain of SARS-CoV-2 within the LGG clade that appears to be the result of a homologous recombination event that introduced three adjacent nucleotide changes spanning two residues of the nucleocapsid protein. Evidence for such adaptations with closely linked compensatory mutations are known to occur under host immune pressure as is well established for other adaptable RNA viruses such as HIV 1,2 and Hepatitis C virus (HCV) 3 . cache = ./cache/cord-255069-9xueqdri.txt txt = ./txt/cord-255069-9xueqdri.txt === reduce.pl bib === id = cord-252910-7qvnj6c8 author = Li, Xin title = The discovery of a recombinant SARS2-like CoV strain provides insights into SARS and COVID-19 pandemics date = 2020-09-21 pages = extension = .txt mime = text/plain words = 4180 sentences = 223 flesch = 54 summary = In the present study, we identified key recombination regions and mutation sites cross the SARS-CoV-2, SARS-CoV and SARS-like CoV clusters of betacoronavirus subgroup B. Different from these studies, we previously reported several other findings on SARS-CoV-2 for the first time, including the following in particular: (1) the alternative translation of Nankai coding sequence (CDS) that characterize the rapid mutation rate of betacoronavirus at the nucleotide level [2] ; (2) a furin cleavage site (FCS) "RRAR" in the junction region between S1 and S2 subunits (junction FCS) of SARS-CoV-2 that may increase the efficiency of viral entry into cells [3] ; and (3) the use of 5' untranslated-region (UTR) barcoding for the detection, identification, classification and phylogenetic analysis of-though not limited to-CoVs [4] . Using the insertions and deletions (InDels) at six sites, we identified two recently detected betacoronavirus strains RmYN01 and RmYN02 from a bat [6] and discovered that RmYN02 was a recombinant SARS2-like CoV strain. cache = ./cache/cord-252910-7qvnj6c8.txt txt = ./txt/cord-252910-7qvnj6c8.txt === reduce.pl bib === id = cord-253987-83h861lp author = Tada, Takuya title = A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture date = 2020-09-17 pages = extension = .txt mime = text/plain words = 6830 sentences = 349 flesch = 50 summary = The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. In SARS-CoV-2 entry, the virus attaches to the target cell through the interaction of the spike glycoprotein (S) with its receptor, the angiotensin-converting enzyme 2 (ACE2) (Li, 2015; Li et al., 2005; Li et al., 2003) , a plasma membrane protein carboxypeptidase that degrades angiotensin II to angiotensin-(1-7) [Ang-(1-7)] a vasodilator that promotes sodium transport in the regulation of cardiac function and blood pressure (Kuba et al., 2010; Riordan, 2003; Tikellis and Thomas, 2012) . To determine the relative antiviral activity of soluble ACE2 and the ACE2 microbody proteins, we tested their ability to block the infection SARS-CoV-2 Δ19 S protein pseudotyped GFP/luciferase reporter virus. cache = ./cache/cord-253987-83h861lp.txt txt = ./txt/cord-253987-83h861lp.txt === reduce.pl bib === id = cord-104055-47ren7ie author = Lutkenhoff, Evan S. title = EEG power spectra and subcortical pathology in chronic disorders of consciousness date = 2020-09-01 pages = extension = .txt mime = text/plain words = 2479 sentences = 127 flesch = 49 summary = Objective To determine (i) the association between long-term impairment of consciousness after severe brain injury, spontaneous brain oscillations, and underlying subcortical damage, and (ii) whether such data can be used to aid patient diagnosis, a process known to be susceptible to high error rates. Conclusions These results ground, for the first time, electroencephalographic presentation detected with routine clinical techniques in the underlying brain pathology of disorders of consciousness and demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of this patient cohort. Sex, 19 age, time-post-injury, etiology (i.e., TBI vs non-TBI), were included as covariates, 20 along with NBV (to ensure that observed tissue displacement reflect local subcortical 21 shape changes independent of overall brain atrophy ( In this analysis, we related the patients' behavioral presentation, as captured by the 7 CRS-R subscales, with subcortical atrophy. cache = ./cache/cord-104055-47ren7ie.txt txt = ./txt/cord-104055-47ren7ie.txt === reduce.pl bib === id = cord-104092-yau3r79c author = Tamming, Renee J. title = Atrx deletion in neurons leads to sexually-dimorphic dysregulation of miR-137 and spatial learning and memory deficits date = 2019-04-13 pages = extension = .txt mime = text/plain words = 4063 sentences = 206 flesch = 47 summary = Mechanistically, we identify ATRX-dependent and sex-specific alterations in synaptic gene expression linked to Mir137 levels, a known regulator of presynaptic processes and spatial memory. Summary statement Ablation of the ATRX chromatin remodeler specifically in forebrain excitatory neurons of mice causes male-specific deficits in long-term spatial memory associated with miR-137 overexpression, transcriptional changes and structural alterations corresponding to preand post-synaptic abnormalities. A comprehensive analysis of these mice reveals that ATRX promotes long-term spatial learning and memory associated with morphological and synaptic ultrastructural changes in the hippocampus. We show that female mice lacking ATRX in neurons are protected from spatial learning and memory defects and identify sex-specific effects of ATRX loss on the expression of synaptic genes and miR-137. This study presents evidence that ATRX is required in a sex-specific manner in excitatory forebrain neurons for normal spatial learning and memory (Figure 8) [75] [76] [77] . cache = ./cache/cord-104092-yau3r79c.txt txt = ./txt/cord-104092-yau3r79c.txt === reduce.pl bib === id = cord-104146-pabh3ajb author = de Lussanet de la Sablonière, Marc H. E. title = Robust, general purpose, digital power line hum filter which is free of deformations and which can be applied to large transients date = 2019-11-04 pages = extension = .txt mime = text/plain words = 3463 sentences = 199 flesch = 66 summary = The resulting periodic median subtraction (PMS) filter reliably removes hum of any harmonic composition, even if the ground frequency is lacking. Even though power 25 line noise is mostly highly regular in frequency, amplitude and wave form, it has proven notoriously difficult to design a filter that is free of artifacts and deformations, which leaves the original signal intact. Subtraction-type filters aim to fit the shape and amplitude of the hum 50 noise directly from the data, sometimes from multiple channels (e.g., in EEG signals) or from a reference channel (e.g. Wan et al., 2006; Lin et al., 2016) . Increasing the filter window of the PMS filter from 50 to 500 periods (10 s) reduced the median absolute error in white noise data to 0.037, which is equivalent to the error in a signal with an HF amplitude of 0.2 (cf. cache = ./cache/cord-104146-pabh3ajb.txt txt = ./txt/cord-104146-pabh3ajb.txt === reduce.pl bib === id = cord-104162-fe51v2pt author = Zhang, Chiyu title = Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy date = 2020-11-02 pages = extension = .txt mime = text/plain words = 3745 sentences = 208 flesch = 49 summary = Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions – such as the ribosomal frameshifting element (FSE) that facilitates differential expression of 1a and 1ab polyproteins – can be considered potential "Achilles heels" for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. Assays of the base order-dependent component of the folding energy have shown that a highly conserved region, in otherwise rapidly mutating HIV-1 genomes, associates with an RNA structure corresponding, not to a protein-encoding function, but to an RNA packaging signal. This high GC% value can obscure the contribution of the base order-dependent component of the folding energy, which provides a sensitive indicator of local intraspecies pressures for the conservation of function within a population (i.e. a mutated organism is eliminated by natural selection so no longer can be assayed for function in the population). cache = ./cache/cord-104162-fe51v2pt.txt txt = ./txt/cord-104162-fe51v2pt.txt === reduce.pl bib === id = cord-103868-iwpiti2h author = Harrison, Angela R. title = The Ebola virus interferon antagonist VP24 undergoes active nucleocytoplasmic trafficking date = 2020-08-11 pages = extension = .txt mime = text/plain words = 2255 sentences = 124 flesch = 45 summary = Functions of the Ebola virus (EBOV) IFN antagonist VP24 include nucleocapsid assembly during cytoplasmic replication and inhibition of IFN-activated signalling by STAT1. Proteins of many viruses with cytoplasmic replication cycles similar to EBOV interact with the nuclear trafficking machinery, resulting in active nucleocytoplasmic shuttling important to immune evasion and other intranuclear functions. Thus, it appears that active In this study we have shown that EBOV VP24 undergoes active trafficking between the nucleus 275 and cytoplasm involving CRM1-dependent nuclear export via a NES at the VP24 C-terminus. Notably, the EBOV 287 matrix protein VP40 has also been reported to localise to the nucleus in infected and transfected 288 cells (16, 50); however, a direct role for active trafficking pathways to regulate localisation, 289 distinct from mechanisms such as diffusion or interaction with other host factors, has not been 290 defined. cache = ./cache/cord-103868-iwpiti2h.txt txt = ./txt/cord-103868-iwpiti2h.txt === reduce.pl bib === id = cord-104140-o46kvd0b author = McPherson, Malinda J. title = Harmonicity aids hearing in noise date = 2020-09-30 pages = extension = .txt mime = text/plain words = 9606 sentences = 533 flesch = 51 summary = To explore whether harmonic frequency relations aid hearing of sounds in noise, we compared detection and discrimination of harmonic and inharmonic tones and spoken vowels embedded in noise. However, detection thresholds were substantially better for harmonic than inharmonic complex tones even though they each had 10 frequency components (significant differences in both sine and random phase conditions, Wilcoxon signed-rank test: sine phase: Z=6.97, p<.001; random phase: Z=6.83, p<.001). Specifically, it seemed plausible that being better able to separate tones from noise might help listeners discriminate successive tones at low SNRs. Using an adaptive procedure, we measured traditional up-down discrimination thresholds for Harmonic, Inharmonic, and Pure Tone conditions (Fig. 3a) at a range of SNRs. Participants. We replotted the pitch discrimination curves in terms of the SNR relative to the detection thresholds measured in Experiment 1 (-21.00 dB SNR, -19.77 dB SNR, -17.39 dB SNR, for Harmonic, Inharmonic and Pure Tone conditions, respectively, Fig. 2b, inset) . cache = ./cache/cord-104140-o46kvd0b.txt txt = ./txt/cord-104140-o46kvd0b.txt === reduce.pl bib === id = cord-104161-jvbgouv8 author = Pfrieger, Frank W. title = Insight into the workforce advancing fields of science and technology date = 2020-06-02 pages = extension = .txt mime = text/plain words = 3052 sentences = 197 flesch = 47 summary = Context-specific, but citation-independent metrics gauge team impact and reveal key contributors valuing publication output, mentorship and collaboration. Based on scientific articles related to a specific topic, this approach reveals instantly the teams working in a research field, visualizes workforce growth, delineates family and collaborative connections and gauges team performance in a citation-independent manner. A PubMed query using the term "circadian clock" (Clock) yielded a list of articles published between 1960 and 2020, from which TTA identified principal investigators (PIs)/teams working in the field based on last author names (Table 1 ; Supplementary Data 1). The Clock field expanded steadily in terms of workforce and of publication output as indicated by annual counts of newly entering teams and of published articles, respectively (Fig. 1A) . Individual PIs/teams published up to 113 articles (PC, publication count) as last authors (Last) with a maximum annual output of nearly 7 papers per year. cache = ./cache/cord-104161-jvbgouv8.txt txt = ./txt/cord-104161-jvbgouv8.txt === reduce.pl bib === id = cord-104037-39kk37fb author = Ma, Jiahao title = Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19 date = 2020-09-21 pages = extension = .txt mime = text/plain words = 2720 sentences = 153 flesch = 62 summary = Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The newly-formed structural motif makes 152 direct contact with the previously identified pH switch 1 of the adjacent protomer, 153 accounting for the enhanced stability of the WT S-Trimer at lower pH (Fig. 3A) . When revisiting the electron density map for full-163 length wild-type S protein (EMDB: 22292), we spotted unassigned density at the become predominant over the ancestral form worldwide and has been shown to interaction with K854 at the conformational switch region (Fig. 4C ). Purified MT S-trimer protein diluted to 0.2 and 0.5 mg/ml in PBS buffer were applied to glow-discharged gold holey carbon 1.2/1.3 300-mesh grids with and without graphene oxide, respectively. cache = ./cache/cord-104037-39kk37fb.txt txt = ./txt/cord-104037-39kk37fb.txt === reduce.pl bib === id = cord-104109-k36jya0b author = Das Jana, Indrani title = Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus date = 2020-09-02 pages = extension = .txt mime = text/plain words = 1765 sentences = 116 flesch = 49 summary = title: Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus In this work, we have screened a series of nanoparticles and their composites for antiviral activity using Nano Luciferase based highly sensitive influenza A reporter virus. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide embedded graphene sheet architecture that can inactivate the virion particles only within 30 minutes of pre-incubation and subsequently interferes with the entry of these virion particles into the host cell. This data 142 suggests that the Nano-luciferase influenza A reporter virus could serve as an excellent tool to study the 143 antiviral activity of various nanoparticles or their nanocomposites used in this study. Briefly, Nano-luciferase influenza A reporter viruses were pre-incubated with the 5uM colloidal 146 suspensions of each of the nanoparticles/ composites or with the vehicle control for 30 minutes at room 147 temperature and subsequently used to infect MDCK cells at an MOI of 0.1. cache = ./cache/cord-104109-k36jya0b.txt txt = ./txt/cord-104109-k36jya0b.txt === reduce.pl bib === id = cord-104133-d01joq23 author = Arthur, Ronan F. title = Adaptive social contact rates induce complex dynamics during epidemics date = 2020-07-14 pages = extension = .txt mime = text/plain words = 5240 sentences = 300 flesch = 55 summary = We develop a model for adaptive optimal control of the effective social contact rate within a Susceptible-Infectious-Susceptible (SIS) epidemic model using a dynamic utility function with delayed information. To represent endogenous behavior-change, we start with the classical discrete-time 112 susceptible-infected-susceptible (SIS) model [28] , which, when incidence is relatively 113 small compared to the total population [29, 30] , can be written in terms of the recursions 114 In order to introduce human behavior, we 121 substitute for b a time-dependent b t , which is a function of both b 0 , the probability that 122 disease transmission takes place on contact, and a dynamic social rate of contact c t 123 whose optimal value, c * t , is determined at each time t as in economic epidemiological 124 models [31] , namely cache = ./cache/cord-104133-d01joq23.txt txt = ./txt/cord-104133-d01joq23.txt === reduce.pl bib === id = cord-104025-ysxc7rpl author = Cheek, Martin title = Deinbollia onanae (Sapindaceae), a new, Endangered, montane tree species from the Cameroon Highlands date = 2020-10-26 pages = extension = .txt mime = text/plain words = 3999 sentences = 235 flesch = 61 summary = title: Deinbollia onanae (Sapindaceae), a new, Endangered, montane tree species from the Cameroon Highlands Deinbollia onanae is an infrequent tree species known from five locations in surviving islands of montane (or upper submontane) forest along the line of the Cameroon Highlands. As part of the project to designate Important Plant Areas (IPAs) in Cameroon (also known as Tropical Important Plant Areas or TIPAs), we are striving to name, assess the conservation status and include in IPAs (Darbyshire et al., 2017) rare and threatened plant species in the surviving, threatened natural habitat of the Cross-Sanaga interval (Cheek et al., 2001) . Apart from Deinbollia onanae, the only other montane tree species endemic to the Cameroon Highland chain are the nearly extinct Ternstroemia cameroonensis Cheek (Cheek et al., 2017) and the more common and widespread Schleffera mannii (Hook.f.)Harms (Keay, 1958) . cache = ./cache/cord-104025-ysxc7rpl.txt txt = ./txt/cord-104025-ysxc7rpl.txt === reduce.pl bib === id = cord-103990-qvuv289g author = Amster, Guy title = Changes in life history and population size can explain relative neutral diversity levels on X and autosomes in extant human populations date = 2019-09-09 pages = extension = .txt mime = text/plain words = 5518 sentences = 280 flesch = 47 summary = We revisit this question in light of our new theory about the effects of life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly higher generation times in males than females, likely had multiple effects on human X-to-autosomes (X:A) polymorphism ratios, through the extent of male mutation bias, the equilibrium X:A ratios of effective population sizes, and differential responses to changes in population size. Our results suggest that ancestral human populations were highly polygynous; that non-African populations experienced a substantial reduction in polygyny and/or increase in male-biased generation times around the out of Africa bottleneck; and that extant diversity levels were affected by fairly recent changes in sex-specific life history. Indeed, we show that the ratios observed across human populations can be explained by demographic history, assuming plausible, sex-specific mutation rates, generation times and reproductive variances. cache = ./cache/cord-103990-qvuv289g.txt txt = ./txt/cord-103990-qvuv289g.txt === reduce.pl bib === id = cord-104073-vsa5y7ip author = Warner, Emily F. title = Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date = 2020-09-23 pages = extension = .txt mime = text/plain words = 3218 sentences = 207 flesch = 54 summary = PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. PQS in the 35 clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida 36 albicans were located within genes (particularly coding regions), mRNA, repeat regions, 37 cache = ./cache/cord-104073-vsa5y7ip.txt txt = ./txt/cord-104073-vsa5y7ip.txt === reduce.pl bib === id = cord-253447-4w6caxwu author = Zeng, Xin title = Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy date = 2020-04-20 pages = extension = .txt mime = text/plain words = 2866 sentences = 161 flesch = 54 summary = title: Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy SARS-CoV-2 relies on its spike protein, in particular the receptor binding domain (RBD), to bind human cell receptor angiotensin-converting enzyme 2 (ACE2) for viral entry, and thus targeting RBD holds the promise for preventing SARS-CoV-2 infection. In this work, a competitive biopanning strategy of a phage display antibody library was applied to screen blocking antibodies against RBD. It was proved to competitively block the binding of RBD to ACE2 protein, and potently inhibit SARS-CoV-2 pseudovirus infection of ACE2-overexpressing Hela cells with IC50 values of 12nM. Several high-affinity antibodies targeting SARS-CoV-2 RBD and blocking its binding to ACE2 were isolated, and the top 1 lead exhibited a neutralization activity of SARS-CoV-2 pseudotyped VSV infection. A high-affinity antibody against the target protein can be screened from a phage display antibody library using the standard biopanning process, but its binding epitopes are identified by some extra steps, such as epitope mapping and competitive ELISA. cache = ./cache/cord-253447-4w6caxwu.txt txt = ./txt/cord-253447-4w6caxwu.txt === reduce.pl bib === id = cord-254855-gmy9zyad author = He, Sijia title = PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity date = 2020-07-06 pages = extension = .txt mime = text/plain words = 1700 sentences = 94 flesch = 51 summary = Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks virus attachment and infection of target cells. Together, these results demonstrate that PSGL-1 expression in the virus-producer cells severely diminishes the infectivity of virions bearing SARS coronavirus S proteins. We and other previously reported that PSGL-1-mediated inhibition of virion infectivity is through steric hindrance of particle attachment to target cells, which does not depend on the presence of viral envelope glycoproteins (1, 5) . We performed a virion attachment assay and observed that the lentiviral particles pseudotyped with SARS-CoV or SARS-CoV-2 S protein produced from PSGL-1-expressing cells were impaired in their ability to attach to target cells (Fig. 2D) . These results demonstrate that the presence of PSGL-1 on virus particles can structurally hinder virion interaction with the target cells even in the presence of remaining S proteins, consistent with previous studies of PSGL-1 and HIV-1 infection (1, 5) . cache = ./cache/cord-254855-gmy9zyad.txt txt = ./txt/cord-254855-gmy9zyad.txt === reduce.pl bib === id = cord-104128-0gyk9cwx author = Morand, Serge title = The accelerated infectious disease risk in the Anthropocene: more outbreaks and wider global spread date = 2020-04-20 pages = extension = .txt mime = text/plain words = 7037 sentences = 358 flesch = 47 summary = Countries which are more centrally located within these disease networks tend to be also the more developed and emerging countries with significantly higher GDPs. Therefore, one cost of increased global mobility (which is currently tightly linked to economic growth and globalization, see Discussion below) is the increased risk of disease outbreaks and their faster and wider spread (although we note that the risk per capita may be decreasing, Smith et al., 2014) . Similarly, increasing levels of (1) isolation of infectious hosts, household quarantine and related behavioral changes which reduce transmission rates and (2) air traffic reduction increasingly slowed the global spread of influenza, although the latter control strategy required the almost complete halt of global air traffic (Cooper et al., 2006; Ferguson et al., 2006; Flahault et al., 2006; Hollingsworth et al., 2006; Epstein et al., 2007; Bajardi 11 et al., 2011) . cache = ./cache/cord-104128-0gyk9cwx.txt txt = ./txt/cord-104128-0gyk9cwx.txt === reduce.pl bib === id = cord-252097-4kslllaq author = Kaur, S. title = Local computational methods to improve the interpretability and analysis of cryo-EM maps date = 2020-06-19 pages = extension = .txt mime = text/plain words = 5987 sentences = 312 flesch = 54 summary = In this work, we propose 1) approaches to enhance high-resolution features of cryo-EM maps, while preventing map distortions and 2) methods to obtain local B-factors and electron density occupancy maps. Secondly, we also propose approaches to determine local B-factors and density occupancy maps to improve the analysis of cryo-EM reconstructions. The link between the different proposed approaches is the use of the spiral phase transform to estimate a modulation or amplitude map of the cryo-EM reconstruction at different resolutions. In the second row of Figure 2 , we show maps with improved contrast at high-resolution obtained after processing EMD-8441 by the LocSpiral method and by Relion (Fernandez, Luque et al. The common link between all these approaches is the use of the spiral phase transform, which is used to factorize cryo-EM maps into amplitude and phase terms in real space for different resolutions. cache = ./cache/cord-252097-4kslllaq.txt txt = ./txt/cord-252097-4kslllaq.txt === reduce.pl bib === id = cord-258630-mvz2l3yj author = Liu, Tiantian title = A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples date = 2020-11-10 pages = extension = .txt mime = text/plain words = 11041 sentences = 596 flesch = 57 summary = We compared seven different library construction protocols and specifically evaluated the cross-protocol performance in sequencing read mappability, viral genome coverage percentage and uniformity, effect of sequence depth, SNV calling concordance (reproducibility), precision (positive predictive value), and sensitivity (proportion of consensus variants identified at different sequencing depths and viral copy number inputs) across protocols. Here, we compared seven WGS protocols for SARS-CoV-2 using clinical samples from infected patients, benchmarking the performances of these protocols in several aspects including the sequencing read mappability, genome coverage (percentage and uniformity, minimum sequences required); sample storage condition; effects of viral input, sequencing depth, length and platform; sensitivity, reproducibility and precision of SNV calling and related assay factors (e.g., amount of viral input, sequencing depth and bioinformatics pipeline). cache = ./cache/cord-258630-mvz2l3yj.txt txt = ./txt/cord-258630-mvz2l3yj.txt === reduce.pl bib === id = cord-104081-a3fx8tyd author = Tang, Tiffany title = Proteolytic activation of the SARS-CoV-2 spike S1/S2 site: a re-evaluation of furin cleavage date = 2020-10-05 pages = extension = .txt mime = text/plain words = 4004 sentences = 206 flesch = 57 summary = The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its spike (S) protein to mediate viral entry into host cells. Our results demonstrate that S1/S2 pre-cleavage is essential for plasma membrane entry into Calu-3 cells, a model lung epithelial cell line, but not for endosomal entry Vero E6 cells, a model cell culture line, and that other proteases in addition to furin are responsible for processing SARS-CoV-2 S1/S2. dec-RVKR-CMK treatment had no significant impact on SARS-CoV S mediated infection of Vero E6 and Calu-3 cells (Figure 6A and 6B) , suggesting that dec-RVKR-CMK impacts on SARS-CoV-2 S is due to inhibiting the S1/S2 pre-cleavage and not due to some general effect on protein expression. Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2 Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells cache = ./cache/cord-104081-a3fx8tyd.txt txt = ./txt/cord-104081-a3fx8tyd.txt === reduce.pl bib === id = cord-255440-ls1l2mlg author = Tindle, Courtney title = Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19 date = 2020-10-18 pages = extension = .txt mime = text/plain words = 9951 sentences = 525 flesch = 53 summary = Besides the approaches described so far, there are a few more approaches used for modeling COVID-19-(i) 3D organoids from bronchospheres and tracheospheres have been established before (Hild and Jaffe, 2016; Rock et al., 2009; Tadokoro et al., 2016) and are now used in apical-out cultures for infection with SARS-COV-2 (Suzuki et al., 2020); (ii) the most common model used for drug screening is the air-liquid interphase (ALI model) in which pseudo-stratified primary bronchial or small airway epithelial cells are used to recreate the multilayered mucociliary epithelium (Mou et al., 2016; Randell et al., 2011) ; (iii) several groups have also generated 3D airway models from iPSCs or tissue-resident stem cells (Dye et al., 2015; Ghaedi et al., 2013; Konishi et al., 2016; McCauley et al., 2017; Miller et al., 2019; Wong et al., 2012) ; (iv) others have generated AT2 cells from iPSCs using closely overlapping protocols of sequential differentiation starting with definitive endoderm, anterior foregut endoderm, and distal alveolar expression (Chen et al., 2017; Gotoh et al., 2014; Huang et al., 2014; Jacob et al., 2017; Jacob et al., 2019; Yamamoto et al., 2017) . cache = ./cache/cord-255440-ls1l2mlg.txt txt = ./txt/cord-255440-ls1l2mlg.txt === reduce.pl bib === id = cord-258914-g6pv8zz9 author = Proud, Pamela C. title = Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date = 2020-09-25 pages = extension = .txt mime = text/plain words = 1191 sentences = 90 flesch = 51 summary = title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. The TLRs are key microbe-recognition receptors with a crucial role in 97 activation of host defence and protection from infections and therefore attractive drug 98 targets against infectious diseases [12] [13] [14] To determine whether TLR2/6 agonists are also active against SARS-CoV-2, we used In life samples were taken at days 1, 3, 5, 7, 10 and 12, with scheduled culls at days 137 3 (n=6) and end of study days 12-14 (n=18) (Fig 1A) . cache = ./cache/cord-258914-g6pv8zz9.txt txt = ./txt/cord-258914-g6pv8zz9.txt === reduce.pl bib === id = cord-252597-ea78sjcs author = Ramazzotti, Daniele title = VERSO: a comprehensive framework for the inference of robust phylogenies and the quantification of intra-host genomic diversity of viral samples date = 2020-10-19 pages = extension = .txt mime = text/plain words = 10701 sentences = 502 flesch = 45 summary = Moreover, the in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and allows us to identify a number of variants that are transiting from minor to clonal state in the population, as well as several homoplasies, some of which might indicate ongoing positive selection processes. The outbreak of coronavirus disease 2019 (COVID19) , which started in late 2019 in Wuhan (China) [1, 2] and was declared pandemic by the World Health Organization, is fueling the publication of an increasing number of studies aimed at exploiting the information provided by the viral genome of SARS-CoV-2 virus to identify its proximal origin, characterize the mode and timing of its evolution, as well as to define descriptive and predictive models of geographical spread and evaluate the related clinical impact [3, 4, 5] . cache = ./cache/cord-252597-ea78sjcs.txt txt = ./txt/cord-252597-ea78sjcs.txt === reduce.pl bib === id = cord-104036-790vk1cf author = Liekkinen, Juho title = Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level date = 2020-07-08 pages = extension = .txt mime = text/plain words = 6533 sentences = 376 flesch = 44 summary = In this work, we combined all-atom molecular dynamics simulations, Langmuir trough measurements, and AFM imaging to study synthetic four-component lipid monolayers designed to model protein-free pulmonary surfactant. 22 It has been shown that the pulmonary surfactant monolayers and membranes exhibit phase behaviour that is believed to play roles in lung mechanics; tight packing of lipids with saturated lipid chains promotes its ability to lower surface tension, whereas lipids with unsaturated chains increase pulmonary surfactant fluidity and thus allow for its rapid adsorption to the air-water interface. By using our recently developed protocol for performing simulations of lipid monolayers at the air-water interface, 33, 46 we were able to reach quantitative agreement with experimental surface pressure-area isotherms. Plateau Surface pressure-area isotherm is a key quantity representing monolayer behavior at the water-air interface, and it is readily extracted from both Langmuir trough measurements and computer simulations. cache = ./cache/cord-104036-790vk1cf.txt txt = ./txt/cord-104036-790vk1cf.txt === reduce.pl bib === id = cord-256607-wpywh8c9 author = Itokawa, Kentaro title = Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR date = 2020-06-01 pages = extension = .txt mime = text/plain words = 1415 sentences = 76 flesch = 59 summary = The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network's original (V1) and modified (V3) primer set. Alongside with this modification, the ARTIC Network itself released another 108 modified version of primer set known as V3 in 24 th March 2020 (Loman and Quick 2020) after replacement for the same clinical sample (previously deposited to GISAID with ID EPI_ISL_416596, Ct=28.5, 1/25 input per reaction). Fig 3 Abundance of 98 amplicons at 8 different annealing/extension temperatures with the three different primer sets on a same clinical sample (previously deposited to GISAID with ID EPI_ISL_416584, Ct=16, 1/300 input per reaction). The orange lines and points indicate the abundances of amplicons whose primers were not modified but predicted to be eliminated the adverse primer interactions in the N1 primer set. cache = ./cache/cord-256607-wpywh8c9.txt txt = ./txt/cord-256607-wpywh8c9.txt === reduce.pl bib === id = cord-255552-k1retwa4 author = Gassen, Nils C. title = Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date = 2020-04-15 pages = extension = .txt mime = text/plain words = 1208 sentences = 73 flesch = 39 summary = Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In the case of highly pathogenic Middle East respiratory syndrome 57 (MERS)-CoV, we recently showed that autophagy is limited by a virus-induced AKT1-dependent 58 activation of the E3-ligase S-phase kinase-associated protein 2 (SKP2), which targets the key autophagy 59 initiating protein Beclin-1 (BECN1) for proteasomal degradation (10). Direct blocking of the negative BECN1 regulator SPK2 by previously 175 described inhibitors SMIP004, SMIP004-7, valinomycin, and niclosamide (10) showed SARS-CoV-2 176 growth inhibition from 50 (SMIP004, SMIP004-7) to over 99% in case of valinomycin and niclosamide 177 (Figure 4a, lower panel, Figure S3d,e) . cache = ./cache/cord-255552-k1retwa4.txt txt = ./txt/cord-255552-k1retwa4.txt === reduce.pl bib === id = cord-255755-5jccb3nh author = Saha, Sovan title = Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network date = 2020-04-23 pages = extension = .txt mime = text/plain words = 3668 sentences = 212 flesch = 59 summary = title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network The new network attribute spreadability index along with generated SIS values of selected top spreader nodes when compared with the other network centrality based methodologies like Degree centrality (DC), Closeness centrality (CC), Local average centrality (LAC) and Betweeness centrality (BC) is found to perform relatively better than the existing-state-of-art. In the proposed methodology, Protein-protein interaction network (PPIN) has been used as the central component in identification of spreader nodes in SARS-CoV. Once it is formed, spreader nodes are identified in each of SARS-CoV proteins, its level 1 and level 2 of human network by the application of a new network attribute i.e. spreadability index which is a combination of three terminologies: 1) edge ratio [28] 2) neighborhood density [28] and 3) node weight [29] . cache = ./cache/cord-255755-5jccb3nh.txt txt = ./txt/cord-255755-5jccb3nh.txt === reduce.pl bib === id = cord-104169-2sbc1guz author = Satish, Swarup title = The impact of preprint servers in the formation of novel ideas date = 2020-10-08 pages = extension = .txt mime = text/plain words = 4803 sentences = 306 flesch = 59 summary = Our proposed Bayesian Approach to Novelty Detection (BAND) finds the time interval τ that maximizes the observed series of publication frequency for a phrase (Figure 1 ). Our motivation for finding τ using BAND is to compare the impact of different publication venues (i.e. preprint servers and peer-reviewed journals) that cover overlapping research topics. In our analysis (Section 5.2), we compare these methods to BAND not only for finding the first clear inflection point, but also how relevant τ is for the end goal of novelty detection and comparing research impact. • Can we find the point τ in time when a phrase is determined novel using our Bayesian Approach to Novelty Detection (BAND)? Our findings indicate that novel phrases, which we use as a proxy for new ideas, in most cases appear on pre-print servers and in peer reviewed journals. cache = ./cache/cord-104169-2sbc1guz.txt txt = ./txt/cord-104169-2sbc1guz.txt === reduce.pl bib === id = cord-254772-1xzkfl8g author = Pandolfi, Laura title = Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis date = 2020-11-09 pages = extension = .txt mime = text/plain words = 4248 sentences = 252 flesch = 55 summary = Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1β, best-known inducers of NETosis. Because of the high levels of NETs in the BAL of COVID-19 patients and their potential role in inducing the EMT, we next focused on the correlation between NETs and the EMT by setting up an in vitro alveolar model that we infected with SARS-CoV-2. In particular, we would like to propose a model in which macrophages, by releasing IL8 and IL1β, two cytokines significantly increased in the plasma (32, 33) and BAL-fluid of severe COVID-19 patients (14), potentiate the capacity of NETs released by Neu to amplify the noxious activity on lung cells, favoring the EMT. cache = ./cache/cord-254772-1xzkfl8g.txt txt = ./txt/cord-254772-1xzkfl8g.txt === reduce.pl bib === id = cord-255325-tl5fm2yu author = Goletic, Teufik title = Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches date = 2020-06-19 pages = extension = .txt mime = text/plain words = 1726 sentences = 95 flesch = 49 summary = Objectives of this research were: To share obtained sequences of the complete genome of SARS-CoV-2 strains from clinical samples of BiH patients diagnosed with COVID-19, and To contribute to the understanding of the interaction of molecular and classical epidemiology findings of COVID 19 in BH and the whole region and give recommendations for the improvement of prevention and future measures. Livno and Banja Luka samples WGS was performed according to the ARTIC amplicon sequencing protocol for MinION for nCoV-2019, which uses two primer pools to generate the sequence, as described elsewhere [7] . The constructed phylogenetic tree in Figure 2 indicates probable multiple independent introduction events as reflected by clustering of each single BiH sequence in a separate cluster, highlighted with red (Livno, EPI_ISL_462753), green (Banja Luka, EPI_ISL_462990), blue (Sarajevo, EPI_ISL_467300) and purple (Tuzla, EPI_ISL_463893). cache = ./cache/cord-255325-tl5fm2yu.txt txt = ./txt/cord-255325-tl5fm2yu.txt === reduce.pl bib === id = cord-260508-z11exbyu author = Wang, Hongru title = Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date = 2020-10-12 pages = extension = .txt mime = text/plain words = 4698 sentences = 272 flesch = 58 summary = Phylogenetic analyses (Fig. 2 ) in genomic regions with all recombination tracts 6 (Supplementary Table 5 ) masked using Maximum-likelihood (Fig. 2a) and Neighbor-joining 7 based on synonymous (Fig. 2b ) or non-synoymous (Fig. 2c ) mutation distance metrics, 8 consistently support RmYN02 as the nearest outgroup to human SARS-CoV-2, in contrast to 9 previous analyses before the discovery of RmYN02, which instead found RaTG13 to be the 10 nearest outgroup ). Notice that the divergences 14 between human SARS-CoV-2 and the bat viral sequences, RaTG13 and RmYN02, in most 15 regions of the genome, are quite low compared to the other comparisons. While the overall divergence in the S gene encoding the spike protein could suggest the 10 presence of recombination in the region, previous study ) reported that the tree 11 based on synonymous substitutions supported RaTG13 as the sister taxon to the human SARS-12 cache = ./cache/cord-260508-z11exbyu.txt txt = ./txt/cord-260508-z11exbyu.txt === reduce.pl bib === id = cord-254636-3lr008th author = Shishir, Tushar Ahmed title = In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date = 2020-08-16 pages = extension = .txt mime = text/plain words = 2974 sentences = 171 flesch = 54 summary = We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. We conducted comparative analysis of publicly available genome sequences of SARS-CoV-2 from 27 countries to predict the origin of viruses in Bangladesh by studying a time-4 resolved phylogenetic relationship. Later, we analyzed the variants present in different isolates of Bangladesh to understand the pattern of mutations in relation to the ancestral Wuhan strain, find unique mutations, and possible effect of these mutations on the stability of encoded proteins, and selection pressure on genes. cache = ./cache/cord-254636-3lr008th.txt txt = ./txt/cord-254636-3lr008th.txt === reduce.pl bib === id = cord-259246-azt5sr9w author = Peng, Qi title = Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir date = 2020-10-19 pages = extension = .txt mime = text/plain words = 3216 sentences = 158 flesch = 50 summary = This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. Recently, we and other groups have determined the structures of SARS-CoV-2 core polymerase complex in both apo and RNA-bound states 26-30 , providing important information for structure-based antiviral drug design. Similar observations were also reported recently that SARS-CoV-2 polymerase is more tolerant for mismatches between template and product residues than other viral RdRps 5 , which further highlights the requirement for the proofreading nuclease nsp14 to maintain the integrity of viral genome. Interestingly, Favipiravir could be incorporated into the RNA product with similar efficiencies to those of ATP or GTP substrates guided by U or C template residues, respectively (Fig. 1c) . cache = ./cache/cord-259246-azt5sr9w.txt txt = ./txt/cord-259246-azt5sr9w.txt === reduce.pl bib === id = cord-255371-o9oxchq6 author = Nguyen, Thanh Thi title = Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) date = 2020-07-10 pages = extension = .txt mime = text/plain words = 5640 sentences = 365 flesch = 59 summary = title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. We use 6,324 SARS-CoV-2 genome sequences collected in 45 countries and deposited to the NCBI GenBank so far and create a spreadsheet dataset of all mutations occurred across different genes. In this paper, to evaluate the possible impacts of genomic mutations on the virus functions, we propose the use of the SSpro/ACCpro 5 methods to predict protein secondary structure and relative solvent accessibility [13] . By comparing the prediction results obtained on the reference genome and mutated genomes, we are able to assess whether the detected mutations have the potential to change the protein structure and solvent accessibility, and thus lead to possible changes of the virus characteristics. cache = ./cache/cord-255371-o9oxchq6.txt txt = ./txt/cord-255371-o9oxchq6.txt === reduce.pl bib === id = cord-259261-fmuozy3w author = Bickler, Stephen W. title = AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE date = 2020-06-16 pages = extension = .txt mime = text/plain words = 2039 sentences = 130 flesch = 55 summary = title: AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. We also asked the question if the differentially expressed genes between the oldest and youngest age groups encode proteins that interact with SARS-CoV-2 (see "Methods" section). Our analysis revealed eleven differentially expressed genes between the oldest and youngest age groups that encode proteins known to interact with SARS-CoV-2 (Fig. 3d) . Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts we show that expression of PRR genes and ACE2, the receptor for SARS-CoV-2 vary with age. cache = ./cache/cord-259261-fmuozy3w.txt txt = ./txt/cord-259261-fmuozy3w.txt === reduce.pl bib === id = cord-255515-7se14455 author = Graudenzi, Alex title = Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity date = 2020-07-06 pages = extension = .txt mime = text/plain words = 8275 sentences = 450 flesch = 53 summary = To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, our analysis allowed to identify three non-overlapping mutational signatures, i.e., specific distributions of nucleotide substitutions, which are observed in distinct clusters of samples in a mutually exclusive fashion, suggesting the presence of host-related mutational processes. Finally, the analysis of homoplasies, i.e., (low-frequency) variants shared across distinct viral lineages and unlikely due to infection events, demonstrate that a high number of mutations can independently emerge in multiple samples, due to mutational hotspots often related to signatures or, possibly, to positive (functional) selection. cache = ./cache/cord-255515-7se14455.txt txt = ./txt/cord-255515-7se14455.txt === reduce.pl bib === id = cord-259620-qigfstxt author = Yang, Chen title = Kidney injury molecule-1 is a potential receptor for SARS-CoV-2 date = 2020-10-10 pages = extension = .txt mime = text/plain words = 3373 sentences = 205 flesch = 54 summary = Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Studies have indicated direct infection of SARS-CoV-2 in kidney in addition to lung 5, 31 , however, ACE2 remains the only confirmed receptor which may mediate this invasion. Notably, our results suggest that SARS-CoV-2-RBD binds KIM1 and ACE2 via two distinct pockets, implicating that KIM1 and ACE2 may synergistically mediate the invasion of SARS-CoV-2 in kidney cells; which may explain the strong renal tropism, as well as the high incidence of acute kidney injury in COVID-19 patients 5 . ACE2 is the most well-studied receptor for SARS-CoV-2 so far, yet it is not an ideal therapeutic target for COVID-19 since it is widely expresses in multiple organs, and plays crucial roles in regulating blood pressure and preventing heart/kidney injury 36, 37 . cache = ./cache/cord-259620-qigfstxt.txt txt = ./txt/cord-259620-qigfstxt.txt === reduce.pl bib === id = cord-255888-znfgh78m author = Fisher, Dale title = Seeding of outbreaks of COVID-19 by contaminated fresh and frozen food date = 2020-08-18 pages = extension = .txt mime = text/plain words = 1816 sentences = 110 flesch = 58 summary = SARS-CoV-2 was detected on workers and environmental samples, including a cutting board used to slice imported salmon. We have assessed the survival of SARS-CoV-2 on refrigerated and frozen meat and salmon over 3 weeks to assess the potential of outbreaks being seeded by imported contaminated food. The clusters of infection of COVID-19 among workers in slaughterhouses and meat processing facilities in many countries can be attributed to factors that promote transmission of virus directly between workers, such as crowding, poor ventilation, and shouting in close proximity due to high ambient noise levels. With a significant burden of virus present in infected workers and the environment then contamination of meat with SARS-CoV-2 is possible during butchering and processing. Our laboratory work has shown that SARS-CoV-2 can survive the time and temperatures associated with transportation and storage conditions associated with international food trade. We believe it is possible that contaminated imported food can transfer virus to workers as well as the environment. cache = ./cache/cord-255888-znfgh78m.txt txt = ./txt/cord-255888-znfgh78m.txt === reduce.pl bib === id = cord-261961-u4d0vvmq author = St-Germain, Jonathan R. title = A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research date = 2020-08-28 pages = extension = .txt mime = text/plain words = 2735 sentences = 147 flesch = 41 summary = To this end, we conducted a mass spectrometry-based characterization of the SARS-CoV-2 virion and infected cell lysates, identifying 189 unique high-confidence virus tryptic peptides derived from 17 different virus proteins, to create a high quality resource for use in targeted proteomics approaches. The resulting viral tryptic peptides were identified using nanoflow liquid chromatography -tandem mass spectrometry (LC-MS/MS; Fig 1A, Together, these data confirm and expand upon previous proteomic analyses of SARS-CoV-2 virions, infected cells 4, 7-11 and patient samples [12] [13] [14] , and provide a library of high quality virus peptide spectra covering 17 virus proteins that can be used for the creation of peptide spectral libraries and targeted proteomics approaches. To this end, we also undertook an analysis of SARS-CoV-2 virions and infected Vero cell lsyates using data-dependent acquisition tandem mass spectrometry, and identified 189 unique tryptic peptides, assigned to 17 different virus proteins. cache = ./cache/cord-261961-u4d0vvmq.txt txt = ./txt/cord-261961-u4d0vvmq.txt === reduce.pl bib === id = cord-262145-i29e3fge author = Huang, Kuan-Ying A. title = Breadth and function of antibody response to acute SARS-CoV-2 infection in humans date = 2020-10-19 pages = extension = .txt mime = text/plain words = 2949 sentences = 207 flesch = 61 summary = A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. The MAbs with 161 strong anti-RBD binding have a relatively long heavy chain CDR3 length (50% 162 binding concentration <0.5 µg/ml versus >0.5 µg/ml, p=0.03, two-tailed Mann-163 Whitney test; Supplemental Figure 3 The 32 anti-spike glycoprotein MAbs were systematically examined by plaque 173 reduction neutralisation (PRNT) assay for neutralisation of wild type SARS-CoV-2 174 virus (see methods; summarised in Table 1 ). Potent neutralising antibodies to the RBD of SARS-CoV-2 spike glycoprotein were 188 identified and we thus analyse the blockade of the ACE2-RBD interaction by anti-189 RBD antibodies in two assays ( Figure 3 , Table 1 The structure of VHH72-Fc bound to RBD is known (17) and its footprint on the 198 RBD does not overlap that of ACE2, so inhibition is thought to occur by steric 199 hindrance. cache = ./cache/cord-262145-i29e3fge.txt txt = ./txt/cord-262145-i29e3fge.txt === reduce.pl bib === id = cord-258650-aeyf0yu1 author = Joshi, Bhrugesh title = deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 date = 2020-04-02 pages = extension = .txt mime = text/plain words = 1995 sentences = 98 flesch = 52 summary = title: deepMINE Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 In the demanding situation of COVID-19, we applied the literature mining with user entered keyword(s) and automatic generation of brief summary of research articles, that user searches for. The deepMINE is primarily performing two major functions namely mining of articles from available open data sources using user-entered keywords and generate brief technical summary in natural language for a quick review of articles that user interested with. The system has used the deep natural language processing-based text summarization for generating detailed technical summary given the research article as an input. Our system deepMINE is providing mining from 29,315 research articles with keywords by scanning nearly 1,46,115,136 English words available in literature dataset in not greater than 1.5 seconds. cache = ./cache/cord-258650-aeyf0yu1.txt txt = ./txt/cord-258650-aeyf0yu1.txt === reduce.pl bib === id = cord-255895-6at9gelt author = Han, Namshik title = Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies date = 2020-08-25 pages = extension = .txt mime = text/plain words = 4736 sentences = 269 flesch = 52 summary = We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by COVID-19 multi-omic datasets(Bojkova et al., 2020; Gordon et al., 2020), and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials(Clinicaltrials.gov, 2020) testifying to the validity of the approach. Importantly, treatment of Calu-3 and Vero E6 cell lines with Proguanil and Sulfasalazine led to a significant downregulation of the mRNA of key cytokines (Figures 4G-J and S8), which are dictated by the p38/MAPK signalling pathway and shown to become elevated during SARS-CoV-2 infection and replication (CXCL3, IFNB1 and TNF-A). Here we have used a series of computational approaches, including bespoke methods for data integration, network analysis, computer simulation and machine learning, to identify novel SARS-CoV-2 induced pathways that could be targeted therapeutically by repurposing existing and approved drugs ( Figure S9 ). cache = ./cache/cord-255895-6at9gelt.txt txt = ./txt/cord-255895-6at9gelt.txt === reduce.pl bib === id = cord-262602-on0w55x0 author = Muruato, Antonio E. title = A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation date = 2020-05-22 pages = extension = .txt mime = text/plain words = 880 sentences = 53 flesch = 53 summary = Therefore, a high-throughput assay to measure SARS-CoV-2 neutralizing antibodies is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, and vaccine development. Here we report on a fluorescence-based SARS-CoV-2 neutralization assay that detects SARS-CoV-2 neutralizing antibodies in COVID-19 patient specimens and yields comparable results to plaque reduction neutralizing assay, the gold standard of serological testing. To validate the reporter virus neutralization results, we performed the conventional 6 4 PRNT on the same set of patient specimens. The results demonstrate that when diagnosing 6 8 patient specimens, the reporter virus assay delivers neutralization results comparable to the 6 9 PRNT assay, the gold standard of serological testing. Next, we evaluated the specificity of reporter neutralization assay using potentially cross-7 1 reactive sera and interfering substances (Table 1) . Nevertheless, the 1 0 3 mNeonGreen reporter assay offers a rapid, high-throughput platform to test COVID-19 patient 1 0 4 sera not previously available. cache = ./cache/cord-262602-on0w55x0.txt txt = ./txt/cord-262602-on0w55x0.txt === reduce.pl bib === === reduce.pl bib === id = cord-259340-1ir19s25 author = Das, Rohit Pritam title = Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach date = 2020-07-01 pages = extension = .txt mime = text/plain words = 1640 sentences = 128 flesch = 51 summary = Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The B-cell epitopic regions present in SARS-CoV-2 S protein were identified using BcePred prediction server (https://webs.iiitd.edu.in/cgibin/bcepred/) [17] . Molecular docking was performed between the predicted peptides and MHC representative structures using PatchDock web server [22, 23, 24] . Interaction of both TLR2 and TLR4 structures with the predicted peptides were performed using PatchDock web server [22, 23, 24] . This study is focused on the prediction of effective epitopes from Spike protein of SARS-CoV-2. cache = ./cache/cord-259340-1ir19s25.txt txt = ./txt/cord-259340-1ir19s25.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-260054-iihgc5nr author = Cavallo, Luigi title = D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly date = 2020-06-08 pages = extension = .txt mime = text/plain words = 4062 sentences = 210 flesch = 59 summary = 3D structures are now available from the Protein Data Bank (PDB) (21) for the SARS-CoV-2 S protein in the pre-fusion conformation, also bound to the ACE2 receptor (22) (23) (24) (25) (26) (27) (28) , and for the post-fusion core of its S2 subunit in the postfusion conformation (29) . We downloaded all the SARS-CoV-2 genomic sequences from the GISAID resource on April 21 st 2020, extracted from them 7,692 complete S protein sequences and identified all the point mutations occurring in at least two identical sequences (see Methods). When looking at the post-fusion conformation of the SARS-CoV-2 spike protein S2 subunit, these mutations appear more revealing. Based on a thorough analysis of the S protein sequences, that we extracted from the genomic sequences of SARS-CoV-2 reported in GISAID on April 21 st , we identified the fusion core of the HR1 as a mutational hotspot. cache = ./cache/cord-260054-iihgc5nr.txt txt = ./txt/cord-260054-iihgc5nr.txt === reduce.pl bib === id = cord-261718-zqoggwnk author = Pietschmann, Jan title = Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date = 2020-06-03 pages = extension = .txt mime = text/plain words = 1188 sentences = 76 flesch = 45 summary = Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. After addition of 176 biotinylated GaR and subsequent labelling with streptavidin-AP, the ELISA plate was read out at 177 405 nm and obtained measuring values were used to generate calibration curves for SARS-CoV-2 178 specific antibody concentrations in PBS (Fig 1, black curve) and in human serum samples (Fig 1, red 179 curve). Same calibration measurements employing dilutions of SARS-CoV-2 specific antibody were 211 done with our PoC MInD-based setup (Fig 2 and 3) . Comparable to laboratory-based ELISA, the same 212 dilutions of SARS-CoV-2 spike protein peptide specific antibody in PBS-buffer (Fig 3, black cache = ./cache/cord-261718-zqoggwnk.txt txt = ./txt/cord-261718-zqoggwnk.txt === reduce.pl bib === === reduce.pl bib === id = cord-260352-rhd0qqyn author = Bhattacharyya, Sumit title = Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity date = 2020-06-25 pages = extension = .txt mime = text/plain words = 2739 sentences = 162 flesch = 50 summary = CHST15 (N-acetylgalactosamine 4ARSB activation requires oxygen for post-translational modification and activation, and ARSB activity is lower in hypoxic conditions [12, 13] ; b) decline in ARSB is associated with increased IL-6 expression in human bronchial epithelial cells and in patients with cystic fibrosis and asthma [14] ; c) decline in ARSB replicates effects of hypoxia and generation of sulfate by ARSB may be important in mitochondrial metabolism [12, 15] ; d) accumulation of sulfated glycosaminoglycans when ARSB is reduced can contribute to inflammation and pulmonary pathophysiology, as in cystic fibrosis [16] ; e) in patients with moderate COPD, refractoriness to oxygen therapy was associated with gene mutations regulating ARSB expression [17] ; and f) changes in chondroitin 4-sulfation affect binding of the critical molecules galectin-3 and SHP2 (PTPN11; protein tyrosine phosphatase non-receptor type 11) with impact on transcriptional events and vital cell signaling [18, 19] . cache = ./cache/cord-260352-rhd0qqyn.txt txt = ./txt/cord-260352-rhd0qqyn.txt === reduce.pl bib === id = cord-261688-njlxrxv6 author = Yang, Ziwei title = Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2 date = 2020-08-12 pages = extension = .txt mime = text/plain words = 2508 sentences = 166 flesch = 52 summary = Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. Here, we revealed that NSP8 protein of SARS-CoV-2 directly blocks the activation of the cytosolic viral dsRNA sensor MDA5 and significantly downregulates antiviral immune responses. Our study contributes to our understanding of the direct immune evasion mechanism of SARS-CoV-2 by showing that NSP8 suppresses the most upstream sensor of innate immune responses involved in the recognition of viral dsRNA. Based on our existing experimental data, we propose a simple working model to illustrate how NSP8 218 negatively regulates innate immune responses by inhibiting MDA5 K63-linked polyubiquitination (Fig.5c) . cache = ./cache/cord-261688-njlxrxv6.txt txt = ./txt/cord-261688-njlxrxv6.txt === reduce.pl bib === === reduce.pl bib === id = cord-262958-tmp6yxlv author = Pinto, Dora title = Structural and functional analysis of a potent sarbecovirus neutralizing antibody date = 2020-04-09 pages = extension = .txt mime = text/plain words = 2241 sentences = 147 flesch = 55 summary = The SARS-CoV-2 spike (S) glycoprotein 26 promotes entry into host cells and is the main target of neutralizing antibodies. None of the mAbs studied bound to 97 prefusion OC43 S or MERS-CoV S ectodomain trimers, indicating a lack of cross-98 reactivity outside the sarbecovirus subgenus (Extended Data Fig.1) . The structural data explain the S309 cross-reactivity between SARS-CoV-2 and 148 SARS-CoV as 19 out of 24 residues of the epitope are strictly conserved ( Fig. 2f and 149 Extended Data Fig. 6a To further investigate the mechanism of S309-mediated neutralization, we 175 compared side-by-side transduction of SARS-CoV-2-MLV in the presence of either 176 S309 Fab or S309 IgG. This analysis 208 identified at least four antigenic sites within the S B domain of SARS-CoV targeted by 209 our panel of mAbs. The receptor-binding motif, which is targeted by S230, S227 and 210 S110, is termed site I. cache = ./cache/cord-262958-tmp6yxlv.txt txt = ./txt/cord-262958-tmp6yxlv.txt === reduce.pl bib === === reduce.pl bib === id = cord-260315-uau554jj author = Ramirez, Santseharay title = Efficient culture of SARS-CoV-2 in human hepatoma cells enhances viability of the virus in human lung cancer cell lines permitting the screening of antiviral compounds date = 2020-10-04 pages = extension = .txt mime = text/plain words = 2269 sentences = 122 flesch = 54 summary = title: Efficient culture of SARS-CoV-2 in human hepatoma cells enhances viability of the virus in human lung cancer cell lines permitting the screening of antiviral compounds Culture adaptation in Huh7.5 cells further permitted efficient infection of the otherwise SARS-CoV-2 refractory human lung cancer cell line A549, with titers of ~6 Log10TCID50/mL. Importance The cell culture adapted variant of the SARS-CoV-2 virus obtained in the present study, showed significantly enhanced replication and propagation in various human cell lines, including lung derived cells otherwise refractory for infection with the original virus. Further, as shown here with the use of remdesivir and EIDD-2801, two nucs with significant inhibitory effect against SARS-CoV-2, large differences in the antiviral activity are observed depending on the cell line. 137 We performed a comparative titration in various cells of the P2 VeroE6 and the P5 Huh7.5 viruses ( Figure 138 1b) and found that the infectivity titers in Huh7.5 cells after culture adaptation had increased by more 139 than 3 logs (mean of 4.7 and 8.0 Log 10 TCID 50 /mL, respectively). cache = ./cache/cord-260315-uau554jj.txt txt = ./txt/cord-260315-uau554jj.txt === reduce.pl bib === === reduce.pl bib === id = cord-255997-oer5lxxr author = Onodi, Fanny title = SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date = 2020-07-10 pages = extension = .txt mime = text/plain words = 4209 sentences = 254 flesch = 53 summary = Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . cache = ./cache/cord-255997-oer5lxxr.txt txt = ./txt/cord-255997-oer5lxxr.txt === reduce.pl bib === id = cord-261662-d0tg9i90 author = Andres, Cristina title = Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients date = 2020-06-08 pages = extension = .txt mime = text/plain words = 4673 sentences = 214 flesch = 52 summary = title: Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. Because of the importance of the S protein, we carried out a deep-sequencing study of the S gene in upper respiratory tract samples from 18 patients with mild or severe SARS-CoV-2 disease. The fact that the truncated S protein was present in only a low percentage of the entire viral quasispecies suggests that natural selection may have designed a favorable equilibrium in which a limited number of deleted virions are generated to balance virus production with infection of new cells during disease progression. cache = ./cache/cord-261662-d0tg9i90.txt txt = ./txt/cord-261662-d0tg9i90.txt === reduce.pl bib === id = cord-259084-lwh3rww4 author = Anderson, Cole title = Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2 date = 2020-05-22 pages = extension = .txt mime = text/plain words = 1002 sentences = 66 flesch = 52 summary = title: Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2 Current diagnosis of COVID-19 relies on the detection of SARS-CoV-2 RNA by RT-PCR in upper and lower respiratory specimens. Implementing a pooling strategy can significantly increase laboratory testing capacity while simultaneously reducing turnaround times for rapid identification and isolation of positive COVID-19 cases in high risk populations. This protocol allows for 35 the rapid detection of SARS-CoV-2 RNA from clinical specimens such as, nasopharyngeal and 36 oropharyngeal swabs, sputum, bronchoalveolar lavage, and tracheal aspirates. 43 In this study, we examined the feasibility of pooling nasopharyngeal swab specimens submitted 44 for COVID-19 testing using the CDC 2019-nCoV RT-PCR diagnostic panel without compromising 45 Specimens were submitted to 54 the Virology laboratory at Landstuhl Regional Medical Center for routine SARS-CoV-2 testing 55 using the CDC 2019-nCoV RT-PCR assay. Pooling nasopharyngeal/throat swab specimens to increase testing 176 capacity for influenza viruses by PCR cache = ./cache/cord-259084-lwh3rww4.txt txt = ./txt/cord-259084-lwh3rww4.txt === reduce.pl bib === id = cord-262573-wdgbno9p author = Begum, Feroza title = Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India date = 2020-05-03 pages = extension = .txt mime = text/plain words = 1615 sentences = 96 flesch = 60 summary = We report one unique mutation at position 723 and the other at 1124 in the S2 domain of spike protein of the isolates from West Bengal only and one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western part of India). We downloaded the five new SARS-CoV2 sequences from West Bengal (EPI_ISL_430468; EPI_ISL_430467; EPI_ISL_430465; EPI_ISL_430464; EPI_ISL_430466) from GISAID database and the spike protein sequences corresponding to Kerala isolates [2] and Gujarat isolate [3] from the NCBI virus database. Since, currently we have sequences against SARS-CoV2 only from three states in India i.e. Kerala, Gujarat and now West Bengal, we compared all the sequences to detect possible changes ( Figure 2) . This is the first report of mutations of such types in the isolates of the state of West Bengal and further sequencing followed by sequence analyses would help expanding the knowledge about variations of spike protein in human SARS-CoV. cache = ./cache/cord-262573-wdgbno9p.txt txt = ./txt/cord-262573-wdgbno9p.txt === reduce.pl bib === id = cord-264012-q2quyijg author = Lim, Su Bin title = ACE2-expressing endothelial cells in aging mouse brain date = 2020-07-11 pages = extension = .txt mime = text/plain words = 2133 sentences = 106 flesch = 48 summary = Further, scRNA-seq dataset specifically derived from brain vasculature in young adult and aged mice (T3) confirms the elevated ACE2 expression in subsets of the three identified cell types, which consist of 32.8% of the cell populations ( Fig. 1 C) . While our study provides a foundation for a more refined level of analysis of EC and vascular PC, a cell type that remains poorly understood despite its key roles in immune response and microvascular stability [17] , our analyses are limited only to the normal aging mouse and human brains, lacking the context of COVID-19 neuropathology. Despite the works that failed to identify direct signs of SARS-CoV-2 infection in the brains of COVID-19 patients [12, 13] , other lines of evidence support the neurotropism of the virus, as evidenced by experimental platforms leveraging human induced pluripotent stem cell (iPSC)derived dopaminergic neurons [22] and an organotypic brain model [23] . cache = ./cache/cord-264012-q2quyijg.txt txt = ./txt/cord-264012-q2quyijg.txt === reduce.pl bib === id = cord-262485-sx2q5ol4 author = Davda, Jayeshkumar Narsibhai title = An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance date = 2020-06-08 pages = extension = .txt mime = text/plain words = 3255 sentences = 193 flesch = 59 summary = The method employs real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) of RNA extracted from nasopharyngeal (NP) swab samples, to measure amplification of a short segment of a viral gene in the course of a PCR reaction following reverse transcription of viral RNA. We developed and tested a RT-nPCR protocol comprising a multiplex primary RT-PCR for amplification of four SARS-CoV-2 amplicons and a control human RPP30 amplicon followed by a secondary nested PCR for individual amplicons 4 and visualization by agarose gel electrophoresis. Based on the experimentally measured false negative rate by RT-nPCR tests from this study we estimated that as many as 50% of positive samples may escape detection in single pass testing by RT-qPCR in an actual testing scenario. To detect the presence of SARS-CoV-2 in RNA isolated from NP swabs we performed a multiplex one-step RT-PCR on RNA from positive and negative samples using pooled primers for the four viral amplicons together with human RPP30 control. cache = ./cache/cord-262485-sx2q5ol4.txt txt = ./txt/cord-262485-sx2q5ol4.txt === reduce.pl bib === id = cord-262470-nkql7h9x author = Muus, Christoph title = Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells date = 2020-04-20 pages = extension = .txt mime = text/plain words = 17577 sentences = 869 flesch = 50 summary = title: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. To assess the association of age, sex, and smoking status with the expression of ACE2, TMPRSS2, and CTSL, we aggregated 22 scRNA-seq datasets of healthy human nasal and lung cells, as well as fetal samples. cache = ./cache/cord-262470-nkql7h9x.txt txt = ./txt/cord-262470-nkql7h9x.txt === reduce.pl bib === id = cord-261855-qpbgq5d8 author = Walker, Susanne N. title = SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients date = 2020-06-18 pages = extension = .txt mime = text/plain words = 2533 sentences = 166 flesch = 57 summary = title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients. Here, we describe a competition ELISA assay and a SPR 100 assay developed to rapidly detect ACE2 receptor blocking antibodies in IgGs and sera of 101 vaccinated mice, guinea pigs, rabbits and non-human primates, as well as, human samples (Fig. 1B) . Next, using Enzyme-Linked Immunosorbent Assays (ELISAs) we immobilized full-length 120 SARS-CoV-2 spike protein (containing both the S1 and S2 subunits) and incubated a dilution 121 series of ACE2-IgHu (Fig. 1D) . The proof-of-concept competition ELISA displayed a full blocking curve, so we sought to utilize 140 this assay for animals immunized with SARS-CoV-2 spike protein. cache = ./cache/cord-261855-qpbgq5d8.txt txt = ./txt/cord-261855-qpbgq5d8.txt === reduce.pl bib === id = cord-263594-jd9ako6c author = Kang, Sisi title = A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation date = 2020-09-11 pages = extension = .txt mime = text/plain words = 2517 sentences = 181 flesch = 56 summary = Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Severe acute 57 respiratory distress syndrome-associated coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein 58 is a highly immunopathogenic and multifunctional viral protein (14) (15) (16) (17) (18) (19) , which elicited high titers 59 of binding antibodies in humoral immune responses (20) (21) (22) . Herein, 66 we report a human mAb derived from COVID-19 convalescent, with specific targeting to SARS-67 CoV-2 N protein and functionally compromising complement hyper-activation ex vivo. Isolation of N protein-directed mAbs 69 To profile antibody response to SARS-CoV-2 N protein in early recovered patients, we collected 70 six convalescent blood samples at seven to 25 days after the onset of the disease symptoms. cache = ./cache/cord-263594-jd9ako6c.txt txt = ./txt/cord-263594-jd9ako6c.txt === reduce.pl bib === id = cord-262119-s6hc7fxs author = Ostaszewski, Marek title = COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date = 2020-10-27 pages = extension = .txt mime = text/plain words = 12332 sentences = 742 flesch = 38 summary = title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms cache = ./cache/cord-262119-s6hc7fxs.txt txt = ./txt/cord-262119-s6hc7fxs.txt === reduce.pl bib === id = cord-264031-0y7xbgun author = Wierbowski, Shayne D. title = A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date = 2020-10-13 pages = extension = .txt mime = text/plain words = 5066 sentences = 291 flesch = 42 summary = title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. cache = ./cache/cord-264031-0y7xbgun.txt txt = ./txt/cord-264031-0y7xbgun.txt === reduce.pl bib === id = cord-267115-6jqdi417 author = Giobbe, Giovanni Giuseppe title = SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date = 2020-06-24 pages = extension = .txt mime = text/plain words = 8080 sentences = 408 flesch = 47 summary = Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. Principal component analysis (PCA) showed smaller heterogeneity in the organoid groups derived at different stages of fetal and pediatric development with respect to the primary tissues analyzed at the same stages, which may also include some heterogeneity from the surrounding cells as a result of the isolation procedure (Fig. 3a) . In order to validate both fetal and pediatric gastric organoids as functional in vitro models of SARS-CoV-2 infection and replication, we optimized the culture condition for viral infection in a 3D system (Fig. 4a) . cache = ./cache/cord-267115-6jqdi417.txt txt = ./txt/cord-267115-6jqdi417.txt === reduce.pl bib === id = cord-265453-z6aux01t author = Bierig, Tobias title = Design, expression, purification and characterization of a YFP-tagged 2019-nCoV spike receptor-binding domain construct date = 2020-09-29 pages = extension = .txt mime = text/plain words = 3438 sentences = 183 flesch = 58 summary = The receptor-binding domain (RBD) of the 2019-nCoV spike (S) protein contains disulfide bonds and N-linked glycosylations, therefore, it is typically produced by secretion. Here, we describe a construct and protocol for the expression and purification of yellow fluorescent protein (YFP) labeled 2019-nCoV spike RBD. The fusion protein, in the vector pcDNA 4/TO, comprises an N-terminal interferon alpha 2 (IFNα2) signal peptide, an eYFP, a FLAG-tag, a human rhinovirus 3C protease cleavage site, the RBD of the 2019-nCoV spike protein and a C-terminal 8x His-tag. Our experiments confirmed that the fusion protein (also after proteolytic removal of YFP) binds the human ACE2 peptidase domain. Ni-NTA IMAC After removal of detached cells by centrifugation, the expression medium containing the secreted fusion protein was supplemented with 1/4 tablet of protease inhibitor (complete EDTA-free protease inhibitor cocktail tablets, Roche Diagnostic GmbH, 45148300) and transferred to a 15 ml Falcon tube containing 200 l of washed, pre-equilibrated Ni-NTA agarose (Qiagen Cat. No. cache = ./cache/cord-265453-z6aux01t.txt txt = ./txt/cord-265453-z6aux01t.txt === reduce.pl bib === id = cord-263780-8jejswuk author = Wang, Nan title = Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus date = 2020-08-14 pages = extension = .txt mime = text/plain words = 1584 sentences = 103 flesch = 66 summary = title: Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus Purpose The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. Conclusions CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. In this study, we found that CQ and HCQ can antagonize ACE2 and inhibit the entry of 2019-nCoV 103 spike pseudotyped virus into ACE2 expressed HEK293T cells (ACE2 h cells). It can be concluded that the toxicity 216 of HCQ was higher than that of CQ on ACE2 h cells at different time points at the same 217 concentrations (Figure 1C) . cache = ./cache/cord-263780-8jejswuk.txt txt = ./txt/cord-263780-8jejswuk.txt === reduce.pl bib === id = cord-267613-hsc2x36j author = Dittmar, Mark title = Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2 date = 2020-06-19 pages = extension = .txt mime = text/plain words = 7558 sentences = 452 flesch = 50 summary = Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. Previous studies found that the antiviral drug remdesivir, which was developed against the RNA-dependent RNA polymerase of Ebola virus, was also active against SARS-CoV-2 in vitro, with promising results in clinical trials (5) (6) (7) . Both cepharanthine and tetrandrine were previously shown to have antiviral activity against the human coronavirus OC43 and in recent studies on SARS-CoV-2 in Vero cell screens (13, 62, 63) . Strikingly, the activities of all of these drugs is similar in the two cell lines suggesting the same target and mechanism-of-action and that Cyclosporine would block SARS-CoV-2 in diverse infected tissues in vivo. cache = ./cache/cord-267613-hsc2x36j.txt txt = ./txt/cord-267613-hsc2x36j.txt === reduce.pl bib === id = cord-263970-9w6ciglv author = Marquez-Miranda, Valeria title = Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites date = 2020-10-22 pages = extension = .txt mime = text/plain words = 2882 sentences = 166 flesch = 53 summary = SARS-CoV-2 ORF3a is believed to form ion channels, which may be involved in the modulation of virus release, and has been implicated in various cellular processes like the up-regulation of fibrinogen expression in lung epithelial cells, downregulation of type 1 interferon receptor, caspase-dependent apoptosis, and increasing IFNAR1 ubiquitination. Here we used this dimeric structure to perform full atom molecular dynamic simulations and electrostatic potential calculations to ask questions concerning the dimers' stability and whether ions could be populating specific regions of the channel. To assess the impact of the ion occupancies described above, we obtained the electrostatic potential maps for the ORF3a channel for the initial configuration, and the last frame, at the end of a trajectory of 500 ns of the molecular dynamics simulations, by employing the Poison-Boltzmann approach implemented in the APBS package [12] . This analysis shows that the entry of Cl-ions through the inter-subunit tunnel into the central polar cavity and the accumulation of K+ ions at the cytosolic domain's surface changed the channel's electrostatic profile. cache = ./cache/cord-263970-9w6ciglv.txt txt = ./txt/cord-263970-9w6ciglv.txt === reduce.pl bib === id = cord-264204-4ablrwuo author = Guintivano, Jerry title = Psychiatric Genomics Research During the COVID-19 Pandemic: A Survey of Psychiatric Genomics Consortium Researchers date = 2020-10-08 pages = extension = .txt mime = text/plain words = 3998 sentences = 159 flesch = 43 summary = We provide recommendations for institutions, organizations such as the PGC, as well as individual senior investigators to ensure that the futures of early career investigators, especially those underrepresented in academic medicine such as women and underrepresented minorities, are not disproportionately disadvantaged by the COVID-19 pandemic. Four main themes characterized the comments: maintain team dynamics (e.g., utilizing videoconferencing for regular team meetings, being flexible with deadlines, use clear communication) (32.8% of responses); maintain good personal habits (e.g., keeping in mind productivity may be reduced, practicing self-care, keeping work and personal areas separate) (27.2%); reprioritize research goals (e.g., spending more effort on dry-lab projects rather than wet-lab, using available time to complete analyses or manuscripts, utilizing existing data for new projects) (20.8%); and shift recruitment to online approaches (e.g., phone interviews rather than face-to-face, development of online recruitment and consent protocols) (8.0%). cache = ./cache/cord-264204-4ablrwuo.txt txt = ./txt/cord-264204-4ablrwuo.txt === reduce.pl bib === id = cord-266444-rw94yls8 author = Dominguez Andres, Ana title = SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date = 2020-08-19 pages = extension = .txt mime = text/plain words = 5639 sentences = 305 flesch = 44 summary = The interactome and proteome studies identified cellular processes affected by SARS-CoV-2 infection or specific viral proteins, notably innate immune signaling (19, 20, 23, (28) (29) (30) , ubiquitin ligase activities (19, 20, 23, (28) (29) (30) , p38 mitogenactivated protein kinase (MAPK) signaling (19, 20, 23, (28) (29) (30) . To assess if there were notable differences in the intensity of the changes in protein abundance in response to proteasome inhibition, we calculated relative changes in protein abundance between control and ORF9c-expressing cells from both the DMSO and MG132 conditions for proteins associated with IFN signaling or the ubiquitin proteasome (UBP) system and antigen presentation (Fig. 2D ). In contrast to the proteomic results that revealed predominant downregulation of proteins following ORF9c expression, RNA-seq analysis showed a similar number of transcripts were increased or decreased in the presence or absence of MG132 (Fig. 3A, table S2 ). cache = ./cache/cord-266444-rw94yls8.txt txt = ./txt/cord-266444-rw94yls8.txt === reduce.pl bib === id = cord-263008-w6twrjzr author = Yin, Rui title = Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide date = 2020-07-15 pages = extension = .txt mime = text/plain words = 3684 sentences = 213 flesch = 48 summary = title: Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide We developed alignment-free machine learning approaches for an ultra-fast and highly accurate prediction of the lethality of potential human-adapted coronavirus using genomic nucleotide. We performed extensive experiments through six different feature transformation and machine learning algorithms in combination with digital signal processing to infer the lethality of possible future novel coronaviruses using previous existing strains. The results demonstrate that, for any novel human coronavirus strains, this alignment-free machine learning-based approach can offer a reliable real-time estimation for its viral lethality. In this paper, we propose alignment-free machine learning-based approaches to infer 81 2/18 the lethality of potential novel human-adapted coronavirus using genomic sequences. We provide a comprehensive analysis through alignment-free machine learning-based 385 methods for the prediction of the lethality of potential human-adapted coronavirus. cache = ./cache/cord-263008-w6twrjzr.txt txt = ./txt/cord-263008-w6twrjzr.txt === reduce.pl bib === id = cord-265418-yqe9vdj1 author = Kumar, Nilesh title = Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis date = 2020-04-11 pages = extension = .txt mime = text/plain words = 5288 sentences = 363 flesch = 54 summary = Integrated interactome-transcriptome analysis to generate Calu-3-specific humanIt is likely that the outcome of SARS-CoV-2 infection can largely be determined by the interaction patterns of host proteins and viral factors. By integrating this Calu-3 co-expression network with SIPs-derived PPI subnetwork, we generated Calu-3-specific human-SARS-CoV-2 Interactome (CSI) that contains 214 SIPs interacting with their first and second neighbors make a network of 4,123 nodes and 14,650 edges (Fig. 1c, Supplementary Data 1) . We showed that CSI follows a power law degree distribution with a few nodes harboring increased connectivity, and thus exhibits properties of a scale-free network (r 2 = 0.91; (Fig. 1d , Supplementary Data 1), similar to the previously generated other human-viral interactomes 12, 13, 14, 15, 16, 17, 18, 19, 20, 24, 25, 26, 27, 28 . In conclusion, we generated a human-SARS-CoV-2 interactome, integrated virusrelated transcriptome to interactome, discover COVID-19 pertinent structural and functional modules, identify high-value viral targets, and perform dynamic transcriptional modeling. cache = ./cache/cord-265418-yqe9vdj1.txt txt = ./txt/cord-265418-yqe9vdj1.txt === reduce.pl bib === id = cord-266869-fs8dn7ir author = Kim, So Young title = Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry date = 2020-04-15 pages = extension = .txt mime = text/plain words = 3813 sentences = 217 flesch = 54 summary = title: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Using a modified version of Autodock Vina tuned for use with carbohydrates (Vina-Carb) [20, 21] , we performed blind docking on the trimeric SARS-CoV-2 SGP model to discover objectively the preferred binding GAG-binding sites on the SGP protein surface. cache = ./cache/cord-266869-fs8dn7ir.txt txt = ./txt/cord-266869-fs8dn7ir.txt === reduce.pl bib === id = cord-269285-2r40mico author = Resnick, Samuel J. title = A simplified cell-based assay to identify coronavirus 3CL protease inhibitors date = 2020-08-29 pages = extension = .txt mime = text/plain words = 1941 sentences = 126 flesch = 60 summary = We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. In general, we observe concordance between compounds showing activity within 129 this transfection-based 3CL assay and live virus studies ( Supplementary Fig. 4a -e) 13 . The other hit from the 169 screen, GRL-0496, shares structural similarity to several other compounds within the library, one of 170 which is a previously reported 3CLpro inhibitor (MAC-5576) that failed to show activity against 5.05 µM against SARS-CoV-2 3CLpro within our transfection-based assay (Fig. 4c ). . https://doi.org/10.1101/2020.08.29.272864 doi: bioRxiv preprint we propose that this cellular protease assay system could be industrialized to screen and optimize a 219 large number of compounds to discover potential treatments for future viral pandemics. cache = ./cache/cord-269285-2r40mico.txt txt = ./txt/cord-269285-2r40mico.txt === reduce.pl bib === id = cord-267223-pf799wbw author = de Lamballerie, Claire Nicolas title = Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection in a human airway epithelial model date = 2020-05-19 pages = extension = .txt mime = text/plain words = 1182 sentences = 75 flesch = 31 summary = An increasing number of evidence indicate a relatively high prevalence of superinfections associated with COVID-19, including invasive aspergillosis, but the underlying mechanisms remain to be characterized. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyteand neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis in this specific context. Our results also highlight unique transcriptional 30 footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, 31 and an induction of several monocyte-and neutrophil associated chemokines, that could be 32 useful for the understanding of Aspergillus-associated COVID-19 and but also management 33 of severe forms of aspergillosis in this specific context. cache = ./cache/cord-267223-pf799wbw.txt txt = ./txt/cord-267223-pf799wbw.txt === reduce.pl bib === id = cord-267482-afqfymbq author = Ryu, Seungjin title = Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model date = 2020-09-12 pages = extension = .txt mime = text/plain words = 8189 sentences = 476 flesch = 49 summary = Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Also, initial studies that employ lung ciliated epithelial cell-specific HFH4/FOXJ1 promoter driven hACE2 transgenic mice show SARS-CoV-2 infection induces weight loss, lung inflammation and approximately 50% mortality rate, suggesting the usefulness of this model to understand the mechanism of immune dysregulation (Jiang et al., 2020) . Moreover, given our recent findings that ketogenesis inhibits inflammation and expands tissue resident ϒδ T cells (Goldberg et al., 2019) while SARS-CoV-2 infection in patients is associated with depletion of ϒδ T cells (Lei et al., 2020; Rijkers et al., 2020) , we next tested whether elevating BHB by feeding a ketogenic diet (KD) protects against mCoV-A59-driven inflammatory damage in aged mice. cache = ./cache/cord-267482-afqfymbq.txt txt = ./txt/cord-267482-afqfymbq.txt === reduce.pl bib === id = cord-267536-rvhwl4ea author = Miyashita, L title = Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells date = 2020-05-27 pages = extension = .txt mime = text/plain words = 1093 sentences = 61 flesch = 57 summary = title: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells Objective To assess the effect of traffic-derived PM10 on human airway epithelial cell ACE2 expression in vitro. Conclusion Traffic-related PM10 increases the expression of the receptor for SARS-CoV-2 in human respiratory epithelial cells. Culture of A549 cells with 5% CSE, a putative positive control, increased ACE2 expression (MFI, n=4, 0 (0 to 28) vs. We also found that traffic-derived PM 10 upregulates ACE2 expression in human primary nasal epithelial cells, suggesting that this response occurs throughout the respiratory tract. First, we did not determine whether increased In conclusion, this study provides the first mechanistic evidence that traffic-derived air pollution increases ACE2 expression in human airway cells and therefore 1 3 vulnerability to SARS-CoV-2 infection. cache = ./cache/cord-267536-rvhwl4ea.txt txt = ./txt/cord-267536-rvhwl4ea.txt === reduce.pl bib === id = cord-264296-0x90yubt author = Sawmya, Shashata title = Analyzing hCov genome sequences: Applying Machine Intelligence and beyond date = 2020-06-03 pages = extension = .txt mime = text/plain words = 5008 sentences = 312 flesch = 60 summary = We present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. C. Several CNN-RNN based models are used to predict mutations at specific Sites of Interest (SoIs) of the sars-cov-2 genome sequence followed by further analyses of the same on several South-Asian countries. D. Overall, we present an analysis pipeline that can be further utilized as well as extended and revised (a) to study where a newly discovered genome sequence lies in relation to its predecessors in different regions of the world; (b) to analyse its virulence with respect to the number of deaths its predecessors have caused in their respective countries and (c) to analyse the mutation at specific important sites of the viral genome. cache = ./cache/cord-264296-0x90yubt.txt txt = ./txt/cord-264296-0x90yubt.txt === reduce.pl bib === id = cord-263090-29n9tsk9 author = Roy, Susmita title = Dynamical asymmetry exposes 2019-nCoV prefusion spike date = 2020-04-21 pages = extension = .txt mime = text/plain words = 4573 sentences = 331 flesch = 57 summary = In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. B. Side and top views of the homo-trimeric structure of SARS-CoV-2 spike protein with one RBD of the S1 subunit head rotated in the up conformation. A number of Cryo-EM structures captured the 'up' and 'down' conformations of the RBD domain of spike proteins of other coronaviruses including SARS-CoV-2 where the S1 subunit undergoes a hinge-like conformational movement prerequisite for receptor binding (Fig. 2C) (7, 8, 10, 17) . Analysis of all the simulations yields the 2-D free energy landscape of the trimeric spike protein of SARS-CoV-2 ( Fig 3B) with its all possible conformations. This generates a homo-trimeric SARS-CoV-2 spike where this initial structure has important components in terms of intra and inter-chain contacts (interaction) leading to an 'S1-head-up' and an 'S1-head-down' conformation for each protomer. cache = ./cache/cord-263090-29n9tsk9.txt txt = ./txt/cord-263090-29n9tsk9.txt === reduce.pl bib === id = cord-268894-amfv3z2y author = Nguyen-Contant, Phuong title = S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit date = 2020-07-21 pages = extension = .txt mime = text/plain words = 4632 sentences = 269 flesch = 56 summary = Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD 31 and S2 subunit, and nucleocapsid [N] ) and non-SARS-CoV-2 proteins were related to 32 measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD 31 and S2 subunit, and nucleocapsid [N] ) and non-SARS-CoV-2 proteins were related to 32 measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Approximately one-third of non-SARS-CoV-140 2-exposed subjects in the healthy donor cohort had low levels of serum IgG against the S and N 141 proteins of SARS-CoV-2, likely reflecting cross-reactivity with seasonal HCoVs ( Figure 1A ). In contrast, IgG MBCs reactive to the S proteins of the HCoVs OC43 and 229E 192 and the control proteins H1 and TTd were detected in nearly 50% or more of non-SARS-CoV-2-193 exposed subjects, consistent with the higher levels of serum IgG against these antigens ( Figure 2E -194 2H) . cache = ./cache/cord-268894-amfv3z2y.txt txt = ./txt/cord-268894-amfv3z2y.txt === reduce.pl bib === id = cord-263825-g8p2lsr0 author = Maldonado, Lucas L. title = Molecular features similarities between SARS-CoV-2, SARS, MERS and key human genes could favour the viral infections and trigger collateral effects date = 2020-06-25 pages = extension = .txt mime = text/plain words = 3430 sentences = 228 flesch = 61 summary = Since human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on host cell machinery for replication and co-evolution, we selected the genes that are highly expressed in the tissue of human lungs to perform computational studies that permit to compare their molecular features with SARS, SARS-CoV-2 and MERS genes. Furthermore, we provided a list of candidate human genes whose molecular features match those of SARS-CoV-2, SARSand MERS genes, which should be considered to be incorporated into genetic population studies to evaluate thesusceptibility to respiratory viral infections caused by these viruses. SARSand MERS genes, which should be considered to be incorporated into genetic 28 population studies to evaluate thesusceptibility to respiratory viral infections caused by 29 these viruses.The results presented here, settle the basis for further research in the field 30 of human genetics associated with the new viral infection, COVID-19, caused by 31 SARS-CoV-2 and for the development of antiviral preventive methods. cache = ./cache/cord-263825-g8p2lsr0.txt txt = ./txt/cord-263825-g8p2lsr0.txt === reduce.pl bib === id = cord-264919-0jlg2gkc author = Hopp, Marie-Thérèse title = Unravelling the debate on heme effects in COVID-19 infections date = 2020-06-12 pages = extension = .txt mime = text/plain words = 7093 sentences = 366 flesch = 49 summary = On the one hand, we examine the possibility of a direct interaction of heme with select SARS-CoV-2 proteins and specific host cell proteins by applying our webserver HeMoQuest (Paul that is based on experimental data. One of the most promising findings was the prediction of heme-binding motifs (HBMs) in the host cell proteins ACE2 and TMPRSS2. We leveraged this multimodal information to hypothesize the pathways that connect key molecules associated with SARS-CoV-2 and heme to phenotypes observed in COVID-19 patients. Here, we have investigated the possibility of a direct interaction of heme with SARS-CoV-2 surface proteins and their human counterparts ACE2 and TMPRSS2. Apart from investigating the direct impact of heme on proteins at the interface of the virus-host cell interaction, we also explored similarities between relevant pathways characterizing the respective pathologies, i.e. labile heme occurrence in hemolytic conditions and COVID-19 disease progression ( Figure 4) . cache = ./cache/cord-264919-0jlg2gkc.txt txt = ./txt/cord-264919-0jlg2gkc.txt === reduce.pl bib === id = cord-268795-tjmx6msm author = Sardar, Rahila title = Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis date = 2020-03-21 pages = extension = .txt mime = text/plain words = 2257 sentences = 128 flesch = 47 summary = title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Our analysis shows unique host-miRNAs targeting SARS-CoV2 virus genes. CELLO2GO (7)server was used to infer biological function for each protein of SARS-CoV2 genome with their localization prediction. Assembled SARS-CoV2 genomes sequences in FASTA format from India, USA, China, Italy and Nepal used for coronavirus typing tool analysis. For the phylogenetic analysis, we compared the sequences of 6 SARS-CoV2 isolates from different countries namely, Wuhan, India, Italy, USA and Nepal along with other corona virus species ( Figure 1 ). cache = ./cache/cord-268795-tjmx6msm.txt txt = ./txt/cord-268795-tjmx6msm.txt === reduce.pl bib === id = cord-268339-jxm69ndw author = Karamitros, Timokratis title = SARS-CoV-2 exhibits intra-host genomic plasticity and low-frequency polymorphic quasispecies date = 2020-03-28 pages = extension = .txt mime = text/plain words = 3755 sentences = 217 flesch = 51 summary = We analyzed NGS data derived from clinical samples of three Chinese patients infected with SARS-CoV-2, in order to identify smalland large-scale intra-host variations in the viral genome. The isolated SNVs and genomic rearrangements, reflect the intra-patient capacity of the polymorphic quasispecies, which may arise rapidly during the outbreak, allowing immunological escape of the virus, offering resistance to anti-viral drugs and affecting the sensitivity of the molecular diagnostics assays. Here, we explore intra-host genomic variants and low-frequency polymorphic quasispecies in Next Generation Sequencing (NGS) data derived from patients infected by SARS-CoV-2. The S1 subunit consists of a signal peptide and the NT and receptor binding (RB) domains, with the latter sharing only 40% amino acid identity with other SARS-related CoVs. Our analysis revealed that similarly to other genomic regions, the S1 subunit hosts many low-frequency SNVs, characterized by higher density compared to the rest of the S gene sequence (Figure 1-E) . cache = ./cache/cord-268339-jxm69ndw.txt txt = ./txt/cord-268339-jxm69ndw.txt === reduce.pl bib === id = cord-265277-ymvrserl author = Crooke, Stephen N. title = Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome date = 2020-05-14 pages = extension = .txt mime = text/plain words = 4620 sentences = 249 flesch = 52 summary = A final round of selection on the basis of HLA 197 promiscuity (i.e., predicted binding to > 3 HLA molecules) and predicted antigenicity scoring using the 198 VaxiJen 2.0 server produced a subset of five candidate peptides (four ORF1ab, one S protein) as potential 199 targets for vaccine development (Table 1) with the hypothesis that increased HLA binding promiscuity 200 meant broader population base coverage by those peptides. As selective pressures are known to introduce viral mutations that promote fitness and can lead 266 to evasion of immune responses (59, 60), we first sought to investigate the genetic similarity of all 267 reported SARS-CoV-2 clinical isolates and identify a consensus sequence for use in our epitope 268 prediction studies. An increasing number of studies have employed predictive algorithms to identify potential HLA 285 class I epitopes for SARS-CoV-2, although relatively few have comprehensively analyzed the entire viral 286 proteome. cache = ./cache/cord-265277-ymvrserl.txt txt = ./txt/cord-265277-ymvrserl.txt === reduce.pl bib === id = cord-268224-5tbb8df1 author = Di Gioacchino, Andrea title = The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 date = 2020-08-27 pages = extension = .txt mime = text/plain words = 7109 sentences = 412 flesch = 62 summary = Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven, in the N protein coding region, both by the viral codon bias and by the high value of the CpG content, leading to a loss in CpG. Finally we use a model of the viral gene evolution under human host pressure, characterized by the CpG force, to study synonymous mutations, and in particular those which change CpG content, observed since the SARS-CoV-2 entered the human population (Sec. 2.3). We first compute the global force on CpG dinucleotides for SARS-Cov-2 and a variety of other viruses from the Coronaviridae family affecting humans or other mammals (bat, pangolin), see Fig. 1a , using as null model the nucleotide usage calculated from human genome [22] (see Methods Sec. 4.2) 1 . cache = ./cache/cord-268224-5tbb8df1.txt txt = ./txt/cord-268224-5tbb8df1.txt === reduce.pl bib === id = cord-270049-54t3w94z author = Campione, Elena title = Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidences date = 2020-08-17 pages = extension = .txt mime = text/plain words = 2029 sentences = 113 flesch = 53 summary = We performed a randomized, prospective, interventional study assessing the role of oral and intra-nasal lactoferrin to treat mild-to-moderate and asymptomatic COVID-19 patients to prevent disease evolution. The antiviral activity of lactoferrin related to its binding to SARS-CoV-2 and cells and protein-protein docking methods, provided the direct recognition between lactoferrin and spike S, thus hindering the spike S attachment to the human ACE2 receptor and consequently virus entering into the cells. 222 We performed the same analysis over the evaluated human lactoferrin (hLF)-Spike complex, 223 obtaining a binding pose superimposable to that observed for the bovine protein (Fig. 5B) . Clinical trial 397 We performed a randomized, prospective, interventional study to assess the efficacy of a liposomal Blood parameters obtained at T0 in COVID-19 group and control group were compared using t-test. cache = ./cache/cord-270049-54t3w94z.txt txt = ./txt/cord-270049-54t3w94z.txt === reduce.pl bib === id = cord-267845-18hb5ndr author = Resende, Paola Cristina title = SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms date = 2020-05-01 pages = extension = .txt mime = text/plain words = 1616 sentences = 89 flesch = 48 summary = Here, we describe three protocols using a unique primer set designed to recover long reads of SARS-CoV-2 directly from total RNA extracted from clinical samples. Despite those limitations, we developed a sequencing protocol that successfully obtained whole genomes from SARS-CoV-2 positive samples referred to the National Reference laboratory at FIOCRUZ in Brazil. The tiling amplicon multiplex PCR method has been previously used for virus sequencing directly from clinical samples to obtain consensus genome sequences (3). Here, we describe three protocols using a primer set designed to sequence SARS-CoV-2 directly from total RNA extracted from clinical samples, which were initially diagnosed using real-time RT-PCR (7, 8) . Here we introduce a versatile sequencing protocol to recover the complete SARS-CoV-2 genome based on reverse transcription plus an overlapping long amplicon multiplex PCR strategy, and associated with pipelines to report the data, and recover the consensus files. Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples cache = ./cache/cord-267845-18hb5ndr.txt txt = ./txt/cord-267845-18hb5ndr.txt === reduce.pl bib === id = cord-270550-if748w2n author = Bailey, Adam L. title = SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date = 2020-11-05 pages = extension = .txt mime = text/plain words = 5808 sentences = 440 flesch = 49 summary = To ascertain whether human pluripotent stem cell-derived cardiomyocytes (hPSC-derived 150 CMs) can serve as an appropriate model to study cardiac SARS-CoV-2 infection, we measured 151 ACE2 mRNA expression in hPSC-derived CMs. Quantitative RT-PCR revealed that hPSC-152 derived CMs abundantly expressed ACE2 mRNA. We identified numerous host genes that were differentially 226 regulated upon SARS-CoV-2 infection in each of the examined cell types and two-dimensional 227 tissues (Fig. 3c) . 236 GO pathway analysis revealed that infected hPSC-derived CMs and two-dimensional co-237 culture tissues showed upregulation of genes associated with immune cell activation, stress-238 induced transcription, and responses to pathogens including viruses. Consistent with the 343 possibility that disrupted sarcomere gene expression might contribute to reduced EHT 344 contractility, immunostaining of hPSC-derived CMs infected with SARS-CoV-2 revealed evidence 345 of sarcomere loss 3 days following infection (Fig. 6c) , a time point that preceded cell death. cache = ./cache/cord-270550-if748w2n.txt txt = ./txt/cord-270550-if748w2n.txt === reduce.pl bib === id = cord-270698-9w3ap3gz author = Guo, Hua title = Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes date = 2020-05-13 pages = extension = .txt mime = text/plain words = 2496 sentences = 142 flesch = 59 summary = title: Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. Consistent results were observed by binding affinity assays between SARSand SARSr-CoV spike proteins and receptor molecules from bats and humans. In a host-virus arms race situation, the genes involved tend to display dN/dS ratios Codon-based analysis of molecular evolution 536 Bat ACE2 and SARSr-CoV spike sequences were analyzed for positive selection. Identification of key amino acid 671 residues required for horseshoe bat angiotensin-I converting enzyme 2 to function as a 672 receptor for severe acute respiratory syndrome coronavirus cache = ./cache/cord-270698-9w3ap3gz.txt txt = ./txt/cord-270698-9w3ap3gz.txt === reduce.pl bib === id = cord-271693-7tg21up3 author = Zheng, Fan title = Identifying persistent structures in multiscale ‘omics data date = 2020-10-03 pages = extension = .txt mime = text/plain words = 4889 sentences = 291 flesch = 48 summary = Many different approaches have been devised or applied to detect structures in biological data, including standard clustering, network community detection, and low-dimensional data projection [5] [6] [7] , some of which can be tuned for sensitivity to objects of a certain size or scale (so-called 'resolution parameters') [8, 9] . We first explored the idea of measuring community persistence via analysis of synthetic datasets [15] in which communities were simulated and embedded in the similarity network at two different scales (Supplementary Fig. 1a; Methods) . Application to protein-protein interaction networks from budding yeast and human found that HiDeF captured knowledge in GO more significantly than previous pipelines proposed for this task, including the NeXO approach to hierarchical community detection [23] and standard hierarchical clustering of pairwise protein distances calculated by three recent network embedding approaches [24] [25] [26] (Fig. 3a, Fig. 7) . cache = ./cache/cord-271693-7tg21up3.txt txt = ./txt/cord-271693-7tg21up3.txt === reduce.pl bib === id = cord-267831-uu883ofc author = Kang, Yuan-Lin title = Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2 date = 2020-06-15 pages = extension = .txt mime = text/plain words = 1257 sentences = 80 flesch = 44 summary = We describe here potent inhibitory effects on content release and infection by chimeric VSV containing the envelope proteins of Zaire ebolavirus (VSV-ZEBOV) or SARS-CoV-2 (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small molecule inhibitors of the main endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase, PIKfyve. 143 All of these viruses require low pH to trigger viral membrane fusion with the endosomal 144 membranes, and as expected, infection was fully blocked by Bafilomycin A1, which 145 inhibits the vacuolar type H + -ATPase (V-ATPase) acidification activity (Fig. 1C) . Mammalian cell morphology and 671 endocytic membrane homeostasis require enzymatically active phosphoinositide 672 5-kinase PIKfyve The phosphatidylinositol-3-phosphate 5-kinase inhibitor 710 apilimod blocks filoviral entry and infection A transmembrane serine protease is linked to the severe 735 acute respiratory syndrome coronavirus receptor and activates virus entry Characterization of severe acute respiratory syndrome-744 associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry cache = ./cache/cord-267831-uu883ofc.txt txt = ./txt/cord-267831-uu883ofc.txt === reduce.pl bib === id = cord-264051-ps0x2es1 author = Li, Wei title = Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network date = 2020-11-05 pages = extension = .txt mime = text/plain words = 8939 sentences = 450 flesch = 51 summary = Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Besides, these virus fragments containing HIS can increase the H3K27 acetylation (H3K27ac) enrichment at their corresponding regions of the human genome in different mammalian cells and activate the expression of adjacent and distant genes associated with inflammation. Collectively, we identified HIS in SARS-CoV-2 genome, and the targeted human genome loci enriched with cytokines genes suggested that HIS may underly the clinical characteristics of COVID-19 patients and serve as a vital player in the pathological progression. cache = ./cache/cord-264051-ps0x2es1.txt txt = ./txt/cord-264051-ps0x2es1.txt === reduce.pl bib === id = cord-271978-j5enftje author = Zoltán, Köntös title = In Vitro Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) date = 2020-11-10 pages = extension = .txt mime = text/plain words = 2910 sentences = 153 flesch = 52 summary = Conclusion Substantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARS-CoV-2 in vitro, demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasally to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients. Enthused by promising findings from a recent study by Pelletier and colleagues (12) , the present study was interested in Essential Iodine Drops (EID) for oral/nasal decontaminant in known or suspected cases of COVID-19 as a potentially better alternative to PVP-I. Briefly, the three dilutions of Essential Iodine Drops (EID) containing SARS-CoV-2 virus solution (1:1; 2:1 and 3:1) were tested in triplicates for virucidal activity as described by Pelletier and colleagues (12) . In vitro virucidal assay in the present study has indeed demonstrated that 75% and 50% of Essential Iodine Drops (EID) solution reduced SARS-CoV-2 virus titre after 60 seconds and 90 seconds of incubation by an LRV of 2.0 (99%). cache = ./cache/cord-271978-j5enftje.txt txt = ./txt/cord-271978-j5enftje.txt === reduce.pl bib === id = cord-268034-7id7sfsu author = Auerswald, Heidi title = Assessment of Inactivation Procedures for SARS-CoV-2 date = 2020-05-28 pages = extension = .txt mime = text/plain words = 1620 sentences = 100 flesch = 47 summary = This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. The buffers used in this lysis step yield varying results [11, 13, 15, 16] ; however, unlike 224 previous studies [11] , this study found that AVL buffer alone was successfully able to fully 225 inactivate up to 5 log10 of virus from three different primary isolates of SARS-CoV-2. Previous 234 studies have shown that GITC-lysis buffers are able to inactivate SARS-CoV-2 samples [11, 12] ; 235 however, the addition of Triton-X may be necessary for complete inactivation [11] . Therefore, formaldehyde treatment does not appear to be a 247 solution for increased molecular SARS-CoV-2 testing; however, it does remain a viable alternative 248 for sample inactivation or disinfection. cache = ./cache/cord-268034-7id7sfsu.txt txt = ./txt/cord-268034-7id7sfsu.txt === reduce.pl bib === id = cord-270919-0hldozml author = Cortey, Martí title = SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins date = 2020-05-17 pages = extension = .txt mime = text/plain words = 1063 sentences = 73 flesch = 56 summary = title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic offers a unique opportunity to study the introduction and evolution of a pathogen into a completely naïve human population. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%. 54 The aim of the present study was to determine the amino acid substitutions in viral 55 proteins that were widely present in available sequences of SARS-CoV-2, relating them 56 to the known chronology of the pandemic. cache = ./cache/cord-270919-0hldozml.txt txt = ./txt/cord-270919-0hldozml.txt === reduce.pl bib === id = cord-270329-t60t639i author = Schloer, Sebastian title = Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro date = 2020-10-16 pages = extension = .txt mime = text/plain words = 1053 sentences = 77 flesch = 52 summary = title: Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro We tested the antiviral potential of repurposing the antifungal itraconazole and the antidepressant fluoxetine on the production of infectious SARS-CoV-2 particles in the polarized Calu-3 cell culture model and evaluated the added benefit of a combinatory use of these host-directed drugs with remdesivir, an inhibitor of viral RNA polymerase. Importantly, both itraconazole-remdesivir and fluoxetine-remdesivir combinations inhibited the production of infectious SARS-CoV-2 particles > 90% and displayed synergistic effects in commonly used reference models for drug interaction. While drugs 87 directly acting on virus structures are much more likely to completely eliminate the 88 pathogens in shorter treatment time, emerging viral resistance to these antivirals is a major 89 concern, as observed with the influenza neuraminidase inhibitor oseltamivir (Kim et al., itraconazole antiviral activity in SARS-CoV-2 infected Vero cells (Fig. 1b) . cache = ./cache/cord-270329-t60t639i.txt txt = ./txt/cord-270329-t60t639i.txt === reduce.pl bib === id = cord-261877-4y37676n author = Xu, Cong title = Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM date = 2020-06-30 pages = extension = .txt mime = text/plain words = 8754 sentences = 505 flesch = 60 summary = Recent cryoelectron microscopy (cryo-EM) studies on the stabilized ectodomain of SARS-CoV-2 S protein revealed a closed state of S trimer with three RBD domains in "down" conformation (Walls et al., 2020) , as well as an open state with one RBD in the "up" conformation, corresponding to the receptor-accessible state (Walls et al., 2020; Wrapp et al., 2020) . To gain a thorough picture on how the receptor ACE2 binding induces conformational dynamics of the SARS-CoV-2 S trimer and triggers transition towards the postfusion state, we determine the cryo-EM structure of SARS-CoV-2 S trimer in complex with human ACE2 PD domain to 3.8 Å resolution (termed SARS-CoV-2 S-ACE2, Figs. Based on the data, we put forward a mechanism of ACE2 binding-induced conformational transitions of SARS-CoV-2 S trimer from the tightly closed ground prefusion state transforming towards the postfusion state (Fig. 6) . Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding cache = ./cache/cord-261877-4y37676n.txt txt = ./txt/cord-261877-4y37676n.txt === reduce.pl bib === id = cord-273416-332stbjl author = Liu, Tianyuan title = Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease date = 2020-10-01 pages = extension = .txt mime = text/plain words = 2739 sentences = 124 flesch = 46 summary = We created DeCovid, an R shiny app that combines gene expression data of different human tissue from the Genotype-Tissue Expression (GTEx) project and the COVID-19 Disease Map gene collection to explore basal gene expression differences across healthy demographic groups. In this paper, we present the DeCovid app, a Shiny app, to explore basal expression level differences in COVID-19 disease map genes between men and women and different age groups. The DeCovid shiny app combines a selection of human tissue specific GTEx data with the COVID-19 Disease Map database to allow quick exploration of basal gene expression values and differences in the healthy human population for genes described to be important for COVID-19. Here we present the DeCovid app as a resource to explore sex and age differential expression patterns in the healthy population for genes described to be involved in COVID-19 disease pathways. cache = ./cache/cord-273416-332stbjl.txt txt = ./txt/cord-273416-332stbjl.txt === reduce.pl bib === id = cord-273882-tqdcb3oo author = Pratibha, title = Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses date = 2020-08-21 pages = extension = .txt mime = text/plain words = 1958 sentences = 122 flesch = 62 summary = title: Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses We report here a novel method of species characterization based upon the order of these R-group classified amino acids in the linear sequence of the side chains associated with the codon triplets. These ubiquitous forbidden orders (UFO) are unique structures of the viruses that may provide an insight into viruses' chemical behavior and the folding patterns of the proteins. Next, we analyzed protein sequences of 26 viruses (Figures 2, 3 , and Supplementary Figures 1 -4) to search for a ubiquitous forbidden order in each one of them. Among the 26 viruses studied, we noted that the forbidden order BPAB is unique to SARS CoV-2, Rubella, and Avian IB (Figure 3) . We found that at R-group classified sequences of N, B, A, and P in these two samples are identical up to level 4 of the amino acid ordering in the protein structures (Figures 4a, d, g) . cache = ./cache/cord-273882-tqdcb3oo.txt txt = ./txt/cord-273882-tqdcb3oo.txt === reduce.pl bib === id = cord-271971-rstmd0va author = Matsumura, Yasufumi title = Comparison of 12 molecular detection assays for SARS-CoV-2 date = 2020-06-25 pages = extension = .txt mime = text/plain words = 1203 sentences = 74 flesch = 60 summary = We compared 12 molecular diagnostic assays, including 8 commercial kits using 155 respiratory samples (65 nasopharyngeal swabs, 45 oropharyngeal swabs, and 45 sputum) collected at 2 Japanese hospitals. Real-time RT-PCRs 54 were performed using N1, N2, and RNaseP (RP) internal control assays developed by the (4) (with/without EAV), N and E assays developed by Charité in Germany (1) (Corman) 59 with TaqPath™ 1-Step RT-qPCR Master Mix, CG (Thermo Fisher Scientific). In this study, to 79 ensure the presence of SARS-CoV-2 RNA and to avoid false-positives, a sample was 80 defined as positive when positive test results were obtained for more than one genetic 81 locus and assay and the others were defined as negative. 166 Different from multiplex assays that incorporate internal controls such as Roche, Thermo, 167 or BGI kits, this approach needs extra reagents, time, and space in a reaction plate but 168 can be combined with other in-house assays (NIID N2 or Corman E) without any 169 modification. cache = ./cache/cord-271971-rstmd0va.txt txt = ./txt/cord-271971-rstmd0va.txt === reduce.pl bib === id = cord-270257-5f95gve3 author = Jeon, Sangeun title = Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs date = 2020-03-28 pages = extension = .txt mime = text/plain words = 1145 sentences = 79 flesch = 53 summary = Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19. We screened approximately 3,000 FDA-and IND-approved drug library against SARS-CoV to identify antiviral drug candidates (manuscript in preparation). Among the 48 drugs that were evaluated in our study, 24 drugs showed potential antiviral activities against SARS-CoV-2 with IC 50 values in Second, ciclesonide is another interesting drug candidate for further development although its antiviral potency was much lower (IC 50 = 4.33 µM) than niclosamide. Prior to our evaluation of 48 drugs against SARS-CoV-2 infection, we also tested antiviral activity of several other drugs based on the cytopathic effect of the virus in the presence of each drug ( Figure 2 ). cache = ./cache/cord-270257-5f95gve3.txt txt = ./txt/cord-270257-5f95gve3.txt === reduce.pl bib === id = cord-273645-czh3zfb3 author = Lu, Shuaiyao title = Comparison of SARS-CoV-2 infections among 3 species of non-human primates date = 2020-07-17 pages = extension = .txt mime = text/plain words = 2197 sentences = 171 flesch = 65 summary = In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Here, to establish the COVID-19 model, two families including 3 species of non-human primates, which are widely used for animal models with their own advantages and disadvantages, were experimentally infected with SARS-CoV-2, followed by comparisons of clinical symptoms, hematology, biochemical indexes, immunology and histopathology among 3 species. Given that host factors may be involved in viral pathogenesis, we designed an experiment in the present study to investigate whether host genetics, age and gender affect SARS-CoV-2 infection in non-human primates ( Figure 1 ). To know dynamics of viral replication and virus shedding, samples of nasal swabs, throat swabs, anal swabs, feces, blood and tissues were collected at the indicated time points, and SARS-CoV-2 genomes were quantitated by RT-qPCR. cache = ./cache/cord-273645-czh3zfb3.txt txt = ./txt/cord-273645-czh3zfb3.txt === reduce.pl bib === id = cord-273891-7w334xgt author = Kirchdoerfer, Robert N. title = Receptor binding and proteolysis do not induce large conformational changes in the SARS-CoV spike date = 2018-03-31 pages = extension = .txt mime = text/plain words = 3300 sentences = 170 flesch = 55 summary = The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. Subsequent studies of the highly pathogenic human coronavirus S proteins of SARS-64 CoV 15,22 and MERS-CoV 17,22 showed that these viral S1 RBD do indeed sample an 'up' 65 conformation where the receptor-binding site is accessible. 70 To examine the hypothesized conformational transitions induced by proteolysis and 71 receptor binding, we used single-particle cryo-EM to determine structures of S in uncleaved, 72 S1/S2 cleaved and ACE2-bound states. Three-dimensional classification of the S1 RBD 73 positions and corresponding atomic protein models revealed that neither ACE2-binding nor 74 trypsin cleavage at the S1/S2 boundary induced substantial conformational changes in the CoV may use a distinct mechanism of FP2 membrane insertion. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein 381 reveal a prerequisite conformational state for receptor binding cache = ./cache/cord-273891-7w334xgt.txt txt = ./txt/cord-273891-7w334xgt.txt === reduce.pl bib === id = cord-275173-ely3aen3 author = Pickering, Brad S. title = Susceptibility of domestic swine to experimental infection with SARS-CoV-2 date = 2020-09-10 pages = extension = .txt mime = text/plain words = 1917 sentences = 107 flesch = 52 summary = The work reported here aims to determine whether domestic swine are susceptible to 63 SARS-CoV-2 infection, providing critical information to aid public health risk assessments. The data presented in 66 this study provides evidence live SARS-CoV-2 virus can persist in swine for at least 13 days 67 following experimental inoculation. Two pigs (20-10, 20-11) displayed low 237 levels of viral RNA by RT-qPCR at 3 DPI (Table 2, Detection of SARS-CoV-2 was also attempted from whole blood by RT-qPCR, following 253 the sampling schedule outlined in Table 1 . To identify potential target tissues or gross lesions consistent with SARS-CoV-2 disease, 261 necropsy was performed on two animals starting at 3 DPI and every other day up to day 15; with 262 an additional two pigs necropsied at both 22 and 29 DPI (Table 1) (Table 2) . The results presented in this study define domestic swine as a susceptible species albeit at 293 low levels to SARS-CoV-2 viral infection. cache = ./cache/cord-275173-ely3aen3.txt txt = ./txt/cord-275173-ely3aen3.txt === reduce.pl bib === id = cord-271970-i35pic5o author = Boris, Bonaventure title = A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date = 2020-10-28 pages = extension = .txt mime = text/plain words = 6320 sentences = 343 flesch = 52 summary = Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Deep sequencing analysis of the GeCKO cell populations showed more than 94% coverage for both libraries (≥ 10 reads for 61,598 and 54,609 sgRNA-coding sequences out of GeCKO populations were subjected to type 1 IFN treatment in order to induce the antiviral state and, 24h later, incubated with VSV-G-pseudotyped, HIV-1 based LVs coding for an antibiotic resistance cassette. In order to validate the effect of DDX42 KO on HIV-1 infection in another model cell line, two additional sgRNAs were designed (sgRNA-2 and -3) and used in parallel to the one identified in the GeCKO screen (sgDDX42-1) (Figure 2A ). cache = ./cache/cord-271970-i35pic5o.txt txt = ./txt/cord-271970-i35pic5o.txt === reduce.pl bib === id = cord-275690-83nrzfon author = Stanifer, Megan L. title = Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date = 2020-04-24 pages = extension = .txt mime = text/plain words = 4696 sentences = 256 flesch = 52 summary = title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, and in agreement with the results observed in cells depleted of the type III IFN receptor, this increase in infectivity was also associated with an increase in infectious denovo virus particle production ( Fig. 3G ). All together, these results strongly support a model where the type III IFN mediated signaling controls SARS-CoV-2 infection in human intestinal epithelial cells. All together these results show that human colon organoids can support SARS-CoV-2 infection, replication and spread and that the type III IFN response plays a critical role in controlling virus replication. cache = ./cache/cord-275690-83nrzfon.txt txt = ./txt/cord-275690-83nrzfon.txt === reduce.pl bib === id = cord-272513-umuiovrd author = Bindayna, Khalid Mubarak title = Variant analysis of SARS-CoV-2 genomes in the Middle East date = 2020-10-09 pages = extension = .txt mime = text/plain words = 3033 sentences = 217 flesch = 59 summary = We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19. Methods The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID). Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East. • Our hypothesis is that variants found in SARS-CoV-2 genomes from Middle Eastern samples will indicate delivery from Iran. • The aim is to explore the structure of Middle Eastern genome strains using multiple sequence alignment, tree generation and variant prediction (and others). cache = ./cache/cord-272513-umuiovrd.txt txt = ./txt/cord-272513-umuiovrd.txt === reduce.pl bib === id = cord-275252-4e3cn50u author = Rad SM, Ali Hosseini title = Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date = 2020-05-16 pages = extension = .txt mime = text/plain words = 4368 sentences = 302 flesch = 53 summary = In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. A common primary focus of mutational analysis of emerging viruses is the alteration in amino acid sequence of viral proteins that may provide enhanced or new functions for virus replication, immune avoidance, or spread. However, the potential of these mutations to impact upon RNA structure and miRNA recognition provides a basis for ongoing monitoring of viral evolution at these sites in the SARS-CoV-2 genome. cache = ./cache/cord-275252-4e3cn50u.txt txt = ./txt/cord-275252-4e3cn50u.txt === reduce.pl bib === id = cord-271849-wxmr8eki author = Meysman, Pieter title = Tracking SARS-CoV-2 T cells with epitope-T-cell receptor recognition models date = 2020-09-09 pages = extension = .txt mime = text/plain words = 2924 sentences = 166 flesch = 58 summary = In this paper, we demonstrate the use of machine learning to classify SARS-CoV-2 epitope specific T-cell clonotypes in T-cell receptor (TCR) sequencing data. We apply these models to public TCR data and show how they can be used to study T-cell longitudinal profiles in COVID-19 patients to characterize how the adaptive immune system reacts to the SARS-CoV-2 virus. No other epitopes present in TCRex (including the 49 non-SARS-CoV-2 models) were predicted to have a single TCR target within this data set. Once established, these models can be applied to any TCR repertoire data and thus can be used to study putative SARS-CoV-2 reactive T cells in the currently available COVID-19 data. In addition, using such models on longitudinal data reveals a potential difference in temporal dynamics between T cells predicted to react against epitopes that are unique to SARS-CoV-2 and those that are shared among other coronaviruses. cache = ./cache/cord-271849-wxmr8eki.txt txt = ./txt/cord-271849-wxmr8eki.txt === reduce.pl bib === id = cord-272869-381qupdn author = Mirvakili, Seyed M title = Reverse Pneumatic Artificial Muscles for Application in Low-Cost Artificial Respirators date = 2020-05-21 pages = extension = .txt mime = text/plain words = 6039 sentences = 361 flesch = 58 summary = In this work, we propose a low-cost, portable, yet high-performance design for a volume-controlled mechanical ventilator. With the current design, mechanical ventilation for respiration rate ranging from 10 b/min to 30 b/min with a tidal volume range of 150 mL to 1000 mL and I:E ratio of 1:1 to 1:5 can be performed. The state-of-the-art mechanical ventilators address the need for all range of respiratory failures; however, their time-to-manufacture, design sophistication, cost, and scalability for deployment in mass emergencies such as pandemics, make them not a viable solution in many situations. The user interface lets the operator set parameters, stop/start the device, and monitor the pressure and flow rate on the LCD ( Figure 1C ). As depicted in Figure 7 , when pressure drops below -2 cmH2O, the device starts the ventilation and delivers the set tidal volume. cache = ./cache/cord-272869-381qupdn.txt txt = ./txt/cord-272869-381qupdn.txt === reduce.pl bib === id = cord-274528-mr81o9cu author = Li, Fei title = Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide date = 2020-09-12 pages = extension = .txt mime = text/plain words = 6428 sentences = 416 flesch = 53 summary = Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Notably, in addition to prostate, other essential 40 organs, including lung, kidney and liver, which are permissive for SARS-CoV-2 infection in human, were 41 characterized with Tmprss2-postive epithelial cells ( Fig. 1b and Extended Data Fig. 1c ). Consistently, 25 enzalutamide significantly decreased TMPRSS2 expression and inhibited SARS-CoV-2 infection in human 26 prostate cancer cells (Fig. 2) . cache = ./cache/cord-274528-mr81o9cu.txt txt = ./txt/cord-274528-mr81o9cu.txt === reduce.pl bib === id = cord-274114-fglyfz8p author = Minervina, Anastasia A. title = Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection date = 2020-10-01 pages = extension = .txt mime = text/plain words = 5557 sentences = 297 flesch = 56 summary = In this study we use longitudinal TCRalpha and TCRbeta repertoire sequencing to quantitatively track T cell clones that significantly expand and contract after recovery from a mild COVID-19 infection, and determine their phenotype. We reveal the dynamics and the phenotype of the memory cells formed after infection, identify pre-existing T cell memory clones participating in the response, and describe public TCR sequence motifs of SARS-CoV-2-reactive clones, suggesting a response to immunodominant epitopes. At the time of writing, no data on TCR sequences specific to MHC-II class epitopes exist to map specificities of CD4+ T-cells in a similar way as we did with MIRA-specific TCRs. However, a recently published database of 1414 bulk TCRbeta repertoires from COVID-19 patients allowed us to confirm the SARS-CoV-2 specificity of contracting clones indirectly. Public TCRbeta sequences that can recognize SARS-CoV-2 epitopes are expected to be clonally expanded and thus sampled more frequently in the repertoires of COVID-19 patients than in control donors. cache = ./cache/cord-274114-fglyfz8p.txt txt = ./txt/cord-274114-fglyfz8p.txt === reduce.pl bib === id = cord-272986-ebgusf3o author = Cao, Yipeng title = Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel date = 2020-05-17 pages = extension = .txt mime = text/plain words = 4339 sentences = 267 flesch = 56 summary = title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel. We tried to use potential mean force (PMF) to reveal the permeability of different physiological ions and water molecules in the pores of the E protein pentamer. Figure 3A shows the PMF of ions and water molecules permeating through the SARS-CoV-2 E protein pentamer pore. The free energy calculation of the ions permeating through the SARS-CoV-2 pentameric E protein channel strongly suggests that the pore has selection permeability for monovalent ions. cache = ./cache/cord-272986-ebgusf3o.txt txt = ./txt/cord-272986-ebgusf3o.txt === reduce.pl bib === id = cord-280392-ij5gtesw author = Gultom, Mitra title = Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2 date = 2020-11-10 pages = extension = .txt mime = text/plain words = 2253 sentences = 140 flesch = 50 summary = In this study, we inoculated well-differentiated animal AEC cultures of monkey, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two neotropical bat species with SARS-CoV-2. The AEC 131 cultures from 12 different species (rhesus macaque, cat, ferret, dog, rabbit, pig, cattle, goat, llama, 132 camel, and two neotropical bats) were inoculated with 10.000 TCID50 of either IAV or IDV and incubated 133 at 33°C and 37°C. For IDV we observed 137 antigen-positive cells in all AEC model, except for rhesus macaque and one of the neotropical bat 138 species, indicating that the AEC cultures were all well-differentiated and susceptible to virus infection. In the viral sequences in the 96 hpi samples from virus-infected 156 rhesus macaque and cat AEC cultures, we observed no obvious signs of nucleotide transitions that lead 157 to nonsynonymous mutations compared to the respective inoculums ( Fig. 3) , irrespective of 158 temperature and animal species. cache = ./cache/cord-280392-ij5gtesw.txt txt = ./txt/cord-280392-ij5gtesw.txt === reduce.pl bib === id = cord-274409-4ugdxbmy author = Laskar, Rezwanuzzaman title = Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India date = 2020-10-19 pages = extension = .txt mime = text/plain words = 3300 sentences = 190 flesch = 57 summary = title: Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India Further, constitution of 'Disease' mutations in genomes from asymptomatic people was mere 11% but those from deceased patients was over three folds higher at 38% indicating contribution of these mutations to the pathophysiology of the SARS-CoV-2. With a definitive possibility of India becoming the most affected country by SARS-CoV-2 in near future and the demographic burden involved, its pertinent to be analyze the accumulating variations in the genome accounting for possible changes in protein and their potential to alter the virus in any manner. Herein we extend our study using the same congregation of sequences to analyze the nature and composition of the observed mutations and their impact on proteins of SARS-CoV-2. The distribution of Disease and Neutral variants across the different genes of SARS-CoV-2 has been shown in Table 4 and Supplementary file 5. cache = ./cache/cord-274409-4ugdxbmy.txt txt = ./txt/cord-274409-4ugdxbmy.txt === reduce.pl bib === id = cord-279629-t1xjy12y author = Nazneen Akhand, Mst Rubaiat title = Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date = 2020-04-15 pages = extension = .txt mime = text/plain words = 6717 sentences = 379 flesch = 47 summary = The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Hence, the study was designed to develop a chimeric recombinant vaccine against COVID-19 by targeting four major structural proteins of the pathogen, while revealing the evolutionary history of different species of coronavirus based on whole genome and protein domain-based phylogeny. Apart from the human coronaviruses, we introduced other coronaviruses which choose different species of bats, whale, turkey, rat, mink, ferret, swine, camel, rabbit, cow and others as host (Supplementary TableDomain analysis of spike protein of coronaviruses reveals that they contain mainly one signature domains namely, coronavirus S2 glycoprotein (IPR002552), which is present in all the candidates. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach. cache = ./cache/cord-279629-t1xjy12y.txt txt = ./txt/cord-279629-t1xjy12y.txt === reduce.pl bib === id = cord-272626-bw9lbzvt author = Pizzorno, Andrés title = Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia date = 2020-04-02 pages = extension = .txt mime = text/plain words = 2051 sentences = 116 flesch = 40 summary = Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Developed from biopsies of nasal or bronchial cells differentiated in the air/liquid interphase, these models reproduce with high fidelity most of the main structural, functional and innate immune features of the human respiratory epithelium that play a central role 70 in the early stages of infection and constitute robust surrogates to study airway disease mechanisms and for drug discovery (10) . Comparably, daily treatment with 20 µM remdesivir resulted in 7.3 log10 and 7.9 log10 reductions of intracellular SARS-CoV-2 viral titers at 48 hpi in nasal and bronchial HAE, respectively (Fig. 4D, upper panel) . cache = ./cache/cord-272626-bw9lbzvt.txt txt = ./txt/cord-272626-bw9lbzvt.txt === reduce.pl bib === id = cord-279474-c5y2lygj author = Bozzo, Caterina Prelli title = IFITM proteins promote SARS-CoV-2 infection of human lung cells date = 2020-08-18 pages = extension = .txt mime = text/plain words = 1110 sentences = 90 flesch = 55 summary = Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) restrict numerous viral pathogens and are thought to prevent infection by severe acute respiratory syndrome coronaviruses (SARS-CoVs). In striking contrast, however, endogenous IFITM expression promoted genuine SARS-CoV-2 infection in human lung cells both in the presence and absence of interferon. Taken together, our results show that all three IFITMs prevent SARS-CoV-2 S/ACE2-mediated attachment and membrane fusion in single round pseudotype infection assays. Notably, titration experiments showed that IFITMs do not promote genuine SARS-CoV-2 247 infection in HEK239T cells over a broad range of expression levels ( Figure S4E ). (F) Quantification of the entry of VSV(luc)ΔG*-SARS-CoV-2-S by luciferase activity in HEK293T cells transiently expressing indicated proteins (IFITM mutants) and infected 24 h post-transfection with the VSVpp (MOI 0.025) for 16 h. (G) Quantification of the entry of HIV(Fluc)Δenv*-SARS-CoV-2-S by luciferase activity in HEK293T cells stably expressing indicated proteins (IFITM mutants) and ACE2 cache = ./cache/cord-279474-c5y2lygj.txt txt = ./txt/cord-279474-c5y2lygj.txt === reduce.pl bib === id = cord-278869-7zr1118b author = Ravichandran, Supriya title = Antibody repertoire induced by SARS-CoV-2 spike protein immunogens date = 2020-05-13 pages = extension = .txt mime = text/plain words = 2370 sentences = 142 flesch = 52 summary = To better understand antibody response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). The spike ectodomain (S1+S2) generated antibodies that predominantly bound to S1+S2 108 6 (black bar), followed by the S1 protein (blue bar), and 3-fold lower antibody binding to the RBD 109 and the S2 domain (red and green bars, respectively) (Fig. 1D ). Antibody off-rate constants, which describe the fraction of antigen-antibody complexes 119 that decay per second, were determined directly from the serum sample interaction with SARS-120 CoV-2 spike ectodomain (S1+S2), S1, S2, and RBD using SPR in the dissociation phase only for 121 sensorgrams with Max RU in the range of 20-100 RU (Suppl. cache = ./cache/cord-278869-7zr1118b.txt txt = ./txt/cord-278869-7zr1118b.txt === reduce.pl bib === id = cord-280454-etf32afd author = Moustaqil, Mehdi title = SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts date = 2020-06-05 pages = extension = .txt mime = text/plain words = 10152 sentences = 562 flesch = 56 summary = title: SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts Direct cleavage of IRF3 by NSP3 could explain the blunted TypeI IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of IL-6 and inflammatory response observed in COVID-19 patients. In this report, we show that the viral proteases PLpro and 3CLpro of SARS-CoV2 lead to the in-vitro proteolytic cleavage of three important proteins of the host immune response: IRF3, TAB1 and NLRP12 (Fig. 1B) . The presence of the five human-like cleavage sites for IRF3, TAB1 and NLRP12 in a single species shows that it is possible that the SARS viruses could have gained the new functionality of cleaving these Human Innate Immune Proteins in a single reservoir host, potentially in Myotis Davidii. cache = ./cache/cord-280454-etf32afd.txt txt = ./txt/cord-280454-etf32afd.txt === reduce.pl bib === id = cord-276017-2375ipkk author = Chen, Dongsheng title = Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife date = 2020-06-14 pages = extension = .txt mime = text/plain words = 4132 sentences = 365 flesch = 70 summary = Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Previous studies have proposed that animal tissues show high heterogeneity in terms of cellular composition and gene expression profiles 15 , and ACE2 is only expressed in a small proportion of specific cell populations 16 , making single cell analysis of SARS-CoV-2 target cells an attracting field to investigate. Here, we constructed the single cell atlas for livestock, poultry, pets and wildlife, then screened putative SARS-CoV-2 target cells (indicated by the co-expression patterns of SARS-CoV-2 entry receptor ACE2 and SARS-CoV-2 entry activator TMPRSS2) and systematically evaluated their susceptibility, with the aim to understand the virus transmission routes and provide clues to fight against COVID-19. cache = ./cache/cord-276017-2375ipkk.txt txt = ./txt/cord-276017-2375ipkk.txt === reduce.pl bib === id = cord-273613-cpiveo7j author = Cao, Xia title = Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach date = 2020-09-29 pages = extension = .txt mime = text/plain words = 3505 sentences = 178 flesch = 46 summary = Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Affinity maturation of STI-1499 resulted in identification of STI-2020, an antibody with a 35-fold increased affinity for the SARS-CoV-2 Spike receptor-binding domain (RBD) leading to a greater than 50-fold increase in virus neutralization potency against live WA-1/2020 and 2020001 viruses in vitro. In this study, we detail the initial discovery and profiling of a SARS-CoV-2 nAb isolated from a phage display antibody library derived from the B-cell repertoire of over 600 healthy normal individuals. Candidate nAbs were characterized for binding of Spike S1 subunit and neutralization of related clinical SARS-CoV-2 isolates. cache = ./cache/cord-273613-cpiveo7j.txt txt = ./txt/cord-273613-cpiveo7j.txt === reduce.pl bib === id = cord-280994-w8dtfjel author = Peng, Qi title = Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from COVID-19 virus date = 2020-04-23 pages = extension = .txt mime = text/plain words = 2105 sentences = 135 flesch = 55 summary = Here, we describe the near-atomic resolution structure of its core polymerase complex, consisting of nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases, and suggests the mechanism for activation by cofactors. Biochemical studies revealed reduced activity of the core polymerase complex and lower thermostability of individual subunits of COVID-19 virus as compared to that of SARS-CoV. Simultaneous 193 replacement of the nsp7 and nsp8 cofactors further enhanced the efficiency for RNA synthesis 194 to ~2.2 times of that for the SARS-CoV-2 homologous complex ( Figure 4B ). After 3 rounds of extensive 2D classification, ~924,000 particles 437 were selected for 3D classification with the density map of SARS-CoV nsp12-nsp7-nsp8 438 complex (EMDB-0520) as the reference which was low-pass filtered to 60 Å resolution. One severe acute respiratory syndrome 631 coronavirus protein complex integrates processive RNA polymerase and exonuclease activities cache = ./cache/cord-280994-w8dtfjel.txt txt = ./txt/cord-280994-w8dtfjel.txt === reduce.pl bib === id = cord-277253-vy0mvzeb author = Liu, Hongbo title = Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date = 2020-04-11 pages = extension = .txt mime = text/plain words = 2265 sentences = 154 flesch = 52 summary = title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. Inspired by the previous studies, several covalent inhibitors were experimentally identified to inhibit the 3CL pro activity and viral replication of SARS-CoV-2, and some of the complex crystal structures were solved [14, 15] . baicalensis inhibits SARS-CoV-2 3CL pro activity and the most active ingredient baicalein exhibits an IC50 of 0.39 M. We also identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CL pro activity at microM concentration. baicalensis and tested its inhibitory activity against SARS-CoV-2 3CL pro . baicalensis extract at different concentrations on SARS-CoV-2 3CL pro activity were 6 shown in Figure 1A . cache = ./cache/cord-277253-vy0mvzeb.txt txt = ./txt/cord-277253-vy0mvzeb.txt === reduce.pl bib === id = cord-273083-xrydkiu4 author = Pahmeier, Felix title = A versatile reporter system to monitor virus infected cells and its application to dengue virus and SARS-CoV-2 date = 2020-09-01 pages = extension = .txt mime = text/plain words = 999 sentences = 64 flesch = 49 summary = Here, we describe the generation and characterization of a reporter system to visualize dengue virus and SARS-CoV-2 replication in live cells. The system is based on viral protease activity causing cleavage and nuclear translocation of an engineered fluorescent protein that is expressed in the infected cells. Here we describe a reporter system that takes advantage of virus-encoded proteases that are expressed in infected cells to cleave an ER-anchored fluorescent protein fused to a nuclear localization sequence. Using this system, we demonstrate reliable reporting activity for two major human pathogens from the Flaviviridae and the Coronaviridae families: dengue virus and SARS-CoV-2. In order to generate a reporter system that can specifically indicate virus infection, we 219 designed a construct expressing a GFP fusion protein that could selectively be cleaved 220 by viral proteases. However, since no fluorescent 304 protein coding sequence is incorporated into the construct, expression of the DENV 305 polyprotein cannot be followed by live cell imaging. cache = ./cache/cord-273083-xrydkiu4.txt txt = ./txt/cord-273083-xrydkiu4.txt === reduce.pl bib === id = cord-277487-jgbjxgh1 author = Graham, Simon P. title = Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date = 2020-06-20 pages = extension = .txt mime = text/plain words = 5057 sentences = 242 flesch = 53 summary = Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. cache = ./cache/cord-277487-jgbjxgh1.txt txt = ./txt/cord-277487-jgbjxgh1.txt === reduce.pl bib === id = cord-281699-pxof67pl author = Eskier, Doğa title = Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load date = 2020-08-13 pages = extension = .txt mime = text/plain words = 3089 sentences = 169 flesch = 55 summary = In our previous study, we examined the top 10 most frequent mutations in the SARS-CoV-2 nsp12, and identified that four of them are associated with an increase in mutation density in two genes, the membrane glycoprotein (M) and the envelope glycoprotein (E) (the combination of which is hereafter referred to as MoE, as we previously described), which are not under selective pressure, and mutations in these genes are potential markers of reduced replication fidelity (Eskier et al., 2020) . To identify the trends in SARS-CoV-2 mutation load over time, we calculated the average mutation density per day for all isolates for whole genome, S gene, and MoE regions, capping outliers at the 95th and 5th percentile values to minimize the potential effects of sequencing errors ( Fig. 1) . cache = ./cache/cord-281699-pxof67pl.txt txt = ./txt/cord-281699-pxof67pl.txt === reduce.pl bib === id = cord-281684-m3m4mhye author = Fagre, Anna C. title = A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date = 2020-09-28 pages = extension = .txt mime = text/plain words = 3707 sentences = 212 flesch = 47 summary = title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. However, to date, there has been only a gross histological analysis of the lung pathological changes following infection and the impact of SARS-CoV-2 neutralizing antibody clones on lung immune infiltrates has yet to be fully assessed. Those antibody clones that blocked the interaction of the RBD with ACE2 and bound to native spike protein were then tested for neutralization of SARS-CoV-2 in a cytopathic effect (CPE) assay with Vero E6 cells. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity cache = ./cache/cord-281684-m3m4mhye.txt txt = ./txt/cord-281684-m3m4mhye.txt === reduce.pl bib === id = cord-277648-9kxwkcbl author = Overholt, Kalon J. title = Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution date = 2020-06-19 pages = extension = .txt mime = text/plain words = 10003 sentences = 421 flesch = 39 summary = Bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) studies have identified stark transcriptional differences between bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cell (PBMC) samples in hospitalized COVID-19 patients, indicating that immunological responses may be highly compartment-specific [21, 22] . We used identical methods to separately analyze multi-donor scRNA-seq datasets from bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMCs) in COVID-19 patients classified by severity strata as well as healthy control subjects to investigate severity-specific immune dysregulation in the lung and periphery. When we increased this analysis to include all of the cell types found in the BALF (Figure 3A We next investigated pathway-level changes occurring in PBMCs and found that differential gene expression between ARDS and non-ARDS patients supported the detection of statistically enriched pathways through GSEA. cache = ./cache/cord-277648-9kxwkcbl.txt txt = ./txt/cord-277648-9kxwkcbl.txt === reduce.pl bib === id = cord-282372-nmii30mc author = Youk, Jeonghwan title = Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection date = 2020-07-10 pages = extension = .txt mime = text/plain words = 5124 sentences = 294 flesch = 53 summary = Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Although basic molecular mechanisms in SARS-CoV-2 infection have been identified [5] [6] [7] [8] , most findings have been obtained from experiments using non-physiological cell lines 9 , model animals, such as transgenic mice expressing human angiotensin-converting enzyme 2 (ACE2) 10 , ferrets 11 and golden hamsters 12 , or from observation in clinical cohorts 13 and/or inference from in-silico computational methods [14] [15] [16] . Immunostaining for double-stranded viral RNA (dsRNA) and nucleocapsid protein (NP) of SARS-CoV-2 identified widespread viral infection in hAT2 cells co-expressing pro-SFTPC and ACE2 in hAOs ( Fig. 2a and 2b; Extended Data Fig. 3) . cache = ./cache/cord-282372-nmii30mc.txt txt = ./txt/cord-282372-nmii30mc.txt === reduce.pl bib === id = cord-279576-wt4crton author = Fajardo, Álvaro title = Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples date = 2020-05-13 pages = extension = .txt mime = text/plain words = 4842 sentences = 263 flesch = 54 summary = Several methods based on real time reverse transcription polymerase chain reaction (RT-qPCR) for the detection of SARS-CoV-2 genomic RNA have been developed. The aim of the study was to set up an alternative molecular protocol to detect SARS-CoV-2 from clinical samples, without the need of TaqMan probes or post-PCR steps (i.e. gel electrophoresis), which can be implemented in case of difficulties to get specific reagents or kits because of the current pandemic situation. In order to select an appropriate amount of control vector to use in the comparison between the two real time qPCR methods, we prepared plasmids dilutions (107, 106, 105 and 104 copies/μL) and assayed them following both protocols: the probe-based One Step RT-qPCR developed by the University of Hong Kong Poon et al. The amplification data for the SYBR Green-based qPCR protocol showed that the ORF1b-nsp14 region was correctly amplified for all SARS-CoV-2 positive samples (1 to 7) (Fig. 3) . cache = ./cache/cord-279576-wt4crton.txt txt = ./txt/cord-279576-wt4crton.txt === reduce.pl bib === id = cord-284102-rovyvv45 author = Wagner, Teresa R. title = NeutrobodyPlex - Nanobodies to monitor a SARS-CoV-2 neutralizing immune response date = 2020-09-28 pages = extension = .txt mime = text/plain words = 2910 sentences = 190 flesch = 53 summary = Here we identified 11 unique nanobodies (Nbs) with high binding affinities to the SARS-CoV-2 spike receptor domain (RBD). Considering that Nbs targeting diverse epitopes within the RBD:ACE2 interface are beneficial 201 in both reducing viral infectivity and preventing mutational escape, we next combined the most 202 potent inhibitory and neutralizing candidates derived from Nb-Set1 (NM1226, NM1228) and 203 We incubated our previously generated color-coded beads 232 comprising RBD, S1 domain or homotrimeric spike with serum samples from patients or non-233 infected individuals, in addition to dilution series of the combinations NM1226/ NM1230 or 234 NM1228/ NM1230 and used this to detect patient-derived IgGs bound to the respective 235 antigens. As a result, we modified our previously described multiplex immunoassay 303 (MULTICOV-AB, 20 ) and developed a novel diagnostic test called NeutrobodyPlex to monitor 304 the presence and the emergence of neutralizing antibodies in serum samples of SARS-CoV-2 305 infected individuals. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block 681 interaction with ACE2 cache = ./cache/cord-284102-rovyvv45.txt txt = ./txt/cord-284102-rovyvv45.txt === reduce.pl bib === id = cord-280198-bhjw6xc5 author = Olaleye, Omonike A. title = Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro date = 2020-08-14 pages = extension = .txt mime = text/plain words = 1814 sentences = 112 flesch = 49 summary = title: Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 Spike Protein Interaction In Vitro Here in, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a FDA approved drug and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection induced cytopathic effect in vitro. In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. Therefore, targeting 106 the interaction between human ACE2 receptor and the RBD in S protein of SARS-CoV-2 could 107 serve as a promising approach for the development of effective entry inhibitors for potential 108 prevention and/or treatment of COVID-19. Activity of Clioquinol (CLQ) and Analogues against ACE2 Exopeptidase Activity and 725 ACE2 and SARS-CoV-2 Spike (RBD) Protein Interaction cache = ./cache/cord-280198-bhjw6xc5.txt txt = ./txt/cord-280198-bhjw6xc5.txt === reduce.pl bib === id = cord-280979-0vaarrji author = Gauttier, V. title = Tissue-resident memory CD8 T-cell responses elicited by a single injection of a multi-target COVID-19 vaccine date = 2020-08-14 pages = extension = .txt mime = text/plain words = 4302 sentences = 227 flesch = 40 summary = These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1-biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution. These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution. Altogether, these data showed that optimized peptide vaccination against selected SARS-CoV-2 epitopes elicits robust and broad Th1-biased immunogenicity against several structural (S, M, N) and non-structural proteins in HLA-A2 expressing mice and that several peptides induce viral-specific memory CD8 T cells displaying all characteristics of T lymphocyte sentinels in barrier tissues. Using sequence design through reverse vaccinology selection approach based on previous CoVs knowledge on immunodominant epitopes and computational immunology optimization, we developed a combination of 12 CD8 T cell synthetic peptides originating from 11 SARS-CoV-2 structural and non-structural proteins capable to cover HLA polymorphism with high coverage globally and to induce immunogenicity to different proteins independently of HLA alleles expression. cache = ./cache/cord-280979-0vaarrji.txt txt = ./txt/cord-280979-0vaarrji.txt === reduce.pl bib === id = cord-284354-aoti88v7 author = Lupala, Cecylia S. title = Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 date = 2020-05-04 pages = extension = .txt mime = text/plain words = 968 sentences = 63 flesch = 59 summary = title: Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. Angiotensin-converting 302 enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential 303 therapeutic target Computational simulations reveal the binding dynamics between human 318 ACE2 and the receptor binding domain of SARS-CoV-2 spike protein Computational Design of Peptides to Block Binding of 327 the SARS-CoV-2 Spike Protein to Human ACE2 cache = ./cache/cord-284354-aoti88v7.txt txt = ./txt/cord-284354-aoti88v7.txt === reduce.pl bib === id = cord-280922-w6a5ec06 author = Sen, Sanjana title = Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score date = 2020-10-29 pages = extension = .txt mime = text/plain words = 4134 sentences = 289 flesch = 55 summary = Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. Furthermore, a recent review on antibody-dependent enhancement of SARS-CoV-2 stated, "At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses (7) ." This conclusion inspired our study. The results demonstrate that Abs to a specific epitope from N protein plus disease risk factors strongly correlate with COVID-19 disease severity. The DRFS of patients with αEp9 Abs strongly correlates with COVID-19 disease severity (Pearson's r = 0.72, p-value <0.0001, and R 2 = 0.52) (Fig. 4A) . cache = ./cache/cord-280922-w6a5ec06.txt txt = ./txt/cord-280922-w6a5ec06.txt === reduce.pl bib === id = cord-282795-kje7rn57 author = Zheng, Yue title = Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions date = 2020-09-21 pages = extension = .txt mime = text/plain words = 487 sentences = 36 flesch = 58 summary = To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. Pseudotyped MLV viruses were tested on HEK293FT, HEK293T-ACE2, Huh7 and SupT1 cells. To test for specificity of neutralization, we asked whether neutralizing antibodies from SARSCoV-2 patients would exhibit cross-reactivity against a pseudotype expressing SARS-CoV-1 ( Figure 112 4). Characterization of 162 spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with 163 SARS-CoV Veesler D: Structure, Function, and 165 Antigenicity of the SARS-CoV-2 Spike Glycoprotein The 167 D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases 168 infectivity High-efficiency gene 170 transfer into CD34+ cells with a human immunodeficiency virus type 1-based retroviral 171 vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G Pseudotyping Viral Vectors With Emerging Virus Envelope 177 Proteins cache = ./cache/cord-282795-kje7rn57.txt txt = ./txt/cord-282795-kje7rn57.txt === reduce.pl bib === id = cord-280025-4hmecfi0 author = Korber, B title = Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 date = 2020-05-05 pages = extension = .txt mime = text/plain words = 11173 sentences = 524 flesch = 54 summary = We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. Over the past two months, the HIV database team at Los Alamos National Laboratory has turned to developing an analysis pipeline to track in real time the evolution of the SARS-CoV-2 Spike (S) protein in the COVID-19 pandemic, using the Global Initiative for Sharing All Influenza Data GISAID SARS-CoV-2 sequence database as our baseline (Sup. Item 1 is the GISAID acknowledgments table, listing all the groups who contribute sequences to this global effort) (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) . GISAID is the primary SARS-CoV-2 sequence database resource, and our intent is to complement what they provide with visualizations and summary data specifically intended to support the immunology and vaccine communities, and to alert the broader community to changes in frequency of mutations that might signal positive selection and a change in either viral phenotype or antigenicity. cache = ./cache/cord-280025-4hmecfi0.txt txt = ./txt/cord-280025-4hmecfi0.txt === reduce.pl bib === id = cord-281717-kzd9vvci author = Digard, Paul title = Intra-genome variability in the dinucleotide composition of SARS-CoV-2 date = 2020-05-08 pages = extension = .txt mime = text/plain words = 4473 sentences = 266 flesch = 53 summary = CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. CpG suppression amongst coronaviruses does not significantly differ according to genera of virus, but does vary according to host species and primary replication site (a proxy for tissue tropism), supporting the hypothesis that viral CpG content may influence cross-species transmission. 79 SARS-CoV-2 was recently reported to have a CpG composition lower than other members of the 80 betacoronavirus genus, comparable to certain canine alphacoronaviruses; an observation used to draw 81 inferences over its origin and/or epizootic potential (Xia 2020 in GC content (from ~ 0.32 -0.47) was seen across the Coronaviridae, and as expected, all viruses 97 exhibited some degree of CpG suppression, with CpG O:E ratios ranging from 0.37 to 0.74 (Fig 2A) . cache = ./cache/cord-281717-kzd9vvci.txt txt = ./txt/cord-281717-kzd9vvci.txt === reduce.pl bib === id = cord-282604-xp71rkxc author = Nikolaev, EN title = Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date = 2020-05-25 pages = extension = .txt mime = text/plain words = 2181 sentences = 114 flesch = 53 summary = title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. We have performed a pilot study on nasopharynx epithelial swabs already collected from patients with CODIV-19 for RT-qPCR and showed confident identification of the N protein of the SARS CoV-2 virus by mass-spectrometry with the use of a very basic sample preparation procedure. Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients cache = ./cache/cord-282604-xp71rkxc.txt txt = ./txt/cord-282604-xp71rkxc.txt === reduce.pl bib === id = cord-284045-scd3f8vk author = Pape, Constantin title = Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera date = 2020-10-07 pages = extension = .txt mime = text/plain words = 5627 sentences = 300 flesch = 53 summary = Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in specific, sensitive and unbiased assay which complements the portfolio of SARS-CoV-2 serological assays. The dsRNA co-localizing pattern 213 observed for sera from the negative control cohort is by definition non-specific for SARS-CoV-2, 214 but would be classified as a positive hit based on staining intensity alone. The high information content of the IF data (differential staining patterns) 363 together with a machine learning-based approach [45] and the implementation of stable cell lines 364 expressing selected viral antigens in the IF assay will provide additional parameters for 365 classification of patient sera and further improve sensitivity and specificity of the presented IF 366 assay. cache = ./cache/cord-284045-scd3f8vk.txt txt = ./txt/cord-284045-scd3f8vk.txt === reduce.pl bib === id = cord-282878-8qgsq2km author = Fignani, Daniela title = SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature date = 2020-10-23 pages = extension = .txt mime = text/plain words = 7565 sentences = 359 flesch = 43 summary = Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increases ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets. To address this question, we screened the ACE2 expression pattern in human pancreata obtained from adult non-diabetic multiorgan donors and in the insulin-producing human β-cell line EndoC-βH1, using different methodologies, multiple reagents, and publicly available or in-house generated RNA sequencing datasets. Here, we adopted multiple technologies and reagents to thoroughly analyse presence of ACE2, both at mRNA and protein level, in order to evaluate its expression and localization in pancreatic tissue samples obtained from adult non-diabetic multiorgan donors from the INNODIA EUnPOD biobank collection, in enzymatic-and LCM-isolated primary adult human pancreatic islets and in human β-cell line EndoC-βH1. Importantly, a recent report showed that human pancreatic islets can be infected in vitro by SARS-CoV-2 (23), supporting our observations of a specific tropism of the virus due to ACE2 expression. cache = ./cache/cord-282878-8qgsq2km.txt txt = ./txt/cord-282878-8qgsq2km.txt === reduce.pl bib === id = cord-281141-ouno4jpl author = Mahajan, Swapnil title = Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals date = 2020-11-05 pages = extension = .txt mime = text/plain words = 6208 sentences = 307 flesch = 52 summary = A selected pool of 11 predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. We performed T-cell activation assay using the selected 11 epitopes from the SARS-CoV-2 spike antigen in unexposed donors. As shown in Figure Multiple studies have reported pre-existing T-cell immunity in unexposed donors using spike peptide pools and attributed the response to T-cells recognizing epitopes from common coldcausing coronaviruses to which a large section of the global population is exposed (7, 8, 10) . A recent large-scale study mapped a few immunogenic regions in the SARS-CoV-2 proteome responsible for expanding many unique TCRs in a large number of convalescent COVID-19 patients and unexposed healthy donors (21) . cache = ./cache/cord-281141-ouno4jpl.txt txt = ./txt/cord-281141-ouno4jpl.txt === reduce.pl bib === id = cord-285159-gytebbua author = Eydoux, Cecilia title = A Fluorescence-based High Throughput-Screening assay for the SARS-CoV RNA synthesis complex date = 2020-07-07 pages = extension = .txt mime = text/plain words = 3603 sentences = 215 flesch = 59 summary = Here, we report the use of a purified and highly active SARS-CoV replication/transcription complex (RTC) to set-up a high-throughput screening of Coronavirus RNA synthesis inhibitors. Principle of SARS-CoV RNA synthesis detection by a fluorescence-based high throughput screening assay Highlights A new SARS-CoV non radioactive RNA polymerase assay is described The robotized assay is suitable to identify RdRp inhibitors based on HTS -A new SARS-CoV non radioactive RNA polymerase assay is described -The robotized assay is suitable to identify RdRp inhibitors based on HTS the RdRp core nsp12 and shown to confer full activity and processivity to nsp12 (Subissi et al., 2014) . Picogreen kinetic assay was based on polymerase activity of SARS nsp12 in complex with nsp7L8, which catalyzed the reaction using a poly (A) template and uridine triphosphate (UTP). cache = ./cache/cord-285159-gytebbua.txt txt = ./txt/cord-285159-gytebbua.txt === reduce.pl bib === id = cord-283109-ka3n9pft author = Arumugam, Arunkumar title = The Potential Use of Unprocessed Sample for RT-qPCR Detection of COVID-19 without an RNA Extraction Step date = 2020-04-08 pages = extension = .txt mime = text/plain words = 1725 sentences = 103 flesch = 58 summary = Using flu and RSV clinical specimens, we have collected evidence that the RT-qPCR assay can be performed directly on patient sample material from a nasal swab immersed in virus transport medium (VTM) without an RNA extraction step. Using Inf and RSV clinical specimens, we successfully performed RT-qPCR reactions by simply adding a few microliters of the unprocessed sample in viral transport medium (VTM) directly into the RT-qPCR assay master mix. We next tested whether the RNA from SARS-CoV-2 can be detected by directly spiking samples of the non-replicative recombinant virus particles (SeraCare AccuPlex SARS-CoV-2 reference material) in VTM to master mix without an extraction step. As shown in Fig. 3 , the SARS-CoV-2 RNA from directly spiked samples was successfully detected by the RT-qPCR reaction without a nucleic acid extraction step (N1 target shown). cache = ./cache/cord-283109-ka3n9pft.txt txt = ./txt/cord-283109-ka3n9pft.txt === reduce.pl bib === id = cord-284627-qvz63m93 author = Banerjee, Shuvam title = Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence date = 2020-04-09 pages = extension = .txt mime = text/plain words = 3691 sentences = 336 flesch = 67 summary = The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. Interpretation The fatality outcome depends on three important factors (a) number of mutation (b) rarity of the allelic variation and (c) functional consequence of the mutation at protein level. 12, 14 In this study, we comprehensively analyzed the whole genome sequence homology from the available patient data uploaded by affected countries in NCBI Virus database, identified the mutations developed by different strains from the ancestor strain and studied the impact of those mutations at functional level. In summary, the present study reveals that the fatality rate increases with not only the number of mutations but also depending on its allelic rarity as well as functional alteration of protein. cache = ./cache/cord-284627-qvz63m93.txt txt = ./txt/cord-284627-qvz63m93.txt === reduce.pl bib === id = cord-284068-sbon3aes author = Mok, Chee Keng title = Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date = 2020-06-22 pages = extension = .txt mime = text/plain words = 1798 sentences = 104 flesch = 49 summary = Validation assays to determine changes in infectious virus titres upon treatment was carried out by testing selected hit compounds in dose-dependent assays in Vero E6 to confirm the primary screen observation and also in the human hepatocarcinoma HuH7 cell line as the latter cell line expresses high levels of the ACE2 receptor (10) and supports replication of coronaviruses (11) . While recent data has shown that vitamin D levels are negatively associated with morbidity and mortality of COVID-19 cases (13, 14) , this is the first report of a direct inhibitory effect of calcitriol on SARS-CoV-2. The authors speculated that vitamin D supplementation could protect against SARS-CoV-2 infection and improve patient disease outcomes (16) , and our finding certainly provides credence to this hypothesis. Given the high transmissibility of SARS-CoV-2 globally (23), if these findings can be replicated in clinical trials, calcitriol may certainly prove to be an effective tool in the effort to control the pandemic while waiting for an effective vaccine to be rolled out globally. cache = ./cache/cord-284068-sbon3aes.txt txt = ./txt/cord-284068-sbon3aes.txt === reduce.pl bib === id = cord-286001-pu1fetq7 author = Zang, Ruochen title = TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes date = 2020-04-23 pages = extension = .txt mime = text/plain words = 2049 sentences = 145 flesch = 50 summary = In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. Importantly, we found that 160 expression of TMPRSS4 but not ST14 also resulted in a significant increase in the levels of viral RNA and infectious virus titers in the presence of ACE2 ( Fig. 3B and S3C) . Collectively, we have shown that TMPRSS2 and TMPRSS4 activate SARS-CoV-2 S and 187 enhance membrane fusion and viral endocytosis into host cells. Importantly, abrogating TMPRSS4 expression led 209 to a 4-fold reduction in SARS-CoV-2 chimera virus replication in human enteroid, even 210 more significant than TMPRSS2 knockout (Fig. 4B) , highlighting its importance in 211 mediating virus replication in primary cells. It is possible that in the 293 small intestine, whereas SARS-CoV-2 is relatively stable, additional proteases such as 294 trypsin likely enhance viral pathogenesis by triggering more robust IEC fusion (Fig. S2A) . cache = ./cache/cord-286001-pu1fetq7.txt txt = ./txt/cord-286001-pu1fetq7.txt === reduce.pl bib === id = cord-284191-05djnz4p author = Bert, Nina Le title = Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals date = 2020-05-27 pages = extension = .txt mime = text/plain words = 1944 sentences = 103 flesch = 53 summary = To study SARS-CoV-2 specific T cells associated with viral clearance, we collected peripheral blood of 24 individuals who recovered from mild to severe COVID-19 (demographic, clinical and virological information are summarized in Extended Data Table 1 ) and studied the T cell response against selected structural (nucleocapsid protein-NP) and non-structural proteins (NSP7 and NSP13 of ORF1) of the large SARS-CoV-2 proteome ( Figure 1A) . To confirm and further delineate the multispecificity of the NP-specific T cell response detected ex vivo in COVID-19 recovered patients, we defined in nine individuals, the distinctive sections of NP targeted by T cells. This is consistent with the findings of Grifoni et al 11 : using selected peptides, they detected ORF-1 specific T preferentially in some SARS-CoV-2 unexposed donors while T cells of COVID-19 recovered donors preferentially recognized structural proteins. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals cache = ./cache/cord-284191-05djnz4p.txt txt = ./txt/cord-284191-05djnz4p.txt === reduce.pl bib === id = cord-286810-kq2gu5cc author = Klein, Joshua A. title = Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft date = 2020-05-31 pages = extension = .txt mime = text/plain words = 2581 sentences = 145 flesch = 50 summary = We summarize the principles for glycopeptide data analysis and show use of our GlycReSoft tool to analyze SARS-CoV-2 spike protein site-specific glycosylation. A glycoproteomics database search engine includes functions for (i) search space construction, (ii) mass spectrum pre-processing, (iii) a scoring model that evaluates Glycopeptide LC-MS algorithms p. The search space uses an input protein list to calculate proteolytic peptides with a list of constant and variable modification rules that include glycosylation. The use of a long LC gradient combined with a single HCD collision energy value of 50% maximized the number of glycopeptides that were While the glycopeptide tandem mass spectrum shown in Figure 3 was acquired using stepped collision energy, the S protein tandem MS data were acquired using HCD set at 50%. We show an example of the use of GlycReSoft to assign SARS-CoV-2 S protein glycosylation from a published data set in which we identify sulfated N-glycans not identified in the original manuscript. cache = ./cache/cord-286810-kq2gu5cc.txt txt = ./txt/cord-286810-kq2gu5cc.txt === reduce.pl bib === id = cord-286466-scokdxp2 author = Tani, Hideki title = Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein date = 2020-08-23 pages = extension = .txt mime = text/plain words = 2558 sentences = 155 flesch = 54 summary = The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an immunofluorescence assay (IFA). The neutralization values of the serum 31 samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative 32 donors against the pseudotyped virus infection evaluated by the CRNT were compared with 33 was designated as pCAG-SARS-CoV-2. Vero cells were treated with serially diluted sera or whole blood of convalescent patients with 145 COVID-19 or PCR-negative donors and then inoculated with Sfullpv, St19pv, or VSVpv. To 146 remove hematopoietic cells from whole blood samples, centrifugation was performed at 2,000 × g 147 for 5 min. To determine the specificity of infection of Sfullpv and St19pv, a neutralization assay of the 183 pseudotyped viruses was performed using sera of two hospitalized COVID-19 patients. cache = ./cache/cord-286466-scokdxp2.txt txt = ./txt/cord-286466-scokdxp2.txt === reduce.pl bib === id = cord-285592-0in22wzv author = Lemoine, Frédéric title = COVID-Align: Accurate online alignment of hCoV-19 genomes using a profile HMM date = 2020-05-25 pages = extension = .txt mime = text/plain words = 3755 sentences = 262 flesch = 64 summary = Moreover, COVID-Align provides summary statistics, which can be used to determine the sequencing quality and evolutionary novelty of input genomes (e.g. number of new mutations and indels). Unique mutations and indels are possibly due to errors (sequencing, assembly etc.), while new ones (seen at least twice in submitted genomes, for the first time) likely correspond to evolutionary novelties (see Sup. Info. Right: Statistics summary, displaying the number of High and Low Quality genomes, and the number of evolutionary events (mutations, gaps, gap openings, insertions, insertion openings). For each of the input genomes, COVID-Align computes a series of summary statistics to help users analyze their data, remove problematic sequences, and detect those containing evolutionary novelties. When new sequences with confirmed insertions and deletions will be available from emerging genomes, they will be incorporated in the profile and the resulting MSA will closely account for these indels. cache = ./cache/cord-285592-0in22wzv.txt txt = ./txt/cord-285592-0in22wzv.txt === reduce.pl bib === id = cord-291012-y0ufzx93 author = Ye, Qing title = SARS-CoV-2 infection causes transient olfactory dysfunction in mice date = 2020-11-10 pages = extension = .txt mime = text/plain words = 1846 sentences = 125 flesch = 51 summary = Robust viral nucleocapsid (N) protein was detected in the 89 lung from SARS-CoV-2 infected hACE2 mice, but not from the control animals 90 ( Figure S1B ). Remarkably, a significantly increased latency (152.8 s v.s. 81.8 s; p=0.022) to locate 103 food pellets was observed in SARS-CoV-2 infected mice as compared with the control 104 animals on 2 dpi ( Figure 1D ). Further RT-qPCR assay showed a dozen of 211 OR genes were significantly down regulated in response to SARS-CoV-2 infection 212 ( Figure 5E ), which may also attribute to the observed olfactory dysfunction. Interestingly, SARS-CoV-2 positive signals were also observed in mOSNs and HBCs 245 of infected animals, although we didn't detect any hACE2 expression in these cells. A) Representative multiplex immunofluorescent staining shows SARS-CoV-2 674 (SARS-CoV-2 N protein-positive) infects sustentacular cells (CK8-positive, yellow 675 arrows), Bowman's gland cells (Sox9/CK8-positive, white arrows), microvillar cells 676 (CD73/CK8-positive, cyan arrows), HBCs (CK5-postitive, gold arrows) and iOSNs 677 (GAP43-positive cache = ./cache/cord-291012-y0ufzx93.txt txt = ./txt/cord-291012-y0ufzx93.txt === reduce.pl bib === id = cord-287172-h8zoplkm author = Ghobrial, Moheb title = The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors date = 2020-10-21 pages = extension = .txt mime = text/plain words = 7020 sentences = 315 flesch = 55 summary = To understand the potential mechanisms underlying SARS-CoV-2 tropism for brain vasculature, we constructed a molecular atlas of the expression patterns of SARS-CoV-2 viral entry-associated genes (receptors and proteases) and SARS-CoV-2 interaction partners in human (and mouse) adult and fetal brain as well as in multiple non-CNS tissues in single-cell RNA-sequencing data across various datasets. Notably, the top regulated pathways included inflammation, angiogenesis, coagulation, cell-extracellular matrix interaction, viral-host interaction, vascular metabolism, blood-brain-barrier permeability, and reactive oxygen species (ROS) in both the adult and the fetal brain endothelium ( Together, these data reveal that CTSB is highly expressed in various endothelial cell clusters of the fetal and adult human brain and that pathways downstream of CTSB might provide a suggestive explanation of some of the neurovascular symptoms observed in COVID-19 cache = ./cache/cord-287172-h8zoplkm.txt txt = ./txt/cord-287172-h8zoplkm.txt === reduce.pl bib === id = cord-281565-v8s2ski3 author = Belmonte-Reche, Efres title = Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date = 2020-08-20 pages = extension = .txt mime = text/plain words = 4545 sentences = 253 flesch = 53 summary = These PQS and PiMS have been assessed according to their potential to form, uniqueness, frequency of appearance, conservation rates between 3297 different 2019-nCoV clinical cases, confirmed quadruplex-forming sequence presence and localization within the genome. Then, these PQS and PiMS were evaluated by their frequency of appearance in the corresponding genome, the presence of known-to-form quadruplex structures sequences within and their probability of quadruplex-formation score (as the mean of G4Hunter (52) and the adaptation of the PQSfinder algorithm (53) ). A flexible configuration of quadruplex definitions will detect larger amounts of candidates at the expense of requiring more computing power and accepting sequences that are more ambiguous in forming quadruplex structures in vitro (as determined by their score; with longer loops, smaller runs, more bulges and more complementary G/C %, Figure 1 , B). Expanding the search for common candidates to the entire virus realm, we matched one PQS and PiMS from the 2019-nCoV with the potential quadruplexes found in four viruses from cache = ./cache/cord-281565-v8s2ski3.txt txt = ./txt/cord-281565-v8s2ski3.txt === reduce.pl bib === id = cord-285088-krim73zt author = Wang, Deguo title = One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay date = 2020-04-21 pages = extension = .txt mime = text/plain words = 1792 sentences = 82 flesch = 57 summary = title: One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay Objective This study was to establish one-pot real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay and one-pot visual RT-LAMP assay for the detection of COVID-19. The analytic sensitivities of the newly developed real-time RT-LAMP assay and visual RT-LAMP assay were determined with pUC57-N DNA ranging from 2-0.02 fg, and the reaction mixtures were heated at the optimal temperature for 60 min in a StepOneTM System (Applied Biosystems, Foster City, CA, USA) or in a water bath, when water bath was used, the reaction tube was sunk into water. The detection limits of the one-pot real-time RT-LAMP assay and the one-pot visual RT-LAMP assay were determined using pUC57-N DNA ranging from 2-0.02 fg at 59 °C for 60 min in a StepOneTM System (Applied Biosystems, Foster City, CA, USA) or in a water bath. cache = ./cache/cord-285088-krim73zt.txt txt = ./txt/cord-285088-krim73zt.txt === reduce.pl bib === id = cord-287658-c2lljdi7 author = Lopez-Rincon, Alejandro title = Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date = 2020-09-10 pages = extension = .txt mime = text/plain words = 4766 sentences = 253 flesch = 55 summary = The discovered sequences are first validated on samples from other repositories, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. The discovered sequences are validated on samples from NCBI and GISAID, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. For example, we can use this sequencing data with cDNA, resulting from the PCR of the original viral RNA; e,g, Real-Time PCR amplicons to identify the SARS-CoV-2 16 . The global impact of SARS-CoV-2 prompted researchers to apply effective alignment-free methods to the classification of the virus: For example, in 26 the authors propose the use of Machine Learning Digital Signal Processing for separating the virus from similar strains, with remarkable accuracy. We calculated the frequency of appearance of different primer sets' sequences used in SARS-CoV-2 RT-PCR tests developed by WHO referral laboratories and compared it to our primer design in the dataset from the GISAID ( Table 2) repository. cache = ./cache/cord-287658-c2lljdi7.txt txt = ./txt/cord-287658-c2lljdi7.txt === reduce.pl bib === id = cord-291710-ixun0c8g author = Su, Haixia title = Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date = 2020-04-14 pages = extension = .txt mime = text/plain words = 2572 sentences = 154 flesch = 53 summary = A crystal structure of SARS-CoV-2 3CLpro in complex with baicalein, the first non-covalent, non-peptidomimetic small-molecule inhibitor, was also determined, revealing a unique binding mode of this natural product with the protease. To validate the binding of baicalin and baicalein with SARS-CoV-2 3CLpro and exclude the suspicion of being the pan-assay interference compounds (PAINS) (15) , their binding affinities with the protease were measured by isothermal titration calorimetry (ITC), widely known as an invaluable tool used to determine thermodynamic parameters of protein-ligand interactions such as Kd (Fig. 1, A and B ; Table 1 ). Moreover, the ITC profiles in combination with their chemical structures suggest that baicalin and baicalein act as noncovalent inhibitors of SARS-CoV-2 3CLpro with a high ligand binding efficiency. The mode of action of baicalein and the structural determinants associated with its binding with SARS-CoV-2 3CLpro were further explored using X-ray protein crystallography. cache = ./cache/cord-291710-ixun0c8g.txt txt = ./txt/cord-291710-ixun0c8g.txt === reduce.pl bib === id = cord-281679-xmbnpawj author = Meekins, David A. title = Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date = 2020-08-16 pages = extension = .txt mime = text/plain words = 3402 sentences = 191 flesch = 46 summary = In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Cats, hamsters, and ferrets are highly susceptible to SARS-CoV-2 infection, demonstrate varying clinical and pathological disease manifestations, readily transmit the virus to naïve animals, and mount a virusspecific immune response [22] [23] [24] [25] [26] [27] [28] . Pigs are therefore unlikely to play an important role in the COVID-19 pandemic as a virus reservoir or as a pre-clinical animal model to study SARS-CoV-2 pathogenesis or develop novel countermeasures. cache = ./cache/cord-281679-xmbnpawj.txt txt = ./txt/cord-281679-xmbnpawj.txt === reduce.pl bib === id = cord-291420-40xsypzt author = Nelson-Sathi, Shijulal title = Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction date = 2020-10-01 pages = extension = .txt mime = text/plain words = 2274 sentences = 145 flesch = 54 summary = title: Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction Formation of a stable binding interface between the Spike (S) protein Receptor Binding Domain (RBD) of SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) of host actuates viral entry. In silico structure modelling of interfaces induced by mutations on residues which directly engage ACE2 or lie in the near vicinity revealed molecular rearrangements and binding energies unique to each RBD mutant. The structural analysis of the mutated spike glycoprotein of SARS-CoV-2 RBD domain was done to assess the impact of interface amino acid residue mutations on binding affinity towards the human ACE2 (hACE2) receptor. Comparative analysis of structures showed key differences in all three binding clusters of SARS-CoV-2 RBD wild type and mutant interfaces with human or mouse ACE2 (Figure 2C, 2D and Table S1 ). cache = ./cache/cord-291420-40xsypzt.txt txt = ./txt/cord-291420-40xsypzt.txt === reduce.pl bib === id = cord-290445-vb53bih9 author = Ahmed, Shiek SSJ title = Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date = 2020-04-23 pages = extension = .txt mime = text/plain words = 3793 sentences = 208 flesch = 42 summary = Secondly, the viral replication machinery network from SET-B with 332 seed proteins extended to 1486 neighboring proteins with 11438 interacting edges which representing the mechanism attributed to evasion of the SARS-CoV2 genome into the host. Similarly, the viral replication machinery network was acquired with 1522 proteins with 9747 interacting edges showing the complex SARS-CoV-2 mechanism in the human lungs. These common molecules represent the inter-connecting mechanism involved in the transcription machinery, immune response, cell growth and/or maintenance, transport, metabolism, protein metabolism, cell communication and signal transduction that activated upon virus binding and has been subsequently utilized for viral replication process (S5 Table) Also mapping with other viral infection dataset, 50 hub proteins of the replication machinery network have noticed in influenza virus infection (S4 Table) , which suggests SARS-CoV2 and influenza may have a similar mode of host infection machinery [17] . The molecular pathways of interconnecting protein hubs could be the intermediate phase that connects the receptor activation mechanism and viral replication process (Fig 10) . cache = ./cache/cord-290445-vb53bih9.txt txt = ./txt/cord-290445-vb53bih9.txt === reduce.pl bib === id = cord-288705-f3zqhpx1 author = Slaine, Patrick title = Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model date = 2020-10-01 pages = extension = .txt mime = text/plain words = 5892 sentences = 325 flesch = 45 summary = title: Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model Selective disruption of IAV glycoprotein processing and accumulation by 6-TG and 6-TGo correlated with unfolded protein response (UPR) activation and HA accumulation could be partially restored by the chemical chaperone 4-phenylbutyrate (4PBA). Thiopurines inhibited replication of the human coronavirus OC43 (HCoV-OC43), which also correlated with UPR/ISR activation and diminished accumulation of ORF1ab and nucleocapsid (N) mRNAs and N protein, which suggests broader disruption of coronavirus gene expression in ER-derived cytoplasmic compartments. Our results suggest that 406 the effects are unlikely to be mediated through DNA or RNA incorporation of 6-TG because 1) 407 replicative stress does not specifically induce UPR; 2) among viral proteins, glycoprotein 408 accumulation and processing was preferentially disrupted; 3) messenger RNA levels of HA and 409 NA were not affected. cache = ./cache/cord-288705-f3zqhpx1.txt txt = ./txt/cord-288705-f3zqhpx1.txt === reduce.pl bib === id = cord-291677-zcbyhsf1 author = Wilamowski, M. title = Methylation of RNA Cap in SARS-CoV-2 captured by serial crystallography date = 2020-08-16 pages = extension = .txt mime = text/plain words = 5348 sentences = 308 flesch = 56 summary = To investigate the 2′-O methyltransferase activity of SARS-CoV-2 Nsp10/16, we applied fixed-target serial synchrotron crystallography (SSX) which allows for physiological temperature data collection from thousands of crystals, significantly reducing the x-ray dose while maintaining a biologically relevant temperature. We conducted serial synchrotron crystallography (SSX) experiments at 297 K to test whether low radiation dose could help uncover the structure of Nsp10/16 in a complex with Cap-1. The SARS-CoV-2 Nsp10/16 2′-O MTase complex provides a molecular arrangement for binding of the mRNA Cap-0 and subsequent methylation of the first transcribed nucleotide. The further development of SSX and implementation of time-resolved SSX crystallography is an approach that could visualize chemical processes and protein molecular dynamics -such as of the transfer of the methyl group catalyzed by Nsp10/16 2′O-MTase from SARS-CoV-2. Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2′-o-methyltransferase nsp10/nsp16 complex cache = ./cache/cord-291677-zcbyhsf1.txt txt = ./txt/cord-291677-zcbyhsf1.txt === reduce.pl bib === id = cord-290694-jmav8xi4 author = Bridgland, Victoria M. E. title = Why the COVID-19 pandemic is a traumatic stressor date = 2020-09-22 pages = extension = .txt mime = text/plain words = 1102 sentences = 68 flesch = 57 summary = The COVID-19 pandemic does not fit into prevailing Post-traumatic Stress Disorder (PTSD) models, or diagnostic criteria, yet emerging research shows traumatic stress symptoms as a result of this ongoing global stressor. Nevertheless, among a sample of online participants (N = 1,040) in five western countries, we found participants had PTSD-like symptoms for events that had not happened and when participants had been directly (e.g., contact with virus) or indirectly exposed to COVID-19 (e.g., via media). Posttraumatic Stress Disorder Checklist-5 (PCL-5 (22)), adapted to measure pre/peri/post-145 traumatic reactions, and measures of general emotional reactions, well-being, psychosocial 146 functioning, and depression, anxiety, and stress symptoms. We then re-presented the 209 same list of events, but asked participants to select events they were concerned about 210 happening in the future ("other" events led to three additional categories [seven responses The PTSD Checklist (PCL-5 (22)). cache = ./cache/cord-290694-jmav8xi4.txt txt = ./txt/cord-290694-jmav8xi4.txt === reduce.pl bib === id = cord-287205-k64svq6n author = Pollet, Jeroen title = SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice date = 2020-11-05 pages = extension = .txt mime = text/plain words = 4245 sentences = 282 flesch = 56 summary = title: SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as a suitable vaccine candidate against COVID-19. The modified SARS-CoV-2 antigen, 264 RBD219-N1C1, when formulated on Alhydrogel ® , was shown to induce virus-neutralizing antibodies 265 in mice, equivalent to those levels elicited by the wild-type (RBD219-WT) recombinant protein 266 counterpart. Here we report on a yeast-expressed SARS-CoV-2 RBD219-N1C1 protein and its potential as a 397 vaccine candidate antigen for preventing COVID-19. In a mouse virus challenge model for the SARS CoV RBD recombinant protein vaccine, we 422 found that Alhydrogel ® formulations induced high levels of protective immunity but did not 423 stimulate eosinophilic immune enhancement, suggesting that Alhydrogel ® may even reduce immune The selection of the P. cache = ./cache/cord-287205-k64svq6n.txt txt = ./txt/cord-287205-k64svq6n.txt === reduce.pl bib === id = cord-293640-pgrrurrc author = Tripathi, Satyendra C title = Renal carcinoma is associated with increased risk of coronavirus infections date = 2020-07-06 pages = extension = .txt mime = text/plain words = 3724 sentences = 202 flesch = 48 summary = We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. TCGA data analysis also showed increased expression of all receptors except TMPRSS2 in renal tumor tissues as compared to their adjacent normal (Sup Fig 1) . Further, we specifically analyzed ACE2, which is a primary SARS-CoV receptor and DPP4, highly correlated to ACE2 across the kidney cancer subtypes along with immune cell signatures (innate and adaptive immunity, inflammatory cytokines and chemokines). ACE2, DPP4, ANPEP, and ENPEP each associated with a high level of immune infiltration, inflammatory chemokines, cytokines and markers of an immunosuppressive microenvironment and T cell exhaustion in KIRC tumors. The Tumor Immune System Interaction database (TISIDB) (http://cis.hku.hk/TISIDB/) platform was used to analyze the correlation of ACE2 with other CoV receptors (DPP4, ANPEP, ENPEP, TMPRSS2) expression in different renal carcinoma subtypes. cache = ./cache/cord-293640-pgrrurrc.txt txt = ./txt/cord-293640-pgrrurrc.txt === reduce.pl bib === id = cord-291590-24psoaer author = Ogando, Natacha S. title = The enzymatic activity of the nsp14 exoribonuclease is critical for replication of Middle East respiratory syndrome-coronavirus date = 2020-06-20 pages = extension = .txt mime = text/plain words = 4299 sentences = 228 flesch = 52 summary = In line with such a role, ExoN-knockout mutants of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) were previously found to have a crippled but viable hypermutation phenotype. Remarkably, using an identical reverse genetics approach, an extensive mutagenesis study revealed the corresponding ExoN-knockout mutants of another betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), to be non-viable. Our study thus reveals an additional function for MERS-CoV nsp14 ExoN, which apparently is critical for primary viral RNA synthesis, thus differentiating it from the proofreading activity thought to boost long-term replication fidelity in MHV and SARS-CoV. Strikingly, we now established that the equivalent knockout mutants of MERS-CoV ExoN are non-viable and completely deficient in RNA synthesis, thus revealing an additional and more critical function of ExoN in coronavirus replication. cache = ./cache/cord-291590-24psoaer.txt txt = ./txt/cord-291590-24psoaer.txt === reduce.pl bib === id = cord-290290-wyx9ib7s author = Sinegubova, Maria V. title = High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date = 2020-11-05 pages = extension = .txt mime = text/plain words = 5978 sentences = 304 flesch = 49 summary = title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. cache = ./cache/cord-290290-wyx9ib7s.txt txt = ./txt/cord-290290-wyx9ib7s.txt === reduce.pl bib === id = cord-291156-zxg3dsm3 author = Bernasconi, Anna title = Empowering Virus Sequences Research through Conceptual Modeling date = 2020-05-01 pages = extension = .txt mime = text/plain words = 4600 sentences = 206 flesch = 38 summary = We hereby present the Viral Conceptual Model (VCM), centered on the virus sequence and described from four perspectives: biological (virus type and hosts/sample), analytical (annotations and variants), organizational (sequencing project) and technical (experimental technology). -We propose a new Viral Conceptual Model (VCM), a general conceptual model for describing viral sequences, organized along specific dimensions that highlight a conceptual schema similar to GCM [6] ; -Focusing on SARS-CoV2, we show how VCM can be profitably linked to a phenotype database with information on COVID-19 infected patients; -We provide a list of interesting queries replicating newly released literature on infectious diseases; these can be easily performed on VCM. Some interesting portals have become interfaces to GISAID data with particular focuses: NextStrain [18] overviews emergent viral outbreaks based on the visualization of sequence data integrated with geographic information, serology, and host species; CoV-GLUE, 9 part of the GLUE suite [38] , contains a database of replacements, insertions and deletions observed in sequences sampled from the pandemic. cache = ./cache/cord-291156-zxg3dsm3.txt txt = ./txt/cord-291156-zxg3dsm3.txt === reduce.pl bib === id = cord-289367-zna8qkkv author = Wirden, Marc title = Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2 date = 2020-06-30 pages = extension = .txt mime = text/plain words = 1193 sentences = 72 flesch = 61 summary = Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct. Conclusions In this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Then, each laboratory selected 45 to 49 samples firstly detected 88 using the Cobas 6800 with a stratification according to the Ct of the E gene Cobas results, 89 allowing to cover the whole linear range of the assays. This 207 is a limitation of our study as we did not assessed comparatively the limit of detection of the 208 two methods but the reliability of their Ct values among COBAS 6800 positive samples, 209 excluding those that could be negative with COBAS 6800 and positive with RealStar in this 210 range of low viral loads. RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high 278 throughput system cache = ./cache/cord-289367-zna8qkkv.txt txt = ./txt/cord-289367-zna8qkkv.txt === reduce.pl bib === id = cord-291523-4dtk1kyh author = Nguyen, Thanh Thi title = Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date = 2020-07-01 pages = extension = .txt mime = text/plain words = 5361 sentences = 313 flesch = 62 summary = Outcomes of a phylogenetic analysis suggest that the virus belongs to the genus Betacoronavirus, sub-genus Sarbecovirus, which includes many bat SARS-like CoVs and SARS CoVs. Another study in [5] confirms this finding by analysing genomes obtained from three adult patients admitted to a hospital in Wuhan on December 27, 2019. With the cut-off parameter C is set equal to 0.7, the hierarchical clustering algorithm separates the reference sequences into 6 clusters in which cluster "5" comprises all examined viruses of the Sarbecovirus sub-genus, including many SARS CoVs, bat SARS-like CoVs and pangolin CoVs (Fig. 7A) . With the results obtained in Fig. 7D (and also in the experiments with the DBSCAN method presented next), we support a hypothesis that bats or pangolins are the probable origin of SARS-CoV-2. In this Appendix, we first present results of the hierarchical clustering method applied to the dataset that combines Set 1 of reference sequences (Table 1 ) with all 334 SARS-CoV-2 sequences (see Fig. 9 ). cache = ./cache/cord-291523-4dtk1kyh.txt txt = ./txt/cord-291523-4dtk1kyh.txt === reduce.pl bib === id = cord-287372-ya5uvoki author = Böszörményi, Kinga P. title = Comparison of SARS-CoV-2 infection in two non-human primate species: rhesus and cynomolgus macaques date = 2020-11-05 pages = extension = .txt mime = text/plain words = 3973 sentences = 249 flesch = 58 summary = This study provides a detailed description of the pathogenesis of a low-passage SARS-CoV-2 isolate in two macaque models and suggests that both species represent an equally good model in research for both COVID-19 prophylactic and therapeutic treatments. Rhesus macaques have also been applied 116 in COVID-19 pathogenesis studies [22, 24, 32, 33] , and to test the efficacy of remdesivir in the 117 treatment of SARS-CoV-2 infection [34] . we compared SARS-CoV-2 replication in rhesus and cynomolgus macaque species and 129 monitored signs of COVID-19-like disease symptoms for three weeks after infection. The animals from this study were not 342 euthanized to be able to perform re-infection studies or to monitor them for late clinical signs, 343 or co-morbidities related to We conclude that the course of SARS-CoV-2 infection of both macaque species is highly 345 similar, indicating that they are equally suitable models to test vaccines and antivirals in a 346 preclinical setting for safety and efficacy. cache = ./cache/cord-287372-ya5uvoki.txt txt = ./txt/cord-287372-ya5uvoki.txt === reduce.pl bib === id = cord-288644-ywaefpe8 author = Rodon, Jordi title = Pre-clinical search of SARS-CoV-2 inhibitors and their combinations in approved drugs to tackle COVID-19 pandemic date = 2020-10-20 pages = extension = .txt mime = text/plain words = 7571 sentences = 449 flesch = 50 summary = We have tested the antiviral activity of different clinically available compounds and their combinations by assessing their ability to inhibit viral induced cytopathic effect in vitro. Drug selection criteria first focused on compounds already being tested in clinical trials, along with well-known human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) protease inhibitors, as well as other compounds suggested to have potential activity against SARS-CoV-2 in molecular docking analysis or in vitro assays. Additional Food and Drug Administration (FDA)-approved compounds previously used to abrogate viral entry via clathrin-mediated endocytosis were also tested in this SARS-CoV-2-induced cytotoxicity assay (Supp . Cytopathic effect on Vero E6 cells exposed to a fixed concentration of SARS-CoV-2 in the presence of increasing concentrations of plitidepsin and its combinations with hydroxychloroquine and remdesivir. cache = ./cache/cord-288644-ywaefpe8.txt txt = ./txt/cord-288644-ywaefpe8.txt === reduce.pl bib === id = cord-293274-ysr1l557 author = Perisé-Barrios, Ana Judith title = Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date = 2020-09-22 pages = extension = .txt mime = text/plain words = 4140 sentences = 267 flesch = 54 summary = Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. cache = ./cache/cord-293274-ysr1l557.txt txt = ./txt/cord-293274-ysr1l557.txt === reduce.pl bib === id = cord-293428-8hj06hzt author = Yang, Jianling title = Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model date = 2020-04-24 pages = extension = .txt mime = text/plain words = 1855 sentences = 88 flesch = 53 summary = To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung. Recent 99 publications have demonstrated that chloroquine (CQ) and hydroxychloroquine (HCQ) 100 efficiently inhibited SARS-CoV-2 infection in vitro assay (7-9). The data suggest that HCQ was 127 demonstrated to be much less toxic than CQ, at least at certain key tissues (heart, liver, 128 kidney, and lung). However, the tissue trough concentration of 197 HCQ in lung is the highest level (25.633 μg/ml) compared with liver, kidney and heart 198 (Table 2 and Figure 4 ). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting 286 SARS-CoV-2 infection in vitro cache = ./cache/cord-293428-8hj06hzt.txt txt = ./txt/cord-293428-8hj06hzt.txt === reduce.pl bib === id = cord-295560-0rpguepv author = Yan, Kexin title = Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives date = 2020-10-14 pages = extension = .txt mime = text/plain words = 1883 sentences = 99 flesch = 55 summary = The assay clearly illustrated the anti-viral activity of remdesivir, a drug known to inhibit SARS-CoV-2 replication. Here we describe a simple rapid bioassay for drug screening using Vero 20 E6 cells and inhibition of cytopathic effects (CPE) measured using crystal violet staining. A key refinement involves a simple growth assay to identify drug concentrations that 23 cause cellular stress or "cytomorbidity", as distinct from cytotoxicity or loss of viability. A key refinement involves a simple growth assay to identify drug concentrations that 23 cause cellular stress or "cytomorbidity", as distinct from cytotoxicity or loss of viability. Thus a drug that has no specific anti-viral activity, but that 52 is able to induce cellular stress, may therefore inhibit virus replication non-specifically and generate 53 a potential false positive in the screening assay. A simple rapid bioassay for screening drugs for potential antiviral activity against SARS-CoV-2 72 is to determine whether the drug can inhibit virus-induced cytopathic effects (CPE) in Vero E6 cells. cache = ./cache/cord-295560-0rpguepv.txt txt = ./txt/cord-295560-0rpguepv.txt === reduce.pl bib === id = cord-294120-8fxrqorg author = Guebre-Xabier, Mimi title = NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge date = 2020-08-19 pages = extension = .txt mime = text/plain words = 866 sentences = 78 flesch = 64 summary = title: NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. And, hACE2 receptor 158 inhibition titers of 649, 1,410, and 1,320 in 2.5, 5, and 25 µg NVX-CoV2373 dose groups 159 respectively were 5.2 -11.2-fold higher than in convalescent sera ( Figure 1C) . Finally, 160 SARS-CoV-2 GMT neutralization antibody titers of 17,920 -23,040 CPE 100 in 161 immunized macaques, were 7.9 -10.1-fold higher than in convalescent sera ( Figure 162 1D) . To evaluate the potential efficacy of NVX-CoV2373 vaccine, macaques were 165 challenged with SARS-CoV-2 virus in upper and lower airways. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 214 elicits immunogenicity in baboons and protection in mice These interests do not alter the authors adherence to policies on 209 sharing data and materials. cache = ./cache/cord-294120-8fxrqorg.txt txt = ./txt/cord-294120-8fxrqorg.txt === reduce.pl bib === id = cord-295545-ruxz77i8 author = Hennighausen, Lothar title = Activation of the SARS-CoV-2 receptor Ace2 by cytokines through pan JAK-STAT enhancers date = 2020-05-11 pages = extension = .txt mime = text/plain words = 1660 sentences = 108 flesch = 55 summary = The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. The presence of pan JAK-STAT components in mammary alveolar cells and in Type II Pneumocytes combined with the autoregulation of both STAT1 and STAT5 suggests a prominent role of cytokine signaling pathways in cells targeted by SARS-CoV-2. A study in pneumocytes demonstrated that ACE2 expression is induced by interferons (Ziegler, 2020) , possibly through the transcription factors Signal Transducer and Activator of Transcription (STAT) 1 and 2, as the authors suggest. Ace2 mRNA levels vary widely between cell types, with high expression detected in lactating mammary and intestinal tissues ( Figure 1A -B) and Type II Pneumocytes (Ziegler, 2020) . To explore the possibility that Ace2 gene expression in SARS-CoV-2 target cells is regulated not only by interferons but also by a range of cytokines through the family of STAT transcription factors, we mined available scRNA-seq data (Ziegler, 2020) (Table 1) . cache = ./cache/cord-295545-ruxz77i8.txt txt = ./txt/cord-295545-ruxz77i8.txt === reduce.pl bib === id = cord-288824-sygnmiun author = Lam, SD title = SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals date = 2020-08-19 pages = extension = .txt mime = text/plain words = 7353 sentences = 412 flesch = 54 summary = To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We correlated changes in the energy of the complex with changes in the structure of ACE2, chemical properties of residues in the binding interface, and experimental COVID-19 infection phenotypes from in vivo and in vitro animal studies. We used multiple methods to assess the relative change in binding energy (ΔΔG) of the SARS-CoV-2 S-protein:ACE2 complex following mutations in DC residues and DCEX residues that are likely to influence binding. Irrespective of host, the SARS-CoV-2 spike receptor binding domain is conserved (Fig. 4b) across tested human and animal associated SARS-CoV-2, suggesting mutations in the RBD are not required for infections observed in non-human species to date. cache = ./cache/cord-288824-sygnmiun.txt txt = ./txt/cord-288824-sygnmiun.txt === reduce.pl bib === id = cord-292985-w62xaa4f author = Römer, Rudolf A. title = Flexibility and mobility of SARS-CoV-2-related protein structures date = 2020-07-12 pages = extension = .txt mime = text/plain words = 5201 sentences = 341 flesch = 61 summary = We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. 34 We have performed our analysis through multiple conformational steps starting from the crystal structures of SARS-CoV-2-related proteins as currently deposited in the PDB. In Fig. 1 (a) we see that for the crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (PDB:6m3m), the largest rigid cluster in the pristine structure, i.e. at E cut = 0, largely remains rigid through the dilution process of consecutively lowering E cut values. Last, a protein with 2nd-order rigidity should have the most complex behaviour in terms of flexibility since new possible mobility can be expected throughout the range of E cut values. Moving along directions proposed by an elastic normal model analysis of the crystal structure, we can therefore construct possible motion trajectories that are fully consistent with the bond network and steric constraints. cache = ./cache/cord-292985-w62xaa4f.txt txt = ./txt/cord-292985-w62xaa4f.txt === reduce.pl bib === id = cord-292862-ezrkg0dc author = Myerson, Jacob W. title = Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment date = 2020-04-18 pages = extension = .txt mime = text/plain words = 14275 sentences = 744 flesch = 46 summary = We show that polystyrene nanoparticles and five liposome formulations do not accumulate in injured lungs, indicating that nanostructures that are not based on protein are not intrinsically drawn to marginated neutrophils in acute inflammation. 6, 10, 14, 18 Single cell suspensions prepared from mouse lungs were probed by flow cytometry to further characterize pulmonary neutrophils in naïve mice and in mice following LPS-induced inflammation. The protein component of each particle was labeled with 125 I for tracing in biodistributions, and assessed 30 minutes after IV administration of NPs. Both absolute LDNG lung uptake and ratio of lung uptake to liver uptake registered a ~25-fold increase between naïve control and LPS-injured animals (Figure 2A , Supplementary Table 1) . As with LDNGs and albumin NPs in Figure 2C -H, single cell suspensions were prepared from LPS-inflamed and naïve control lungs after circulation of fluorescent DBCO-IgG liposomes. cache = ./cache/cord-292862-ezrkg0dc.txt txt = ./txt/cord-292862-ezrkg0dc.txt === reduce.pl bib === id = cord-292670-12prczym author = Urra, José Miguel title = The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms date = 2020-07-14 pages = extension = .txt mime = text/plain words = 2099 sentences = 115 flesch = 44 summary = Humans evolved by losing the capacity to synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti-α-Gal IgM/IgG antibodies produced in response to bacterial microbiota. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with α-Gal epitopes to modify the microbiota and increase the α-Gal-induced protective immune response and reduce the severity of COVID-19. Although more severe symptoms have been associated with elderly patients, herein older 199 patients were recorded in the hospitalized and not the ICU group (p < 0.001; Table 1 The serum IgA, IgE, IgM and IgG antibody response to α-Gal was characterized in healthy 226 individuals and COVID-19 patients at different disease stages (Figures 2 and 3a) . cache = ./cache/cord-292670-12prczym.txt txt = ./txt/cord-292670-12prczym.txt === reduce.pl bib === id = cord-293826-2p7dqacd author = Lee, Cheryl Yi-Pin title = Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant date = 2020-10-09 pages = extension = .txt mime = text/plain words = 1314 sentences = 84 flesch = 54 summary = Given that a majority of the developing antibody-mediated therapies 68 and serological assays are based on the S antigen of the original Wuhan reference 69 sequence, it is crucial to determine if humoral immunity acquired from the original 70 SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against 71 the novel prevailing D614G variant. Given that a majority of the developing antibody-mediated therapies 68 and serological assays are based on the S antigen of the original Wuhan reference 69 sequence, it is crucial to determine if humoral immunity acquired from the original 70 SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against 71 the novel prevailing D614G variant. Overall, our study shows that the D614G mutation on the S protein does not 150 impact SARS-CoV-2 neutralization by the host antibody response, nor confer viral 151 resistance against the humoral immunity. cache = ./cache/cord-293826-2p7dqacd.txt txt = ./txt/cord-293826-2p7dqacd.txt === reduce.pl bib === id = cord-297021-fzfl08qa author = Manomaipiboon, Anan title = The new silicone N99 half-piece respirator, VJR-NMU N99: A novel and effective tool to prevent COVID-19 date = 2020-07-23 pages = extension = .txt mime = text/plain words = 3108 sentences = 181 flesch = 57 summary = To meet the need for FFRs during a pandemic, Navamindradhiraj University has invented a new model of silicone N99 facepiece respirator by using the silicone mask and the HEPA filter normally used in the operating room (CareStar or SafeStar, Draeger, Germany) (Fig 1) . As required by Occupational Safety and Health Administration OSHA) [7] , the half piece respirators need to pass the fit test to identify those individuals who do not achieve a sufficiently good fit necessary for adequate protection. The study was conducted to achieve two specific research objectives: (1) to investigate the fit characteristics of the novel silicone mask and whether the strap adjustment can help reduce the face-seal leakage; and (2) to determine the level of performance by measuring the inward leakage of the generated aerosols with a new filter and a used filter (for up to 24 h). cache = ./cache/cord-297021-fzfl08qa.txt txt = ./txt/cord-297021-fzfl08qa.txt === reduce.pl bib === id = cord-297754-d4xnj551 author = Aktas, Emre title = Bioinformatic Analysis Reveals That Some Mutations May Affect On Both Spike Structure Damage and Ligand Binding Site date = 2020-09-03 pages = extension = .txt mime = text/plain words = 2891 sentences = 346 flesch = 75 summary = It might be thought like case of influenza(where mutations slowly accumulate in the hemagglutinin protein during a flu season),and there is a complex interplay between mutations that can confer immune resistance to the virus, and the fitness landscape of the particular variant in which they arise [5] .The SARS-CoV-2 ,which mutation rate rate remarkable high and many variation have already characterized, has shown to have gone through certain mutations both in its structural and non structural proteins within several months while spreading throughout the world [8, 10] I focused my study on both determining some mutations that occurred based on the regions and evaluating whether this new mutation had an effect on the shapes of spike proteins.Besides I tried to predict that how mutations affect on ligand site. cache = ./cache/cord-297754-d4xnj551.txt txt = ./txt/cord-297754-d4xnj551.txt === reduce.pl bib === id = cord-296187-nnv2e7gr author = Mulgaonkar, Nirmitee title = Bcr-Abl tyrosine kinase inhibitor imatinib as a potential drug for COVID-19 date = 2020-08-18 pages = extension = .txt mime = text/plain words = 4943 sentences = 306 flesch = 57 summary = The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered as a potential target for drug development. Based on in silico screening followed by in vitro studies, here we report that the existing FDA-approved Bcr-Abl tyrosine kinase inhibitor, imatinib, inhibits SARS-CoV-2 with an IC50 of 130 nM. We provide evidence that although imatinib binds to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein with an affinity at micromolar, i.e., 2.32 ± 0.9 μM levels, imatinib does not directly inhibit the spike RBD:ACE2 interaction – suggesting a Bcr-Abl kinase-mediated fusion inhibition mechanism is responsible for the inhibitory action. This study utilizes in silico methodology followed by in vitro experimental validation to screen existing FDA-approved small molecule drugs specific to the RBD of the spike protein of SARS-CoV-2 to identify repurposable drugs targeting further clinical validation. cache = ./cache/cord-296187-nnv2e7gr.txt txt = ./txt/cord-296187-nnv2e7gr.txt === reduce.pl bib === id = cord-297775-ug4ovsws author = Hosie, Margaret J title = Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK date = 2020-09-23 pages = extension = .txt mime = text/plain words = 1997 sentences = 118 flesch = 54 summary = High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. Recent reports from Dutch mink farms of both mink-to-cat and mink-tohuman transmission of the virus provide support for this scenario (5, 9) We used a range of laboratory techniques to show that two domestic cats from households with suspected cases of COVID-19, and which displayed either mild or severe respiratory disease, were infected with SARS-CoV-2. As we do not have the owner's virus sequence, we cannot determine whether the observed mutations in cat 2's viral genome arose in a human prior to transmission. Table 1 details the SNPs observed in the cat 2 viral genome, and their frequency in the existing UK human population and among existing feline SARS-CoV-2 sequences. cache = ./cache/cord-297775-ug4ovsws.txt txt = ./txt/cord-297775-ug4ovsws.txt === reduce.pl bib === id = cord-297787-t9neub6d author = Fu, Ziyang title = Structural basis for the inhibition of the papain-like protease of SARS-CoV-2 by small molecules date = 2020-07-18 pages = extension = .txt mime = text/plain words = 2152 sentences = 149 flesch = 64 summary = The co-crystal structure of SARS-CoV-2 PLpro-C111S in complex with GRL0617 suggests that GRL0617 is a non-covalent inhibitor. The antiviral activity of GRL0617 reveal that PLpro is a promising drug target for therapeutically treating COVID-19. The in-vitro 85 IC50 of GRL0617 against SARS-COV-2 PLpro was 2.1 ± 0.2 μM, suggesting a promising lead 86 compound and therefore it was subjected to further structural and mechanistic studies ( Fig. 2A) . Taken together, our NMR and X-ray analysis indicates that GRL0617 162 is a potent PPI (protein-protein interaction) inhibitor for PLpro blocking the binding of ISG15. Our co-crystal structure of PLpro C111S in complex with the potent 175 inhibitor GRL0617 validated that SARS-COV-2 PLpro is a druggable target. Based on the structure, GRL0617 resides in the S3/S4 site of PLpro, naturally it will also 179 inhibit the processing of viral polyproteins of SARS-CoV-2 since these viral polyproteins share the 180 same substrate cleavage sequence with Ub and ISG15. The SARS-coronavirus papain-like 257 protease: structure, function and inhibition by designed antiviral compounds cache = ./cache/cord-297787-t9neub6d.txt txt = ./txt/cord-297787-t9neub6d.txt === reduce.pl bib === id = cord-296997-ba7f2mf3 author = Sikora, Mateusz title = Map of SARS-CoV-2 spike epitopes not shielded by glycans date = 2020-07-03 pages = extension = .txt mime = text/plain words = 5818 sentences = 371 flesch = 55 summary = To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. Our simulation system contained four membrane-embedded SARS-CoV-2 S proteins assembled from resolved structures where available and models for the missing parts (SI Appendix, Fig. S5 ). In the ray analysis, we illuminated the protein model by diffuse light; in the Fab docking analysis, we performed rigid body Monte Carlo simulations of S and the SARS-CoV-2 antibody CR3022 Fab to determine the steric accessibility to an antibody Fab. To account for protein and glycan mobility, we performed both analyses individually for 4 × 193 snapshots taken at 10 ns time intervals from the 1.93 µs MD simulation with four glycosylated S proteins. cache = ./cache/cord-296997-ba7f2mf3.txt txt = ./txt/cord-296997-ba7f2mf3.txt === reduce.pl bib === id = cord-296657-mymndjvd author = Higuchi, Yusuke title = High affinity modified ACE2 receptors prevent SARS-CoV-2 infection date = 2020-09-16 pages = extension = .txt mime = text/plain words = 3509 sentences = 195 flesch = 51 summary = The extracellular domain of modified ACE2 fused to the Fc region of the human immunoglobulin IgG1 had stable structure and neutralized SARS-CoV-2 pseudotyped lentivirus and authentic virus with more than 100-fold lower concentration than wild-type. Engineering ACE2 decoy receptors with directed evolution is a promising approach to develop a SARS-CoV-2 neutralizing drug that has affinity comparable to monoclonal antibodies yet displaying resistance to escape mutations of virus. Three cycles of screening resulted in an identification of mutant ACE2 clones with more than 100-fold higher binding affinity to the RBD and lower half-maximal inhibitory concentration (IC50) for SARS-CoV-2 pseudotyped lentivirus as well as authentic virus. We engineered ACE2 to bind the RBD of the SARS-CoV-2 spike protein with the combination of surface display of mutagenized library and fluorescence-activated cell sorting (FACS) to perform the evolution in 293T human cells. cache = ./cache/cord-296657-mymndjvd.txt txt = ./txt/cord-296657-mymndjvd.txt === reduce.pl bib === id = cord-297684-9q3oopaz author = Dobaño, Carlota title = Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens date = 2020-06-12 pages = extension = .txt mime = text/plain words = 5198 sentences = 226 flesch = 41 summary = The Receptor-Binding Domain (RBD) of the spike (S) glycoprotein of SARS-CoV-2, the leading vaccine candidate target, was selected as the primary antigen to develop the initial qSAT assay because (i) S is one of the most immunogenic surface proteins together with the nucleocapsid protein (N) (20) (ii) RBD is the fragment of the virus that mediates binding to the host receptor ACE2 in the lung cells (21) (iii) antibodies to RBD correlate with neutralizing antibodies (20)(22) that could be associated with protection based on studies of other coronaviruses and animal models (23) (24) (25) (26) , and (iv) an ELISA based on this same protein has received FDA approval for COVID-19 serology (11) . We developed three novel multiplex immunoassays for quantifying IgM, IgA and IgG to eight SARS-CoV-2 protein constructs and evaluated by machine learning classification algorithms the performance of several isotype/antigen combinations to detect any positive antibody response to infection, obtaining specificities of 100% and sensitivities of 94.94% (≥14 days since symptoms onset) or 96.08% (≥21 days since symptoms onset), and very high predictability (AUC ≥0.99). cache = ./cache/cord-297684-9q3oopaz.txt txt = ./txt/cord-297684-9q3oopaz.txt === reduce.pl bib === id = cord-296981-tded20ih author = Gilmore, Kerry title = In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2 date = 2020-10-05 pages = extension = .txt mime = text/plain words = 3162 sentences = 174 flesch = 50 summary = We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). annua extracts, as well as pure artemisinin, artesunate, and artemether are active against SARS-CoV-2 in vitro. To initially screen whether extracts and pure artemisinin were active against SARS-CoV-2, their antiviral activity was tested by pretreating VeroE6 cells at different time points during 120 minutes with selected concentrations of the extracts or compounds prior to infection with the first European SARS-CoV-2 isolated in München (SARS-CoV-2/human/Germany/BavPat 1/2020). cache = ./cache/cord-296981-tded20ih.txt txt = ./txt/cord-296981-tded20ih.txt === reduce.pl bib === id = cord-296268-kb7fgfaq author = Mendonça, Luiza title = SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date = 2020-11-05 pages = extension = .txt mime = text/plain words = 2647 sentences = 161 flesch = 57 summary = Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Understanding the genome 27 replication, assembly and egress of SARS-CoV-2, a multistage process that involves different 28 cellular compartments and the activity of many viral and cellular proteins, is critically Krios to identify each individual infected cell (39.2 % for MOI of 0.1 and 45.4% for MOI 124 0.5) where cryoET tilt series were collected at the cell periphery. The grids were then 125 transferred to a FIB/SEM dualbeam instrument and the same infected cells were subjected to 126 either serial cryoFIB/SEM volume imaging (Zhu et al., 2021) or cryoFIB milling of cellular 127 lamellae where additional cryoET tilt series were collected (Sutton et al., 2020) . cache = ./cache/cord-296268-kb7fgfaq.txt txt = ./txt/cord-296268-kb7fgfaq.txt === reduce.pl bib === id = cord-296007-1gsgd22t author = Mohseni, Amir Hossein title = Inferring MHC interacting SARS-CoV-2 epitopes recognized by TCRs towards designing T cell-based vaccines date = 2020-09-12 pages = extension = .txt mime = text/plain words = 2327 sentences = 110 flesch = 64 summary = Our TCR-pMHC models predicted that position 2 of the homologous peptide antigens ( Figure 1A ) related 2 2 0 to TCR-pMHC complex of SARS-CoV-2 as well as SARS-CoV and bat-CoV N proteins prefers the 2 2 1 hydrophobic amino acid residues (e.g. Ile, Leu, Met, and Phe), and the second position of these hit peptides 2 2 2 is an hydrophobic amino acid residue Pro forming five strong VDW forces with residues Y99, V67, M45, 2 2 3 Y7, and F9 and two H-bonds with residues K66 and E63 on MHC molecule ( Figure S2A , left). Visualization of interactions in the atomic level structure of a TCR-pMHC complex in the hit peptide of 2 4 9 SARS-CoV-2 N protein for HLA-E ( Figure S3C ) within 20 and 8 Å was generated on-the-fly using of the homologous peptide antigens of all queries has no detectable binding to both MHC and TCR. cache = ./cache/cord-296007-1gsgd22t.txt txt = ./txt/cord-296007-1gsgd22t.txt === reduce.pl bib === id = cord-296237-i9cti2ok author = Díez, José-María title = Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date = 2020-06-19 pages = extension = .txt mime = text/plain words = 3741 sentences = 220 flesch = 51 summary = Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. Recently, cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2, and MERS-CoV has been reported with currently available intravenous immunoglobulins (IVIG) such as Gamunex-C and Flebogamma DIF 19 . In this study, the neutralization capacity of the IVIG products Gamunex-C and Flebogamma DIF against these epidemic human coronaviruses -SARS-CoV, SARS-CoV-2, and MERS-CoV-was evaluated. Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2, and MERS-CoV by: i) ELISA techniques; and ii) well-stablished neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT50 titers ranging from 4.5 to >5 (Figure 2 ). cache = ./cache/cord-296237-i9cti2ok.txt txt = ./txt/cord-296237-i9cti2ok.txt === reduce.pl bib === id = cord-297826-2nruf2g7 author = Tian, Jing-Hui title = SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice date = 2020-06-30 pages = extension = .txt mime = text/plain words = 2660 sentences = 171 flesch = 60 summary = In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). Mice 171 immunized with 10 μg dose of NVX-CoV2373/Matrix-M induced antibodies that blocked 172 hACE2 receptor binding to S-protein and virus neutralizing antibodies 21-28-days after 173 a single priming dose ( Fig. 4B and 4C ). Importantly, we found the frequency 254 of IFN-γ + , TNF-α + , and IL-2 + cytokine-secreting CD4 + and CD8 + T cells was 255 significantly higher (p <0.0001) in spleens from the NVX-CoV2373/Matrix-M immunized 256 mice compared to mice immunized without adjuvant ( Fig. 6B and 6C) . Anti-S protein IgG titers were detected within 21-days of a single priming immunization 288 in animals immunized with NVX-CoV2373/Matrix-M across all the dose levels (GMT = 289 1,249-19,000). cache = ./cache/cord-297826-2nruf2g7.txt txt = ./txt/cord-297826-2nruf2g7.txt === reduce.pl bib === id = cord-297747-kifqgskc author = Lupala, Cecylia S. title = Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein date = 2020-03-27 pages = extension = .txt mime = text/plain words = 4522 sentences = 231 flesch = 57 summary = Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. When this study was started, neither the crystal structure of the SARS-CoV-2 spike protein nor the RBD segment were determined, so the homology modeling approach was applied to construct the model of the SARS-CoV-2 spike RBD in complex with the human ACE2 binding domain (denoted as CoV2-RBD/ACE2 in the following). Although the crystal structure and the predicted model of the CoV2-RBD/ACE2 complex provide important information about the binding interactions at the molecular interfaces, MD simulations can extend the knowledge to a dynamics regime in a fully solvated environment. cache = ./cache/cord-297747-kifqgskc.txt txt = ./txt/cord-297747-kifqgskc.txt === reduce.pl bib === id = cord-298716-pubhq564 author = Bryche, Bertrand title = Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters date = 2020-06-16 pages = extension = .txt mime = text/plain words = 3558 sentences = 212 flesch = 56 summary = title: Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria. We measured the OE thickness, the OSN cilia quality (based on Golf staining) and the immune cell infiltration of the olfactory mucosa (based on the Iba1 staining) on 6 images per animal taken from 3 different slides spread along the nasal cavity. Two recent reports indicate that olfactory neurons in hamster (Sia et al., 2020) and respiratory cells in ferret (Ryan et al., 2020) may be the target of SARS-CoV-2 but these studies did not focus on the nasal cavity and they did not use double staining to clearly identify the infected cells in the OE. cache = ./cache/cord-298716-pubhq564.txt txt = ./txt/cord-298716-pubhq564.txt === reduce.pl bib === id = cord-295765-c7o2ukm6 author = Silvas, Jesus A. title = Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication date = 2020-07-20 pages = extension = .txt mime = text/plain words = 2234 sentences = 145 flesch = 53 summary = VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. As SARS-CoV-2 replication 174 damages the cell monolayer, impedance measurements decrease over time, providing a detailed 175 assessment of infection kinetics. Based on the toxicity window of 1-20 221 h.p.t. determined with the VPS34 inhibitors, neither Triacsin C nor Orlistat induced early 222 cytotoxic effects, even at the highest concentrations of 50uM and 500uM, respectively ( Figure 223 3A and 3C). Here, we demonstrate that two VPS34 inhibitors, Orlistat, and Triacsin C each have clear effects 308 on SARS-CoV-2 replication and the morphology of viral replication centers. In contrast, the compounds did not exhibit any activity against 384 SARS-CoV-2 in Vero E6 cells whereas Triacsin C did. cache = ./cache/cord-295765-c7o2ukm6.txt txt = ./txt/cord-295765-c7o2ukm6.txt === reduce.pl bib === id = cord-298321-8871aifz author = Laamarti, Meriem title = Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum date = 2020-07-01 pages = extension = .txt mime = text/plain words = 2142 sentences = 123 flesch = 58 summary = The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Our recent study (13) based on the analysis of 30,983 genomes of SARS-CoV-2 variants belonging to 80 countries, revealed 5.67% of total mutations with a frequency greater than 1% of all the sequences analyzed suggesting that this virus is not yet adapted to its host. In all Moroccan SARS-CoV-2 genomes, the analysis of genetic variants revealed 61 mutations compared to the reference sequence (Fig 1) , including 29 non-syn(Fig 2A) . cache = ./cache/cord-298321-8871aifz.txt txt = ./txt/cord-298321-8871aifz.txt === reduce.pl bib === id = cord-295257-iguhy1z8 author = Calcagnile, Matteo title = ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study date = 2020-04-24 pages = extension = .txt mime = text/plain words = 4785 sentences = 253 flesch = 49 summary = SARS-CoV-2 and respiratory syndrome corona virus (SARS-CoV) Spike proteins share very high phylogenetic similarities (99%), and, indeed, both viruses exploit the same human cell receptor namely angiotensin-converting enzyme 2 (ACE2), a transmembrane enzyme whose expression dominates on lung alveolar epithelial cells 6, 15, 16 . In this study we have used a combination of in silico tools to analyze the possible impact of ACE2 single-nucleotide polymorphisms (SNPs) on the interaction with SARS-CoV-2 Spike glycoprotein. Results indicate that some residues of the ACE2 interface, which are involved in the interaction with SARS-CoV-2 Spike glycoprotein can actually fluctuate (Fig. 5cd ). Indeed, in the rodent blockade of the renin-angiotensin-aldosterone system limits the acute lung injury induced by the SARS-CoV-1 spike protein 49 , suggesting that if ACE2 function is preserved (because of increased baseline expression, as especially seen in pre-menopausal women), clinical course of infection might be less severe. cache = ./cache/cord-295257-iguhy1z8.txt txt = ./txt/cord-295257-iguhy1z8.txt === reduce.pl bib === id = cord-294275-pp0vlaye author = Li, Jingjing title = Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow date = 2020-06-03 pages = extension = .txt mime = text/plain words = 2367 sentences = 152 flesch = 55 summary = Here, we propose a method to detect SARC-Cov-2 infection within two hours combined with Loop-mediated Isothermal Amplification (LAMP) reaction and nanopore Flongle workflow. Here, we use nanopore Flongle workflow combined with LAMP reaction to propose a faster and more convenient method to detect SARS-CoV-2 and other respiratory viruses in two hours. This study presents a LAMP based method combined with nanopore Flongle rapid realtime sequencing workflow to detect COVID-19 as low as 3.25×10^2 copies/mL of SARS-CoV-2 in both laboratory and wild-caught environment. To test the limit of detection, the amplification products of dilution gradient 3.25×10^4, 3.25 × 10^3, 1.1 × 10^3, 6.5 × 10^2, 3.25 × 10^2 copies/mL and negative control total 12 samples were constructed another barcoding library (Oxford Nanopore, SQK-RBK004) as described above and sequenced using a PromethION flowcell to achieve more data. The study design ( Figure 2 ) for SARS-CoV-2 detection is based on LAMP rapid amplification of specific genes and sequenced by nanopore Flongle workflow. cache = ./cache/cord-294275-pp0vlaye.txt txt = ./txt/cord-294275-pp0vlaye.txt === reduce.pl bib === id = cord-298326-f5q7j3iu author = Nick, Benjamin C. title = Identification of a critical horseshoe-shaped region in the nsp5 (Mpro, 3CLpro) protease interdomain loop (IDL) of coronavirus mouse hepatitis virus (MHV) date = 2020-06-19 pages = extension = .txt mime = text/plain words = 2755 sentences = 118 flesch = 54 summary = In this study, we describe the identification of an essential, conserved horseshoe-shaped region in the nsp5 interdomain loop (IDL) of mouse hepatitis virus (MHV), a common coronavirus replication model. Structural modeling and sequence analysis of these sites in other coronaviruses, including all 7 human coronaviruses, suggests that the identified structure and sequence of this horseshoe regions is highly conserved and may represent a new, non-active-site regulatory region of the nsp5 (3CLpro) protease to target with coronavirus inhibitors. To evaluate whether any of 207 the recovered MHV nsp5 IDL mutants may exhibit a temperature-sensitive phenotype, we 208 performed an efficiency of plating (EOP) analysis by comparing the titers of each IDL virus by 209 plaque assay determined at a physiologic (37°C) and elevated temperature (40°C) (Fig. 3A) . cache = ./cache/cord-298326-f5q7j3iu.txt txt = ./txt/cord-298326-f5q7j3iu.txt === reduce.pl bib === id = cord-299737-r34d0rx7 author = Grant, Paul R title = Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic date = 2020-04-08 pages = extension = .txt mime = text/plain words = 1383 sentences = 78 flesch = 63 summary = The standard molecular diagnostic test is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). We have developed a simplified qRT-PCR assay that removes the need for an RNA extraction process and can be run on a real-time thermal cycler. The standard molecular diagnostic test for this virus is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). Using the same primers and probes, we have now developed a qRT-PCR that can be run on a real-time thermal cycler without the need for an RNA extraction process. Direct addition of samples to the qRT-PCR without extraction with a diagnostic sensitivity of 98.0%, specificity of 100% and accuracy of 98.8% compared to the method on the Panther Fusion. Many laboratories use real-time thermal cyclers, so this method can be used to increase national screening capacity without the need for other specialized equipment or RNA extraction reagents. cache = ./cache/cord-299737-r34d0rx7.txt txt = ./txt/cord-299737-r34d0rx7.txt === reduce.pl bib === id = cord-296649-h6oyjz56 author = Scherf-Clavel, Oliver title = Tissue Level Profiling of SARS-CoV-2 antivirals in mice to predict their effects: comparing Remdesivir’s active metabolite GS-441 524 vs. the clinically failed Hydroxychloroquine date = 2020-11-06 pages = extension = .txt mime = text/plain words = 5076 sentences = 263 flesch = 53 summary = In this study, an adapted mouse model was chosen to demonstrate its suitability to provide sufficient information on the model substances GS-441 524 and HCQ regarding plasma concentration and distribution into relevant tissues a prerequisite for treatment effectiveness. Blood and organ samples were taken at several time points and drug concentrations were quantified in plasma and tissue homogenates by two liquid chromatography/tandem mass spectrometry methods. For GS-441 524, measured tissue concentrations exceeded the reported in vitro EC50 values by more than 10-fold and in consideration of its high efficacy against feline infectious peritonitis, GS-441 524 could indeed be effective against SARS-CoV-2 in vivo. The value obtained from our experiments falls in that range and is comparable to the V z obtained in mice from blood concentrations and to plasma V z measured in humans (see Table 4 ). cache = ./cache/cord-296649-h6oyjz56.txt txt = ./txt/cord-296649-h6oyjz56.txt === reduce.pl bib === id = cord-297786-jz1d1m2e author = Hasan, Md. Mahbub title = Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date = 2020-08-26 pages = extension = .txt mime = text/plain words = 3271 sentences = 187 flesch = 54 summary = Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Then, we studied the variants present in different isolates of Bangladesh to investigate the pattern of mutations, identify UMs, and discuss the pseudo-effect of these mutations on the structure and function of encoded proteins, with their role in pathogenicity. To understand the SARS-CoV-2 viral transmission in Bangladesh, we performed phylogenetic analysis on the selected 207 viral genomes reported from different districts of Bangladesh along with selected 467 globally submitted sequences as reported from 42 countries and 6 continents ( Figure 1 ). cache = ./cache/cord-297786-jz1d1m2e.txt txt = ./txt/cord-297786-jz1d1m2e.txt === reduce.pl bib === id = cord-300423-q2i328sz author = Bai, Lei title = Co-infection of influenza A virus enhances SARS-CoV-2 infectivity date = 2020-10-14 pages = extension = .txt mime = text/plain words = 1470 sentences = 106 flesch = 64 summary = Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. The results demonstrate that the pre-infection of 57 IAV strongly enhances the infectivity of SARS-CoV-2 by boosting viral entry in the cells 58 and by elevating viral load plus more severe lung damage in infected mice. We 75 further tested more cell lines to show that the enhancement of the pSARS-CoV-2 infectivity 76 by IAV was a general effect although the increased folds were different (lower basal level 77 of infectivity, higher enhancement fold) (Fig.1D ). We found that the pre-infection of IAV 80 strongly increased the copy numbers of the SARS-CoV-2 genome (E and N genes) in both 81 cell lysates and supernatants of A549 (~15 folds) (Fig.1F) . The histological data in Fig. 2D further illustrated that IAV and 98 SARS-CoV-2 co-infection induced more severe lung pathologic changes with massive 99 infiltrating cells and obvious alveolar necrosis as compared to SARS-CoV-2 single 100 infection or mock infection. cache = ./cache/cord-300423-q2i328sz.txt txt = ./txt/cord-300423-q2i328sz.txt === reduce.pl bib === id = cord-297044-tpp40j0g author = Jin, Zhenming title = Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur date = 2020-04-28 pages = extension = .txt mime = text/plain words = 1146 sentences = 84 flesch = 62 summary = title: Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease 24 (M pro ). Here the X-ray crystal structure of M pro in complex with Carmofur reveals that 25 the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, 26 whereas its fatty acid tail occupies the hydrophobic S2 subsite. Here, we present the 1.6 Å X-ray crystal structure of SARS-CoV-2 M pro in complex 49 with Carmofur (Fig. 1b, domain II feature the catalytic dyad residues Cys145 and His41 (Fig. 1c, d) . Here we determined the inhibitory 94 effect of Carmofur against SARS-CoV-2 infection on Vero E6 cells, as previously 95 described 20 (Fig. 2) . cache = ./cache/cord-297044-tpp40j0g.txt txt = ./txt/cord-297044-tpp40j0g.txt === reduce.pl bib === id = cord-300783-pvn2qq0f author = Sadykov, Mukhtar title = Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction date = 2020-08-07 pages = extension = .txt mime = text/plain words = 933 sentences = 91 flesch = 61 summary = title: Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanisms are still largely unknown. Remarkably, by simply ordering SARS-CoV-2 genomes by their date of collection, we find a progressive increase of C-to-U substitutions resulting in 5'-UCG-3' motif reduction that in turn have reduced the CpG frequency over just a few months of observation. Our results thus link the dynamics of target sequences in the viral genome for two known host molecular defense mechanisms, mediated by the APOBEC and ZAP proteins. One such 34 mechanism is the CpG dinucleotide reduction observed in many single-stranded RNA 35 fraction of the observed C>U changes represent multiple, independent events ( Figure S3 ). CpG Dinucleotides in SARS-CoV-2 Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host 396 antiviral defense Multi-site co-398 mutations and 5'UTR CpG immunity escape drive the evolution of SARS-CoV-2 cache = ./cache/cord-300783-pvn2qq0f.txt txt = ./txt/cord-300783-pvn2qq0f.txt === reduce.pl bib === id = cord-300194-nsp53lv6 author = Rath, Soumya Lipsa title = Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations date = 2020-06-19 pages = extension = .txt mime = text/plain words = 4302 sentences = 226 flesch = 54 summary = Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. and S2 domains individually, with respect to the starting structure, to understand the ause for higher R S values o served at and igure The R S values of S1 domain at and were found to e around nm nearly nm more than simulations at 1 and respe tively similar trend was o served in the R S of S domain ut the differen e in values was only 1 nm lthough in this study we haven't considered the bilayer lipid membrane of the SARS-COV-2 envelope inside which the Spike 9 glycoprotein resides, the S2 domain shows remarkable stability in its RMSD values ( Figure 2 ). cache = ./cache/cord-300194-nsp53lv6.txt txt = ./txt/cord-300194-nsp53lv6.txt === reduce.pl bib === id = cord-301535-eui41zyg author = Chandler-Brown, Devon title = A Highly Scalable and Rapidly Deployable RNA Extraction-Free COVID-19 Assay by Quantitative Sanger Sequencing date = 2020-04-10 pages = extension = .txt mime = text/plain words = 4143 sentences = 228 flesch = 52 summary = This assay uses the addition of a frame-shifted spike-in, a modified PCR master mix, and custom Sanger sequencing data analysis to detect and quantify SARS-CoV-2 RNA at a limit of detection comparable to existing qPCR-based assays, at 10-20 genome copy equivalents. Crucially, our assay was able to detect SARS-CoV-2 RNA from viral particles suspended in transport media that was directly added to the PCR master mix, suggesting that RNA extraction can be skipped entirely without any degradation of test performance. Quantitative analysis of the Sanger sequence chromatogram gives qSanger an extremely high sensitivity and specificity for all positive results with a limit of detection of 10-20 genome copy equivalents (GCE), equivalent to gold-standard qPCR methods. To further evaluate the feasibility of a direct VTM, extraction-free method for Sars-CoV-2 detection, we also examined the ability of qSanger to quantify the amount of viral particles in the Seracare positive control specimens (Fig. 3B ). cache = ./cache/cord-301535-eui41zyg.txt txt = ./txt/cord-301535-eui41zyg.txt === reduce.pl bib === id = cord-300707-k9uk14b3 author = Bouwman, Kim M. title = Multimerization- and glycosylation-dependent receptor binding of SARS-CoV-2 spike proteins date = 2020-09-04 pages = extension = .txt mime = text/plain words = 2328 sentences = 176 flesch = 59 summary = Here we created monomeric and trimeric fluorescent RBD proteins, derived from adherent HEK293T, as well as in GnTI mutant cells, to analyze the effect of complex vs high mannose glycosylation on receptor binding. Our results show that fully glycosylated trimeric RBD proteins are attractive to analyze receptor binding and explore ACE2 expression profiles in tissues. The results demonstrate 104 that fully glycosylated trimeric SARS-CoV-2 RBD proteins reveal the 105 differences in ACE2 expression between cell cultures and tissue sections. A similar trend of binding intensities was observed for 214 monomeric, trimeric, and different N-glycosylated SARS-CoV-RBD proteins 215 fused to mOrange2 ( Fig S3A) . 226 227 To confirm our observations of different binding on tissues, we quantified the 228 intensities of the ACE2 antibody and SARS-CoV-1 and -2 RBD proteins, except 229 for the monomeric GnTI derived proteins as these were almost at the 230 background ( Fig 4D) . cache = ./cache/cord-300707-k9uk14b3.txt txt = ./txt/cord-300707-k9uk14b3.txt === reduce.pl bib === id = cord-301233-nenw0f81 author = Naydenova, Katerina title = Structural basis for the inhibition of the SARS-CoV-2 RNA-dependent RNA polymerase by favipiravir-RTP date = 2020-10-21 pages = extension = .txt mime = text/plain words = 4059 sentences = 217 flesch = 51 summary = Here we report the structure of favipiravir ribonucleoside triphosphate (favipiravir-RTP) in complex with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) bound to a template:primer RNA duplex, determined by electron cryomicroscopy (cryoEM) to a resolution of 2.5 Å. The structure reveals an unusual, non-productive binding mode of favipiravir-RTP at the catalytic site of SARS-CoV-2 RdRp which explains its low rate of incorporation into the RNA primer strand. Here we report the structure of the SARS-CoV-2 RdRp, comprising subunits nsp7, nsp8 and nsp12, in complex with template:primer double-stranded RNA and favipiravir ribonucleoside triphosphate (favipiravir-RTP), determined by cryoEM at 2.5Å resolution. In this study, we determined the cryoEM structure of favipiravir-RTP at the catalytic site of the SARS-CoV-2 RdRp, in complex with template:primer dsRNA, and investigated the influence of this nucleotide analogue inhibitor on RNA synthesis in vitro. cache = ./cache/cord-301233-nenw0f81.txt txt = ./txt/cord-301233-nenw0f81.txt === reduce.pl bib === id = cord-298242-iuskpoug author = Yu, Alvin title = A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion date = 2020-10-02 pages = extension = .txt mime = text/plain words = 3604 sentences = 204 flesch = 47 summary = Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. In this paper, we construct a largely "bottom-up" coarse-grained (CG) model of the SARS-CoV-2 virion from the currently available structural and atomistic simulation data on SARS-CoV-2 proteins. In this work, we detail several of our CG methods used to iteratively develop a CG model for the full SARS-CoV-2 virion, in which molecular interactions between CG particles are derived using a combination of phenomenological, experimental, and atomistic simulation approaches. In recent cryo-EM images of SARS-CoV-2 particles, the S1 domain of the S protein was found to transiently open and close in order to bind the ACE-2 receptor (3, 5) , which are subtle conformational changes that are difficult to sample in atomistic simulations. cache = ./cache/cord-298242-iuskpoug.txt txt = ./txt/cord-298242-iuskpoug.txt === reduce.pl bib === id = cord-300078-svu06v9c author = Haghani, Milad title = Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCov literature date = 2020-06-01 pages = extension = .txt mime = text/plain words = 6365 sentences = 298 flesch = 52 summary = To compare the scientometric aspects of the studies on SARS, MERS and Covid-19, three separate datasets of publications on these three topics were retrieved from Scopus through three separate search strategies. Figures A1 and A2 in the Appendix illustrate the map associated with the SARS literature overlaid respectively with the average year of publication and average number of citations associated with the studies where these keywords have occurred. Maps of term occurrences based on the analysis of the title and abstract of studies on SARS, MERS and Covid-19 have also been presented in Figures 7, 8 and 9 respectively. An inspection of the maps overlaid with the average year of publications for SARS and MERS in Figures A1 and A3 in the Appendix suggests that, on average, this cohort of studies are generally the last to emerge in the published domain compared to the two other major clusters, but they receive relatively high citations on average (according to Figures A2, A4 and A6). cache = ./cache/cord-300078-svu06v9c.txt txt = ./txt/cord-300078-svu06v9c.txt === reduce.pl bib === id = cord-302146-51hof7it author = Cross, Thomas J. title = Sequence characterization and molecular modeling of clinically relevant variants of the SARS-CoV-2 main protease date = 2020-05-15 pages = extension = .txt mime = text/plain words = 3668 sentences = 196 flesch = 50 summary = Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mpro variants, constituting all clinically observed mutations in this protein as of April 29, 2020. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery. Molecular modeling is an important tool for guiding inhibitor discovery, making it possible to evaluate large numbers of candidate drugs in silico to select experimental targets; however, standard approaches screen against only one version of the protein, typically the reference or wild-type (WT) sequence. Here we characterize all 79 known variants of M pro as of 29 April, 2020, and analyze trends in amino acid substitutions and the resulting structural changes using network analysis and molecular modeling. Analysis of active site networks (ASN) from M pro variants suggests differences in active site flexibility and cohesion that may serve to guide the design of robust, mutation-resistant inhibitors. cache = ./cache/cord-302146-51hof7it.txt txt = ./txt/cord-302146-51hof7it.txt === reduce.pl bib === id = cord-302608-fw4pmaoc author = Huang, Jiao-Mei title = Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date = 2020-03-19 pages = extension = .txt mime = text/plain words = 1890 sentences = 125 flesch = 57 summary = However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. The host specificity of virus particle is determined by amino acid sequence of RBD and is usually dissimilar among different CoVs. Therefore, RBD is a core determinant for tissue tropism and host range of CoVs. This article presents SARS-CoV-2 phylogenetic trees, comparison and analysis of genome, spike protein, and RBD amino acid sequences of different CoVs, deducing source and etiology of COVID-19 and evolutionary relationship among SARS-CoV-2 in human. The S-protein amino acid sequence identity between SARS-CoV-2 and related beta-CoVs showed that bat/Yunnan/RaTG13 shares highest similarity of 97.43%. cache = ./cache/cord-302608-fw4pmaoc.txt txt = ./txt/cord-302608-fw4pmaoc.txt === reduce.pl bib === id = cord-304544-tqtdjh2m author = Enes, Ak title = Transcriptional response of signalling pathways to SARS-CoV-2 infection in normal human bronchial epithelial cells date = 2020-06-20 pages = extension = .txt mime = text/plain words = 3745 sentences = 189 flesch = 49 summary = Comparison of transcriptome of NHBE cells 24 hours after mock-infection and SARS-CoV-2 infection demonstrated that most genes that respond to infection were upregulated (320 genes) rather than being downregulated (115 genes).While upregulated genes were enriched in signalling pathways related to virus response, downregulated genes are related to kidney development. Although virus entry protein ACE2 has low expression in NHBE cells, pathogen response pathways are strongly activated within 24 hours of infection. Upregulated MMPs and chemokines demonstrate the response generated by NHBE cells to trigger the immune system, these two subgroups of genes are further discussed below comparatively in SARS-CoV-2 and H1N1 infection. Interestingly, none of the IL-17 ligands were expressed in detectable amounts in NHBE cells, and none of the ligands or receptors were upregulated in response to virus infection, therefore the positive feedback loop is likely to be initiated by activation of NFκB via other signalling pathways. cache = ./cache/cord-304544-tqtdjh2m.txt txt = ./txt/cord-304544-tqtdjh2m.txt === reduce.pl bib === id = cord-303069-ss6g3jkg author = Jakhar, Renu title = An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2 date = 2020-05-26 pages = extension = .txt mime = text/plain words = 3379 sentences = 202 flesch = 52 summary = A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. The aim of this study is to analyze envelope protein strains using in silico approaches looking for the conservancy, which is further studied to predict all potential epitopes that can be used after in vitro and in vivo confirmation as a therapeutic peptide vaccine [22, 23, 24] . Envelope protein from the SARS-CoV-2 was analyzed using the IEDB MHC-1 binding prediction tool to predict the T cell epitope suggested interacting with different types of MHC Class I alleles. Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus cache = ./cache/cord-303069-ss6g3jkg.txt txt = ./txt/cord-303069-ss6g3jkg.txt === reduce.pl bib === id = cord-305589-ofpna4k1 author = Schubert, Katharina title = SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation date = 2020-07-07 pages = extension = .txt mime = text/plain words = 4090 sentences = 229 flesch = 55 summary = By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. Based on these results we assembled in vitro a 40S-Nsp1 complex and determined its structure at 2.8 Å resolution using cryo-EM (Extended Data Fig. 2 ). As observed in the high-resolution structure of the 40S-Nsp1 complex, the C-terminal part of Nsp1 in the mRNA entrance channel (Fig. 1e ) folds into two helices that interact with h18 of the 18S rRNA as well as proteins uS3 in the head and uS5 and eS30 in the body, respectively ( Fig. 1f; Fig. 2a ). Our structural data suggest that SARS-CoV-2 Nsp1 inhibits translation by sterically occluding the entrance region of the mRNA channel and interfering with binding of cellular mRNAs (Fig. 4a,b) . cache = ./cache/cord-305589-ofpna4k1.txt txt = ./txt/cord-305589-ofpna4k1.txt === reduce.pl bib === id = cord-302733-rfuyd041 author = Dellicour, Simon title = A phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages date = 2020-10-21 pages = extension = .txt mime = text/plain words = 3727 sentences = 165 flesch = 41 summary = At the country scale, our spatially-explicit phylogeographic analyses highlight that the national lockdown had a relatively low impact on both the lineage dispersal velocity and the long-distance dispersal events within Belgium. At the country scale, our spatially-explicit phylogeographic analyses highlight that the national lockdown had a relatively low impact on both the lineage dispersal velocity and the long-distance dispersal events within Belgium. We generated a time-scaled phylogenetic tree using a rapid maximum likelihood approach 16 and subsequently ran a preliminary discrete phylogeographic analysis along this tree to identify internal nodes and descending clades that likely correspond to distinct introductions into the Belgian territory ( Fig. 1, S2 ). We used the continuous diffusion model 13 available in BEAST 1.10 14 to perform a spatially-explicit (or "continuous") phylogeographic reconstruction of the dispersal history of SARS-CoV-2 lineages in Belgium. cache = ./cache/cord-302733-rfuyd041.txt txt = ./txt/cord-302733-rfuyd041.txt === reduce.pl bib === id = cord-298172-iyxyennq author = Guo, Youjia title = Potent mouse monoclonal antibodies that block SARS-CoV-2 infection date = 2020-10-02 pages = extension = .txt mime = text/plain words = 4557 sentences = 295 flesch = 49 summary = Various recombinant monoclonal antibodies of human origin that neutralize SARS-CoV-2 infection have been isolated from convalescent patients and will be applied as therapies and prophylaxis. Here, we produced mouse anti-SARS-CoV-2 spike monoclonal antibodies that exhibit not only robust performance in immunoassays including western blotting, ELISA, immunofluorescence, and immunoprecipitation, but also neutralizing activity against SARS-CoV-2 infection in vitro. Among them, two antibodies were shown to attenuate the interaction of spike proteins with ACE2 and neutralized infection of VeroE6/TMPRSS2 cells by SARS-CoV-2. Mice were immunized with these recombinant spike proteins to generate antibodies against the SARS-CoV-2 virus, followed by cell fusion to generate a hybridoma-producing antibody. The performance of our antibodies in IP experiments prompted us to examine whether they were capable of inhibiting spike-ACE2 binding or even neutralizing SARS-CoV-2 infection. Our antibodies, S1D7 and S3D8, have been shown to attenuate the interaction of spike proteins with ACE2 and neutralize infection of VeroE6/TM2 cells by SARS-CoV-2. cache = ./cache/cord-298172-iyxyennq.txt txt = ./txt/cord-298172-iyxyennq.txt === reduce.pl bib === id = cord-303832-1kcqhgjw author = Dai, Manman title = Long-term survival of salmon-attached SARS-CoV-2 at 4°C as a potential source of transmission in seafood markets date = 2020-09-06 pages = extension = .txt mime = text/plain words = 834 sentences = 49 flesch = 66 summary = Several outbreaks of COVID-19 were associated with seafood markets, raising concerns that fish-attached SARS-CoV-2 may exhibit prolonged survival in low-temperature environments. ABSTRACT 21 Several outbreaks of COVID-19 were associated with seafood markets, raising concerns that 22 fish-attached SARS-CoV-2 may exhibit prolonged survival in low-temperature environments. In this study, we detected the titer (50% tissue culture infectious dose/mL, TCID 50 /mL) of 35 viable SARS-CoV-2 attached on salmon or untreated SARS-CoV-2 in culture medium stored at 36 4°C, the temperature in refrigerators or cold rooms for the temporary storage of fish, or 25°C, the 37 regular room temperature, respectively, using end-point titration assay on Vero E6 cells as 38 described previously (8). As shown in Figure A and B, salmon-attached SARS-CoV-2 remained 39 viable at 4°C and 25°C for 8 and 2 days, respectively, while the untreated SARS-CoV-2 in 40 culture medium remained infectious at 4°C and 25°C for more than 8 days. cache = ./cache/cord-303832-1kcqhgjw.txt txt = ./txt/cord-303832-1kcqhgjw.txt === reduce.pl bib === id = cord-304792-8sdxqmkb author = Khan, Md. Abdullah-Al-Kamran title = SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date = 2020-05-08 pages = extension = .txt mime = text/plain words = 2983 sentences = 207 flesch = 48 summary = title: SARS-CoV-2 proteins exploit host's genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. We have utilized KEGG mapper tool (Kanehisa and Sato, 2020) for the mapping of 197 deregulated genes SARS-CoV-2 interacting host proteins in different cellular pathways. cache = ./cache/cord-304792-8sdxqmkb.txt txt = ./txt/cord-304792-8sdxqmkb.txt === reduce.pl bib === id = cord-300272-95o8yd7h author = Thépaut, Michel title = DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist date = 2020-08-10 pages = extension = .txt mime = text/plain words = 6862 sentences = 356 flesch = 53 summary = In the context of the current COVID-19 pandemic, attention is now focused on the SARS-CoV-2 virus Zhou et al., 2020) .Coronaviruses use a homotrimeric glycosylated spike (S) protein protruding from their viral envelope to interact with cell membranes and promote fusion upon proteolytic activation. Additionally, in the case of SARS-CoV-2, a new paradigm is needed to untangle the complex clinical picture, resulting in a vast range of possible symptoms and in a spectrum of disease severity associated on one hand with active viral replication and cell infection through interaction with ACE2 along the respiratory tract, and, on the other hand, to the development of excessive immune activation, i.e. the so called "cytokine storm", that is related to additional tissue damage and potential fatal outcomes. These observations prompted us to investigate the potential interaction of C-type lectins receptors, notably DC/L-SIGN with SARS-CoV-2, through glycan recognition of the spike envelope glycoprotein, as well at their potential role in SARS-CoV-2 transmission. cache = ./cache/cord-300272-95o8yd7h.txt txt = ./txt/cord-300272-95o8yd7h.txt === reduce.pl bib === id = cord-303399-s1hbpvn7 author = Straus, Marco R. title = SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses date = 2019-08-31 pages = extension = .txt mime = text/plain words = 6424 sentences = 466 flesch = 64 summary = SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. https://doi.org/10.1101/752592 doi: bioRxiv preprint vivo situation and requires validation by expressing the full-length fusion proteins in a cell culture model 3 to test cleavage and cleavage inhibition of the respective protease (39). To test SPINT2-mediated cleavage inhibition of full-length HA we expressed the HAs of A/CA/04/09 9 (H1N1), A/x31 (H3N2) and A/Shanghai/2/2013 (H7N9) in 293T cells and added recombinant matriptase or 10 KLK5 protease that were pre-incubated with 10nM or 500nM SPINT2. To understand whether SPINT2 was able to inhibit or reduce the growth of virus in a cell culture 20 model over the course of 48 hours we transfected cells with human TMPRSS2 and human matriptase, two 21 major proteases that have been shown to be responsible for the activation of distinct influenza A subtype 22 cache = ./cache/cord-303399-s1hbpvn7.txt txt = ./txt/cord-303399-s1hbpvn7.txt === reduce.pl bib === id = cord-303868-aes92l6s author = Steffen, Tara L. title = The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera date = 2020-08-22 pages = extension = .txt mime = text/plain words = 6098 sentences = 300 flesch = 46 summary = In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. This suggests that polyclonal antibody binding to the RBD domain of the spike protein represents the key target of neutralizing antibody to SARS-CoV-2 after natural infection. Most importantly, our antigen-specific antibody depletion approach demonstrated that the RBD domain of the spike protein is responsible for 70% +/-18.9% of the human polyclonal neutralizing antibody activity to spike after natural SARS-CoV-2 infection. Although our study shows that the dominant target of IgG neutralizing antibody response after natural SARS-CoV-2 infection is the RBD domain of the spike protein, we have evaluated a limited number (n=10) of patients by antigen-specific antibody depletion. cache = ./cache/cord-303868-aes92l6s.txt txt = ./txt/cord-303868-aes92l6s.txt === reduce.pl bib === id = cord-305054-4d84b2g6 author = Liu, Yuan title = The selection of reference genome and the search for the origin of SARS-CoV-2 date = 2020-08-11 pages = extension = .txt mime = text/plain words = 2166 sentences = 140 flesch = 60 summary = The assembly obtained using RaTG13 as reference showed better statistics in total length and N50 than the assembly guided by SARS-CoV-2, indicating that RaTG13 maybe a better reference for assembling CoV in pangolin or other potential intermediate hosts. Zhang, Wu, and Zhang [13] re-analyzed the RNA-Seq reads from two pangolins carrying coronavirus using reference-guided de novo assembly method, with Wuhan-Hu-1 as the reference genome. They also performed RNA sequencing in five archived pangolins samples from Guangdong, and assembled the genomes using WIV04, another SARS-CoV-2 genome from human, as reference genome. Using de novo assembly method, they obtained viral genome that showed 90.32% and 90.24% of whole genome identify to Wuhan-Hu-1and Bat-CoV RaTG13, respectively. RaTG13, which is a bat CoV, had 1,287 reads mapped to it, and the resulting assembly has total length of 21,925 and N50 of 1,428. cache = ./cache/cord-305054-4d84b2g6.txt txt = ./txt/cord-305054-4d84b2g6.txt === reduce.pl bib === id = cord-307536-qeo5dfxg author = Feng, Ye title = Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) date = 2020-06-30 pages = extension = .txt mime = text/plain words = 998 sentences = 69 flesch = 58 summary = title: Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19. Based on both the epitope counts and HLA score, we 250 eventually selected 13 T-cell epitopes-only vaccine peptides. cache = ./cache/cord-307536-qeo5dfxg.txt txt = ./txt/cord-307536-qeo5dfxg.txt === reduce.pl bib === id = cord-300847-ycuiso0g author = Li, Wei title = Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models date = 2020-06-02 pages = extension = .txt mime = text/plain words = 2801 sentences = 172 flesch = 55 summary = We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. By using phage display we have previously identified a number of potent fully human mAbs (m396, m336, m102.4) against emerging viruses including severe acute respiratory syndrome coronavirus (SARS-CoV) (4) , Middle East respiratory syndrome coronavirus (MERS-CoV) (5) and henipaviruses (6, 7) , respectively, which are also highly effective in animal models of infection (8) (9) (10) (11) ; one of them was administered on a compassionate basis to humans exposed to henipaviruses and successfully evaluated in a clinical trial (12) . Thus, to generate high affinity and safe mAbs we used eight very large (size ~ 10 11 clones each) naive human antibody libraries in Fab, scFv or VH format using PBMCs from 490 individuals total obtained before the SARS-CoV-2 outbreak. cache = ./cache/cord-300847-ycuiso0g.txt txt = ./txt/cord-300847-ycuiso0g.txt === reduce.pl bib === id = cord-305496-t8ykkekl author = Stone, E. Taylor title = Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay date = 2020-08-21 pages = extension = .txt mime = text/plain words = 7227 sentences = 391 flesch = 60 summary = One such tool for evaluating neutralizing antibody response is a 88 plaque/focus neutralization reduction test (PRNT/FRNT), which evaluates the ability of polyclonal 89 sera samples to prevent or reduce infection of a cell monolayer in vitro. We examined the impact of cell density on foci formation for both Vero WHO and Vero E6 cells 144 by plating identical dilutions of SARS-CoV-2 virus stocks on 96-well plates seeded with differing 145 numbers of WHO or E6 cells (3 × 104, 1.5 × 104 or 3 × 104 cells/well) one day prior to infection 146 of the cell monolayer. To determine the optimal time frame for infection of SARS-CoV-2 on a Vero WHO cell 172 monolayer to form individual foci, we tested a variety of incubation times. The FFA relies on an immunostaining protocol of an infected cell monolayer in order to 197 quantify infectious virus titer and is therefore dependent upon SARS-CoV-2-specific antibody 198 cache = ./cache/cord-305496-t8ykkekl.txt txt = ./txt/cord-305496-t8ykkekl.txt === reduce.pl bib === id = cord-308310-wtmjt3hf author = Zha, Lisha title = Development of a COVID-19 vaccine based on the receptor binding domain displayed on virus-like particles date = 2020-05-14 pages = extension = .txt mime = text/plain words = 2012 sentences = 110 flesch = 54 summary = Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro. The receptor binding domain (RBD) of the SARS spike protein binds to ACE2 and is an important target for neutralizing antibodies [5] [6] [7] . Hence, the RBD-CuMVTT vaccine candidate is able to induce high levels of SARS-CoV-2 neutralizing antibodies. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine cache = ./cache/cord-308310-wtmjt3hf.txt txt = ./txt/cord-308310-wtmjt3hf.txt === reduce.pl bib === id = cord-310752-zl2g9wqo author = Sato, Taku title = Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats date = 2020-05-15 pages = extension = .txt mime = text/plain words = 2135 sentences = 119 flesch = 48 summary = Methods To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry. Results Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Notably, strong co-expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal respiratory epithelium, trachea, bronchioles, alveoli, and the kidney. The strong co-expression of ACE2 and TMPRSS2 in the taste buds may explain the high incidence of ageusia or dysgeusia in patients with SARS-CoV-2 infection. Unlike that in the nasal respiratory epithelium, TMPRSS2 was more strongly expressed in the cytoplasm of tracheal epithelium, hence suggesting the trachea to be more prone to developing clinical symptoms after SARS-CoV-2 infection than the nasal tissue. cache = ./cache/cord-310752-zl2g9wqo.txt txt = ./txt/cord-310752-zl2g9wqo.txt === reduce.pl bib === id = cord-307504-cogk5kig author = Zhu, Yuanmei title = Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity date = 2020-03-28 pages = extension = .txt mime = text/plain words = 1946 sentences = 107 flesch = 51 summary = title: Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity. Then, we designed a HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly poent activities in inibibiting the SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus infection. Taken together, these results suggested that 128 SARS-CoV-2 might evolve an increased interaction between the HR1 and HR2 domains in 129 the S2 fusion protein thus critically determining its high fusogenic activity. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: 354 implications for virus fusogenic mechanism and identification of fusion inhibitors Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition 368 using spike protein heptad repeat-derived peptides Heptad repeat-derived peptides block protease-mediated direct entry from the cell surface of 371 severe acute respiratory syndrome coronavirus but not entry via the endosomal pathway cache = ./cache/cord-307504-cogk5kig.txt txt = ./txt/cord-307504-cogk5kig.txt === reduce.pl bib === id = cord-307811-6e3j0pn7 author = Hao, Wei title = Binding of the SARS-CoV-2 Spike Protein to Glycans date = 2020-07-02 pages = extension = .txt mime = text/plain words = 5665 sentences = 299 flesch = 54 summary = Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. Previous studies of many other viruses suggested that SARS-CoV-2 S protein may use other molecules on host cell surface as attachment factors to facilitate binding to the high-affinity receptor ACE2. 36 A recent study suggested that HS may bind to the receptor binding domain (RBD, the C-terminal region of the S1 subunit, Fig. 2 ) of the SARS-CoV-2 spike protein and change its conformation. 38 In this study, we systematically examined and compared the binding of the SARS-CoV-2 S protein subunits, full-length molecule and its trimer to different HS using microarray experiments (Fig. 2) . In addition to binding protein-based receptors, many viruses can interact with cell surface glycans, including GAGs and sialic acid-containing oligosaccharides. cache = ./cache/cord-307811-6e3j0pn7.txt txt = ./txt/cord-307811-6e3j0pn7.txt === reduce.pl bib === id = cord-307242-e20gtx0z author = Jegouic, Sophie M. title = Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping date = 2020-05-22 pages = extension = .txt mime = text/plain words = 3454 sentences = 177 flesch = 52 summary = Similar western blot analysis of total protein extracts following induction of logarithmic phase E.coli cultures with IPTG confirmed the expression of His-tagged S antigen of the predicted molecular weight in all cases ( Figure 3 , upper panel). Nevertheless, we found that S protein fragments prepared for gel electrophoresis using non-reducing loading buffer could be used successfully for epitope mapping of 2 S reactive monoclonal antibodies, 3G9, an unpublished mouse mAb generated to SARS S, and CR3022, a human mAb also isolated originally to SARS [19] but shown to cross-react with SARS-CoV-2. To provide an additional level of validation and to add epitope specificity to the data, 2 of the sera scoring positive by S1 ELISA were used as probes on western blots using full length S expressed in insect cells (cf. Optimization of the Production Process and Characterization of the Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain ( RBD219-N1 ), a SARS Vaccine Candidate cache = ./cache/cord-307242-e20gtx0z.txt txt = ./txt/cord-307242-e20gtx0z.txt === reduce.pl bib === id = cord-302160-4yfvspaq author = Ruetalo, Natalia title = Rapid and efficient inactivation of surface dried SARS-CoV-2 by UV-C irradiation date = 2020-10-07 pages = extension = .txt mime = text/plain words = 1853 sentences = 108 flesch = 56 summary = Strikingly, short exposure of high titer surface dried virus (3*10^6 IU/ml) with UV-C light (16 mJ/cm2) resulted in a total reduction of SARS-CoV-2 infectivity. We hence conducted a "real-life" application approach simulating the 66 inactivation of dried surface residing infectious SARS-CoV-2 by a mobile handheld UV-C 67 emitting device and an UV-C box designed to decontaminate medium-size objects. Simulating the situation that exhaled droplets or aerosols from infected 115 individuals contaminate surfaces, we produced a high-titer SARS-CoV-2 infectious stock and 116 dried 35µL of this stock corresponding to ~4*10^6 IU/ml in each well of a 6-well plate. Of note, even short UV-C treatment of the dried virus in the context of the moving "fast" 135 regimen completely inactivated SARS-CoV-2, as no infected cells were detected based on 136 fluorescence protein expression (Fig. 1b) . Altogether, our data 143 demonstrate that UV-C regimens that expose high-titer SARS-CoV-2 to doses down to 16 144 mJ/cm² are sufficient to achieve complete inactivation of the virus. cache = ./cache/cord-302160-4yfvspaq.txt txt = ./txt/cord-302160-4yfvspaq.txt === reduce.pl bib === id = cord-306901-uuwgpuhw author = Roy, Sylvie title = Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein date = 2020-09-16 pages = extension = .txt mime = text/plain words = 4215 sentences = 251 flesch = 58 summary = title: Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein Several investigational vaccines that have already been tested in animals and humans were able to induce neutralizing antibodies against the SARS-CoV-2 spike (S) protein, however protection and long-term efficacy in humans remain to be demonstrated. We have investigated if a virus-like particle (VLP) derived from Moloney murine leukemia virus (MLV) could be engineered to become a candidate SARS-CoV-2 vaccine amenable to mass production. High amounts of SARS-CoV-2 DS protein are incorporated into MLV VLPs released 142 from stable producer cells. A VLP-derived SARS CoV-2 vaccine will be a viable option if 143 sufficient amounts of S protein are incorporated at the surface of the released particles. In conclusion, we have developed and characterized a new MLV VLP platform that can 243 efficiently incorporate the S protein from SARS-CoV-2, and that has the potential to produce a pan-244 coronavirus vaccine. cache = ./cache/cord-306901-uuwgpuhw.txt txt = ./txt/cord-306901-uuwgpuhw.txt === reduce.pl bib === id = cord-311240-o0zyt2vb author = Motayo, Babatunde Olarenwaju title = Evolution and Genetic Diversity of SARSCoV-2 in Africa Using Whole Genome Sequences date = 2020-07-27 pages = extension = .txt mime = text/plain words = 3091 sentences = 167 flesch = 50 summary = Our study has revealed a rapidly diversifying viral population with the G614 spike protein variant dominating, we advocate for up scaling NGS sequencing platforms across Africa to enhance surveillance and aid control effort of SARSCoV-2 in Africa. The pathogen was later identified to be a novel coronavirus closely related to the severe acute respiratory syndrome virus (SARS), with a possible bat origin (Zhou et al, 2020) . This study was designed to determine to the genetic diversity and evolutionary history of genome sequences of SARSCoV-2 isolated in Africa. Results of recombination analysis of the African SARSCoV-2 (AfrSARSCoV-2) sequences against references whole genome sequences of SARS, Recombination signals were observed between the African SARSCoV-2 sequences and reference sequence (Major recombinant hCoV-19 Pangolin/Guangu P4L/2017; Minor parent hCoV-19 B batYunan/RaTG13) between the RdRP and S gene regions (Figure 2 ). cache = ./cache/cord-311240-o0zyt2vb.txt txt = ./txt/cord-311240-o0zyt2vb.txt === reduce.pl bib === id = cord-307701-fujejfwb author = Gaurav, Shubham title = Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date = 2020-06-07 pages = extension = .txt mime = text/plain words = 2069 sentences = 111 flesch = 54 summary = Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the novel human Corona Virus Disease COVID-19, first reported on November 17 th , 2019 in Wuhan, China [12] . In addition to structural and NSPs, SARS-CoV-2 genome also codes for at least two other viroporin candidates (other than the E protein), namely ORF3a and ORF8 [3] . Moreover, the 29-nucleotide deleted SARS CoV-1 strain had a 23-fold less viral replication as compared to its wild type, suggesting that this mutation effectively attenuated the virus. cache = ./cache/cord-307701-fujejfwb.txt txt = ./txt/cord-307701-fujejfwb.txt === reduce.pl bib === id = cord-309289-vm0k7hfx author = Rothan, Hussin A. title = The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date = 2020-04-14 pages = extension = .txt mime = text/plain words = 1463 sentences = 91 flesch = 46 summary = title: The FDAapproved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, antiinflammatory and anti-ROS properties. We investigated the anti-viral activity of auranofin against SARS-CoV-2 and its effect on virus-induced inflammation in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury. cache = ./cache/cord-309289-vm0k7hfx.txt txt = ./txt/cord-309289-vm0k7hfx.txt === reduce.pl bib === id = cord-310464-lkdkdque author = Rayko, Mikhail title = Quality control of low-frequency variants in SARS-CoV-2 genomes date = 2020-05-07 pages = extension = .txt mime = text/plain words = 1702 sentences = 109 flesch = 58 summary = During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. As a result of the collaborative efforts of the researchers worldwide, on April 14, 2020 it contained over 8,000 SARS-nCoV-2 genomes from different countries, sequenced and assembled using various technologies and approaches. GISAID database curators do a tremendous job of filtering submitted sequences, but sometimes it is difficult to distinguish real variants from errors, especially at the lack of information about coverage. Dataset 8,053 full-length (>29,000 bp) sequences of the SARS-CoV-2 were downloaded from the GISAID database ( www.epicov.org ) on April 14, 2020, including 5,556 genomes marked as "high coverage". Full table with percentage of singleton-containing genomes depending on sequencing and assembly method. cache = ./cache/cord-310464-lkdkdque.txt txt = ./txt/cord-310464-lkdkdque.txt === reduce.pl bib === id = cord-304356-jyp9gjh9 author = Grant, Rogan A. title = Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells date = 2020-08-05 pages = extension = .txt mime = text/plain words = 7453 sentences = 427 flesch = 44 summary = We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. b. Sankey diagram illustrating relationship between number of BAL samples from participants with COVID-19, other viral pneumonia, non-viral pneumonia (other pneumonia) and non-pneumonia controls 1) enrolled in the SCRIPT study (534 samples), 2) analyzed via flow cytometry (344 samples), 3) bulk RNA-seq on flow-sorted alveolar macrophages (243 samples) and 4) single-cell RNA-seq (6 samples). To define the immune cell profile over the course of severe SARS-CoV-2-induced pneumonia, we analyzed 116 samples from 61 patients with confirmed COVID-19 in our cohort. As our analysis of transcriptomic data from alveolar macrophages suggested that SARS-CoV-2 pneumonia is uniquely associated with the activation of pathways induced by interferons, we looked for the expression of type I interferons in our single cell dataset. cache = ./cache/cord-304356-jyp9gjh9.txt txt = ./txt/cord-304356-jyp9gjh9.txt === reduce.pl bib === id = cord-311114-ggcpsjk8 author = Radhakrishnan, Chandni title = Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date = 2020-09-09 pages = extension = .txt mime = text/plain words = 4383 sentences = 274 flesch = 52 summary = The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. In our analysis, we mapped the SARS-CoV-2 genetic variants obtained from Kerala genomes to the 132 primer or probes sequence and calculated the melting temperature (Tm) of the mutant with the wild type sequence. cache = ./cache/cord-311114-ggcpsjk8.txt txt = ./txt/cord-311114-ggcpsjk8.txt === reduce.pl bib === id = cord-312038-g76cpjp7 author = Brunaugh, Ashlee D. title = Broad-Spectrum, Patient-Adaptable Inhaled Niclosamide-Lysozyme Particles are Efficacious Against Coronaviruses in Lethal Murine Infection Models date = 2020-10-07 pages = extension = .txt mime = text/plain words = 11043 sentences = 517 flesch = 47 summary = Utilizing repurposed NIC, and with the goal of developing a therapeutically effective, rapidly scalable and globally distributable antiviral therapy to reduce the spread of SARS-CoV-2, we describe an inhalable NIC formulation that can be administered using three major models or respiratory tract delivery systems: DPI, nasal spray and nebulizer. At the highest dose tested (0.125 µg/mL NIC), Vero cells with an established MERS-CoV infection exhibited an 82.2% ± 0.8% decrease in viral load compared to untreated controls after 24-hours of exposure to NIC-hLYS particles ( Fig 1D) . While brain viral titres did not exhibit further reduction from levels noted in the preliminary efficacy study, the inoculation of Vero E6 cells with viral particles obtained from lung and brain homogenates of surviving animals resulted in no observation of CPE at any of the inoculum concentrations tested, which indicates that remaining viral particles were not active. cache = ./cache/cord-312038-g76cpjp7.txt txt = ./txt/cord-312038-g76cpjp7.txt === reduce.pl bib === id = cord-305858-gp1u4kh7 author = Song, Xiang title = High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients date = 2020-07-19 pages = extension = .txt mime = text/plain words = 4896 sentences = 268 flesch = 49 summary = To better understand the pathogenesis of COVID-19 and build up the host anti-viral immunity, we examined the levels of ACE2 expression on different types of immune cells including tissue macrophages. To determine whether platelets were directly targeted by SARS-CoV-2 or trigged by viral inflammatory reactions, we examined the ACE2 expression on the highly-purified CD41b + CD42a + platelets from human peripheral blood ( Figure 3A Our previous work established that platelets could release mitochondria contributing to the immune modulation and islet b-cell regeneration [13] . Thus, the virus-infected alveolar macrophages play a critical role in the pathogenesis of COVID-19 and SARS [28] [29] [30] and may recruit the lung infiltration of additional immune cells through predominantly releasing cytokines and chemokines [31, 32] , resulting in pulmonary edema and hypoxemia: the hallmark of acute respiratory distress syndrome (ARDS) ( Figure 6 ). cache = ./cache/cord-305858-gp1u4kh7.txt txt = ./txt/cord-305858-gp1u4kh7.txt === reduce.pl bib === id = cord-310230-9wfb43gt author = Ghorbani, Mahdi title = Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations date = 2020-06-27 pages = extension = .txt mime = text/plain words = 3479 sentences = 220 flesch = 56 summary = Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. 7 Based on the sequence similarity between RBD of nCOV-2019 and SARS-COV and also the tight binding between RBD of nCOV-2019 and ACE2, it is most probable that nCOV-2019 uses this receptor on human cells to gain entry into the body. The focus of this article is to elucidate the differences between the interface of SARS-COV and nCOV-2019 with ACE2 to understand with atomic resolution the interaction mechanism and hotspot residues at the RBD/ACE2 interface using long-timescale molecular dynamics (MD) simulation. The binding energetics between ACE2 and the RBD of SARS-COV, nCOV-2019 and all its mutant complexes were investigated by the MMPBSA method. Computational Simulations Reveal the Binding Dynamics between Human ACE2 and the Receptor Binding Domain of SARS-CoV-2 Spike Protein cache = ./cache/cord-310230-9wfb43gt.txt txt = ./txt/cord-310230-9wfb43gt.txt === reduce.pl bib === id = cord-302920-jkr438p9 author = Gasser, Romain title = Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 date = 2020-10-09 pages = extension = .txt mime = text/plain words = 423 sentences = 31 flesch = 48 summary = key: cord-302920-jkr438p9 title: Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 cord_uid: jkr438p9 Characterization of the humoral response to SARS-CoV-2, the etiological agent of Covid-19, is essential to help control the infection. In this regard, we and others recently reported that the neutralization activity of plasma from COVID-19 patients decreases rapidly during the first weeks after recovery. In this study, we selected plasma from a cohort of Covid-19 convalescent patients and selectively depleted immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of IgM. Decline of humoral 409 responses against SARS-CoV-2 Spike in convalescent individuals Potent neutralizing 413 antibodies from COVID-19 patients define multiple targets of vulnerability cache = ./cache/cord-302920-jkr438p9.txt txt = ./txt/cord-302920-jkr438p9.txt === reduce.pl bib === id = cord-311214-eqwxkwqa author = Kumar, Roshan title = Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date = 2020-04-16 pages = extension = .txt mime = text/plain words = 2724 sentences = 184 flesch = 60 summary = Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. A manually annotated reference database was generated using the Genbank 128 file of Severe acute respiratory syndrome coronavirus 2 isolate-SARS-CoV-129 2/SH01/human/2020/CHN (Accession number: MT121215) and open reading frames (ORFs) 130 were predicted against the formatted database using prokka (-gcode 1) [22] . All these isolates 189 were found to harbor 9 open reading frames coding for ORF1a (13218 bp) and ORF1b (7788 190 bp) polyproteins, surface glycoprotein or S-protein (3822 bp), ORF3a protein (828 bp Our analysis revealed that strains of human infecting SARS-CoV-2 are novel and highly 201 identical (>99.9%). In this study, the analysis was 358 performed on the genomes of the novel SARS-CoV-2 isolates recently reported from different 359 countries to understand viral pathogenesis. cache = ./cache/cord-311214-eqwxkwqa.txt txt = ./txt/cord-311214-eqwxkwqa.txt === reduce.pl bib === id = cord-311445-b6bc6vwd author = Bansal, Kanika title = Codon pattern reveals SARS-CoV-2 to be a monomorphic strain that emerged through recombination of replicase and envelope alleles of bat and pangolin origin date = 2020-10-12 pages = extension = .txt mime = text/plain words = 2749 sentences = 169 flesch = 60 summary = Systematic analysis of CUP of replicase (rdrp), spike, envelope (E), membrane glycoprotein (M), and nucleocapsid (N) encoding genes of SARS-CoV-2 from reported diverse lineages to suggest one-time host jump of a SARS-CoV-2 isolate into the human host. In contrast to human isolates, a high degree of variation in CUP of these genes suggests that bats, pangolins, and dogs are natural reservoirs of diverse strains. In the present study, we have focused on codon usage pattern (CUP) of SARS coronavirus from different hosts under debate (bat, pangolin, and dog) as a probable origin for SARS-CoV-2. However, another study comparing the codon usage pattern of SARS-CoV-2 with other betacoronaviruses suggested that current pandemic coronavirus is subjected to different evolutionary pressures (Gu et al., 2020) . The above analysis reveals single patterns for all five genes in different lineages of SARS-CoV-2 affirms a single event of host jump of codon-optimized SARS strain from its animal reservoir. cache = ./cache/cord-311445-b6bc6vwd.txt txt = ./txt/cord-311445-b6bc6vwd.txt === reduce.pl bib === id = cord-308428-zw26usmh author = Walter, Justin D. title = Highly potent bispecific sybodies neutralize SARS-CoV-2 date = 2020-11-10 pages = extension = .txt mime = text/plain words = 10526 sentences = 580 flesch = 54 summary = Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We identified a sybody pair (Sb#15 and Sb#68) that can bind simultaneously to the RBD, and block ACE2 binding, thereby neutralizing pseudotyped and live SARS-CoV-2 viruses. However, binders of the isolated RBD may not effectively engage the aforementioned pre-fusion conformation of the spike protein, which could account for the poor neutralization ability of recently described single-domain antibodies that were raised against the RBD of SARS-CoV-2 spike protein [29] . Since Sb#15 and Sb#68 can bind simultaneously to the RBD and the full-length spike protein, we mixed Sb#15 and Sb#68 together to investigate potential additive or synergistic neutralizing activity of these two independent sybodies. To gain structural insights into how Sb#15 and Sb#68 recognize the RBD, we performed single particle cryo-EM analysis of the spike protein in complex with the sybodies. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 cache = ./cache/cord-308428-zw26usmh.txt txt = ./txt/cord-308428-zw26usmh.txt === reduce.pl bib === id = cord-312305-ll29frwc author = Sun, Shihui title = Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date = 2020-11-11 pages = extension = .txt mime = text/plain words = 4720 sentences = 270 flesch = 52 summary = Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. We further characterized the in vivo replication dynamics of MASCp6 in both young and aged mice, and the results from qRT-PCR showed that high levels of SARS-CoV-2 subgenomic RNAs were persistent in the lung and tracheas till 4 day post infection (dpi) in aged mice (Fig. 1E) . The skewed age distribution of COVID-19 disease was reproduced in the MASCp36 infected mouse model where more severe symptoms were observed in aged mice when compared to young mice. In addition to the age-related skewed distribution of COVID-19, gender-related differences in distribution of COVID-19 disease is also recapitulated in this MASCp36 infected mouse model with increased susceptibility and enhanced pathogenicity observed in male mice when compared to their female counterparts. cache = ./cache/cord-312305-ll29frwc.txt txt = ./txt/cord-312305-ll29frwc.txt === reduce.pl bib === id = cord-310017-c8rd714a author = Popa, Alexandra title = Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date = 2020-07-17 pages = extension = .txt mime = text/plain words = 5572 sentences = 330 flesch = 49 summary = Moreover, we combined our deep viral genome sequencing data with epidemiologically identified chains of transmissions and family clusters together with biomathematical analyses to study genetic bottlenecks and the dynamics of genome evolution of SARS-CoV-2. We assembled SARS-CoV-2 genome sequences, constructed phylogenies and identified low 15 frequency mutations based on high-quality sequencing results with >5 million reads per sample and >80% of mapped viral reads (Fig. S2A-B) . Our pipeline was validated by experimental controls involving sample titration and technical sample replicates ( Fig. S2CTo investigate the link between local outbreaks in Austria and the global pandemic, we 20 performed phylogenetic analysis of 305 SARS-CoV-2 genomes from the Austrian cases (>96% genome coverage, >80% aligned viral reads) and 7,695 global genomes from the GISAID database (Fig. 1B, Table S1 ). 7 Dynamics of low frequency and fixed mutations in clusters Next, we sought to gain insights into the fundamental processes of SARS-CoV-2 infection by integrative analysis of viral genomes. cache = ./cache/cord-310017-c8rd714a.txt txt = ./txt/cord-310017-c8rd714a.txt === reduce.pl bib === id = cord-312228-wbyqmvhs author = Xiao, Minfeng title = Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples date = 2020-03-19 pages = extension = .txt mime = text/plain words = 3236 sentences = 194 flesch = 56 summary = Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. 90 Therefore, we aim to comprehensively compare the sensitivity, inter-individual (variant) and 91 intra-individual (iSNV) accuracy, and other general features of different approaches by sys-92 tematically utilizing ultra-high-throughput metatranscriptomic, hybrid capture-based, and 93 amplicon-based sequencing approaches to obtain genomic information of HCoV-19 from 94 serial dilutions of a cultured isolate and directly from clinical samples. We assessed the correlations between the HCoV-19 genome copies per mL in diluted 396 samples of cultured isolates and the minimum amount of sequencing data for amplicon-397 and capture-based methods using Pearson correlation coefficient (R) with the function 398 scatter from the R package ggpubr (v3.6.1) 38 . cache = ./cache/cord-312228-wbyqmvhs.txt txt = ./txt/cord-312228-wbyqmvhs.txt === reduce.pl bib === id = cord-312524-ee5xw1r8 author = Moustafa, Ahmed M. title = Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread date = 2020-06-08 pages = extension = .txt mime = text/plain words = 2058 sentences = 129 flesch = 61 summary = Here we present a rapid, whole genome, allele-based method (GNUVID) for assigning sequence types to sequenced isolates of SARS-CoV-2 sequences. Rapid sequencing of the SARS-CoV-2 pandemic virus has presented an 40 unprecedented opportunity to track the evolution of the virus and to understand the 41 emergence of a new pathogen in near-real time. Our panallelome approach to developing a whole genome (wgMLST) scheme for 58 SARS-CoV-2 uses a modified version of our recently developed tool, WhatsGNU [10], 59 to rapidly assign an allele number to each gene nucleotide sequence in the virus's 60 genome creating a sequence type (ST). We developed the GNU-based Virus IDentification (GNUVID) system as a tool 71 that automatically assigns a number to each unique allele of the 10 open reading 72 frames (ORFs) of SARS-CoV-2 ( Figure 1A) information. When the global region of origin for each genome sequence was mapped to 102 each CC there was a strong association of some CCs with certain geographical 103 locations. cache = ./cache/cord-312524-ee5xw1r8.txt txt = ./txt/cord-312524-ee5xw1r8.txt === reduce.pl bib === id = cord-306924-dw35dlx3 author = Wohlers, Inken title = COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans date = 2020-11-03 pages = extension = .txt mime = text/plain words = 798 sentences = 59 flesch = 54 summary = title: COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans Recent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. We show that (i) COVID-19-related genetic factors of Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic. However, as two positions carry protective alleles the risk probability of the 51 previously assessed Vindija Neanderthal haplotype is only 52%. 82 83 All human risk haplogroups differ from Neanderthal haplotypes (Fig. 1c) If this variant was causal (2% probability) using lead variants such as rs11385942 or 120 rs35044562 would incorrectly classify individuals carrying these haplogroups to be at 121 risk. The major genetic risk factor for severe COVID-19 is 142 inherited from Neanderthals cache = ./cache/cord-306924-dw35dlx3.txt txt = ./txt/cord-306924-dw35dlx3.txt === reduce.pl bib === id = cord-312473-7i7efdp2 author = Sidhom, John-William title = Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope date = 2020-06-20 pages = extension = .txt mime = text/plain words = 1181 sentences = 62 flesch = 46 summary = We first examined the distribution of TCRs within the McPas database over the types of pathogens present in the database and cross-referenced the SARS-CoV-2 specific TCRs into the McPas database ( Figure 1A) , and we noted that there was a statistically significant enrichment (from 17.3% to 32.9%) of SARS-CoV-2 specific TCRs that had known specificity to the immunodominant M1 GILGFVFTL epitope We then examined the distribution of TCRs within the ImmuneCode database across the various open readings frames (orfs) and mapped the M1 specific TCRs within this database ( Figure 1B) . In conclusion, while these results are preliminary in a small cohort of individuals, we have identified a set of TCRs that is known to both recognize an immunodominant epitope derived from Influenza and SARS-CoV-2, suggesting that immune control of one infection may play a role in the control of the other. cache = ./cache/cord-312473-7i7efdp2.txt txt = ./txt/cord-312473-7i7efdp2.txt === reduce.pl bib === id = cord-309411-2dfiwo65 author = Paris, Kristina A. title = Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology date = 2020-06-23 pages = extension = .txt mime = text/plain words = 4728 sentences = 256 flesch = 58 summary = On the other hand, the loss of this pH-switch, which sequence alignments show is unique to CoV2, eliminates the transition state and allows the virus to stay bound to the ACE2 receptor for time scales compatible with the recruitment of additional ACE2 receptors diffusing in the cell membrane. Work on SARS-CoV (CoV1) has already determined that the virus enters cells via receptormediated endocytosis in a pH-dependent manner (Wang et al., 2008) that is characterized by cotranslocation of the viral spike glycoprotein and its specific functional receptor, the angiotensinconverting enzyme 2 (ACE2), from the cell surface to early endosomes. This newly discovered difference in protein sequence in the receptor binding domain of the spike glycoprotein and its impact on receptor binding reveals a mechanism that allows SARS-CoV2 internalization to take advantage of the high expression of ACE2 in the nasal epithelium¾resulting in increased retention times in the upper respiratory tract and augmented infectivity. cache = ./cache/cord-309411-2dfiwo65.txt txt = ./txt/cord-309411-2dfiwo65.txt === reduce.pl bib === id = cord-310477-vniokol0 author = Pontes, Camila title = Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs date = 2020-08-21 pages = extension = .txt mime = text/plain words = 4371 sentences = 197 flesch = 46 summary = More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). In summary, the SDPs found within these β-CoV subgenera define a specific region of the receptor binding domains: they are part of, or in direct contact with, the ACE2 interacting surface ( A second S3Det analysis was performed on the full β-CoV MSA. On the other hand, the analysis performed on individual β-CoV subgenera, i.e. Sarbecovirus, Merbecovirus and Embecovirus subgroups, allowed a fine-grained classification into subfamily clusters that clearly reflect the functional diversification of the spike protein family, that is, the specificity to different host-cell receptors (Figure 2-3) . cache = ./cache/cord-310477-vniokol0.txt txt = ./txt/cord-310477-vniokol0.txt === reduce.pl bib === id = cord-309512-d8n9711b author = Bacus, Michael G. title = Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses date = 2020-05-05 pages = extension = .txt mime = text/plain words = 1025 sentences = 71 flesch = 50 summary = Emerging infectious diseases due to coronavirus (CoV) infections have received significant global attention in the past decade and have been linked to bats as the original source. As such, deviant patterns were observed such as for 2D-IV, wherein cross-taxon transmission due to overlap in bat habitats and geographic range among genetically divergent African bat hosts could have played a strong role on their shared CoV lineages. In fact, a few bat taxa especially the subfamily Pteropodinae were shown to host diverse groups of BetaCoVs. Therefore, ecological imbalances that disturb bat distribution may lead to loss of host specificity through cross-taxon transmission and multi-CoV infection. Importance Bat Betacoronaviruses (BetaCoVs) pose a significant threat to global public health and have been implicated in several epidemics such as the recent pandemic by severe acute respiratory syndrome coronavirus 2. Although bat BetaCoVs are host taxon-specific, their evolutionary pathways are different from evolution with its host. cache = ./cache/cord-309512-d8n9711b.txt txt = ./txt/cord-309512-d8n9711b.txt === reduce.pl bib === id = cord-311843-un6urdb1 author = Baray, Juwel Chandra title = BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response date = 2020-09-30 pages = extension = .txt mime = text/plain words = 3173 sentences = 230 flesch = 62 summary = title: BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response The anti-sera and purified IgGs from immunized mice on day 7 and 14 neutralized SARS-CoV-2 pseudovirus in ACE2-expressing HEK293 cells in a dose dependent manner. The reactivity of the sera from each 221 group of mice immunized with BANCOVID was measured against SARS-CoV-2 S antigen 222 (SinoBiologicals, China). Analysis revealed IgG binding against SARS-CoV-2 S protein 223 antigens in the sera of the immunized mice. Flow cytometric analysis of total T cell (CD4 + ) populations producing TFN alpha on mouse splenocyte upon SARS-CoV-2 S protein stimulation. Flow cytometric analysis of total T cell (CD4 + ) populations producing IL-6 on mouse splenocyte upon SARS-CoV-2 S protein stimulation. Flow cytometric analysis of total T cell (CD4 + ) populations producing IL-6 on mouse splenocyte upon SARS-CoV-2 S protein stimulation. cache = ./cache/cord-311843-un6urdb1.txt txt = ./txt/cord-311843-un6urdb1.txt === reduce.pl bib === id = cord-312702-fruzsn26 author = Finch, Courtney L. title = Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) date = 2020-05-14 pages = extension = .txt mime = text/plain words = 2785 sentences = 167 flesch = 46 summary = title: Characteristic and quantifiable COVID-19-like abnormalities in CTand PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) Based on the rather limited X-97 ray findings in the lungs of reported NHP models of SARS-CoV-2 infection with either 98 mild or no clinical signs (11, 25, 27-29), we turned to high-resolution chest CT and 99 Increases in PCLH or PCLH/LV 169 were not seen in the mock-exposed macaques over the entire study (Figure 8a A key advantage of quantifiable CT chest imaging readout over serial euthanasia 212 studies, in addition to potentially reduced experimental animal numbers, is the ability not 213 only to evaluate between-group differences, but also to compare severity and duration of 214 disease at higher resolution in single animals and even in isolated parenchymal areas 215 sequentially. follow-up confirmation of these pilot results in this model of mild-moderate COVID-19 233 is needed to further establish quantifiable lung CT as a reliable disease readout and to 234 forge imaging-pathologic correlates in macaques euthanized at peak radiographic 235 abnormality. cache = ./cache/cord-312702-fruzsn26.txt txt = ./txt/cord-312702-fruzsn26.txt === reduce.pl bib === id = cord-313571-umcbulcw author = Martínez-Murcia, Antonio title = In silico design and validation of commercial kit GPS™ CoVID-19 dtec-RT-qPCR Test under criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012 date = 2020-05-05 pages = extension = .txt mime = text/plain words = 1189 sentences = 85 flesch = 54 summary = title: In silico design and validation of commercial kit GPS™ CoVID-19 dtec-RT-qPCR Test under criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012 Background The Corona Virus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has become a serious infectious disease affecting human health worldwide and rapidly declared a pandemic by WHO. Objectives A few days later, when additional SARS-CoV-2 genome were retrieved, the kit GPS™ CoVID-19 dtec-RT-qPCR Test was designed to provide a highly specific detection method and commercially available worldwide. Results The GPS™ RT-qPCR primers and probe showed the highest number of mismatches with the closet related non-SARS-CoV-2 coronavirus, including some indels. As the number of genomes available rapidly expanded during last January, the GPS™ CoVID-19 230 dtec-RT-qPCR Test was based on a more specific target for SARS-CoV-2 detection, being this 231 company one of the pioneers marketing a PCR-kit for the CoVID-19 worldwide. cache = ./cache/cord-313571-umcbulcw.txt txt = ./txt/cord-313571-umcbulcw.txt === reduce.pl bib === id = cord-314072-av3r7it7 author = Liu, Zhuoming title = Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization date = 2020-11-08 pages = extension = .txt mime = text/plain words = 1105 sentences = 74 flesch = 54 summary = title: Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization To define the immune-mediated mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor binding domain (RBD) to generate 48 escape mutants. Although each mAb had unique resistance profiles, many shared residues within an epitope, as several variants were resistant to multiple mAbs. Remarkably, we identified mutants that escaped neutralization by convalescent human sera, suggesting that some humans induce a narrow repertoire of neutralizing antibodies. By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, we identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans. To select for SARS-CoV-2 S variants that escape neutralization, we used VSV-SARSas we isolated this mutation alone, and acquisition of the L517R substitution appeared to 141 increase viral fitness as judged by plaque morphology (Fig S2) . cache = ./cache/cord-314072-av3r7it7.txt txt = ./txt/cord-314072-av3r7it7.txt === reduce.pl bib === id = cord-313247-55loucvc author = Pipes, Lenore title = Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny date = 2020-10-07 pages = extension = .txt mime = text/plain words = 2546 sentences = 209 flesch = 64 summary = We investigate several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution. There are many different methods for inferring the root of a phylogenetic tree, but they largely depend on three possible sources of information: outgroups, the molecular clock, and non-reversibility. To investigate the possible rootings of the SARS-CoV-2 phylogeny we used six different methods and quantified the uncertainty in the placement of the root for each method on the inferred maximum likelihood topology. We note that while interpretation of bootstrap proportions in phylogenetics can be problematic (see Efron et al., 1996) we performed 1,000 parametric simulations using pyvolve (Spielman and Wilke, 2015) using maximum likelihood estimates, from the original data set, of the model of molecular evolution and the phylogenetic tree, including branch lengths (see Table S2 ). cache = ./cache/cord-313247-55loucvc.txt txt = ./txt/cord-313247-55loucvc.txt === reduce.pl bib === id = cord-311066-62edsbfc author = Cox, Brian J. title = Integration of viral transcriptome sequencing with structure and sequence motifs predicts novel regulatory elements in SARS-CoV-2 date = 2020-06-24 pages = extension = .txt mime = text/plain words = 2926 sentences = 172 flesch = 61 summary = Analysis of SARS-CoV-2 RNA sequencing data from whole RNA transcriptomes identified TRS dependent and independent transcripts. Integration of transcripts and 5'-UTR sequence motifs identified that the pentaloop and the stem-loop 3 were also located upstream of spliced genes. Some RNAs, especially non-coding RNAs, generally lack a poly-A tail, which could explain poor detection of TRS independent sgmRNAs. Using published sequencing data of ribosome depleted total RNA from SARS-CoV-2 infected cells and animals (Blanco-Melo et al., 2020) , I aligned these against the viral genome (Figure 2) . Using the aligned reads, I generated transcript models using stringtie, which identified multiple spliced species that aligned with the TRS-L templated events (Figure 2) . Split reads also identified TRS-independent sgmRNAs. In support of my observations on SARS-CoV-2, I also assessed SARS-CoV and MERs transcriptional data, two other human pathogenic CoV. I also identified the TIR motif, a novel sequence element (ATTGGC) flanking the spliced regions of TRS independent sgmRNAs in both SARS-CoV-2 and SARS-CoV. cache = ./cache/cord-311066-62edsbfc.txt txt = ./txt/cord-311066-62edsbfc.txt === reduce.pl bib === id = cord-309556-xv3413k1 author = Chow, Ryan D. title = The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date = 2020-04-15 pages = extension = .txt mime = text/plain words = 5761 sentences = 373 flesch = 53 summary = In aggregate, these analyses showed that the age-associated genes with functional roles in SARS-CoV are expressed in specific cell types of the human lung. Of note, the overlap between lung ageassociated genes and SARS-CoV-2 regulated genes was statistically significant across all 3 cell lines (Figure 6d-f) , suggesting a degree of similarity between the transcriptional changes associated with aging and with SARS-CoV-2 infection. Among the age-associated genes that were induced by SARS-CoV-2 infection, the majority of these genes increase in expression with age (Cluster 1) (Figure 6g-i) . To identify a consensus set of age-associated genes that are regulated by SARS-CoV-2 infection, we integrated the analyses from all 3 cell lines. By integrating these data with single cell transcriptomes of human lung tissue, we further pinpointed the specific cell types that normally express the age-associated genes. cache = ./cache/cord-309556-xv3413k1.txt txt = ./txt/cord-309556-xv3413k1.txt === reduce.pl bib === id = cord-311333-shvtfxog author = Fukumoto, Tatsuya title = Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification date = 2020-05-28 pages = extension = .txt mime = text/plain words = 414 sentences = 37 flesch = 70 summary = title: Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification The virus was detected in 53/71 fresh samples by the direct method and 55/71 corresponding frozen samples by the nCoV-DK. Concordance rates were 95.2% (95% CI, 83.8-99.4), 95.5% (95% CI, 77.2-99.9), 85.7% (95% CI, 42.1-99.6) in nasopharyngeal swab, saliva, and sputum samples, respectively. These results indicate that the nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error. Nasopharyngeal swab, sputum and saliva samples were collected from 9 patients who 69 were admitted to our hospital after a diagnosis of COVID-19. Saliva as a 187 non-invasive specimen for detection of SARS-CoV-2 Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva Detection of noroviruses in fecal specimens by direct RT-PCR 195 without RNA purification cache = ./cache/cord-311333-shvtfxog.txt txt = ./txt/cord-311333-shvtfxog.txt === reduce.pl bib === id = cord-312414-g5px0b65 author = Takagi, Akira title = An immunodominance hierarchy exists in CD8+ T cell responses to HLA-A*02:01-restricted epitopes identified from the non-structural polyprotein 1a of SARS-CoV-2 date = 2020-09-19 pages = extension = .txt mime = text/plain words = 4076 sentences = 230 flesch = 61 summary = As shown in Fig. 2 , the intracellular cytokine staining (ICS) assay showed that 173 significant numbers of IFN--producing CD8+ T cells were elicited in mice immunized 174 with 18 liposomal peptides including pp1a-38, -52, -84, -103, -445, -597, -641, -1675, 175 -2785, -2884, -3083, -3403, -3467, -3583, -3662, -3710, -3732, and -3886, revealing that 176 these 18 peptides are HLA-A*02:01-restricted CTL epitopes derived from SARS-CoV-2 177 pp1a. However, any of 18 185 epitopes are not found in the amino acid sequence of either MERS-CoV or the four 186 common cold human coronaviruses involving HCoV-OC43, In the 18 positive peptides, 10 peptides including pp1a-38, -84, -641, -1675, -2884, 189 -3467, -3583, -3662, -3710, and -3732 were selected for the following analyses because 190 of the high ratios of IFN- + cells in CD8 + T cells (Fig. 2) . At first glance, the graphs of CD107a ( Taken together, 10 peptides differed significantly in their ability to induce 226 SARS-CoV-2 pp1a-specific CTLs when mice were immunized with the mixture of 10 227 peptides in liposomes. cache = ./cache/cord-312414-g5px0b65.txt txt = ./txt/cord-312414-g5px0b65.txt === reduce.pl bib === id = cord-312999-3erodkv9 author = Hassan, Sk. Sarif title = Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2 date = 2020-09-06 pages = extension = .txt mime = text/plain words = 3920 sentences = 236 flesch = 53 summary = SARS-CoV-2 has been reported to be uniquely characterized by the accessory protein ORF10, which contains eleven cytotoxic T lymphocyte (CTL) epitopes of nine amino acids length each, across various human leukocyte antigen (HLA) subtypes. In this study, all missense mutations found in sequence databases were examined across twnety-two unique SARS-CoV-2 ORF10 variants that could possibly alter viral pathogenicity. The high degree of physicochemical and structural similarity of ORF10 proteins of SARS-CoV-2 and Pangolin-CoV open questions about the architecture of SARS-CoV-2 due to the disagreement of these two ORF10 proteins over their sub-structure (loop/coil region), solubility, antigenicity and change from the strand to coil at amino acid position 26, where tyrosine is present. Based on the mutations, conserved and non-conserved residues in ORF10 proteins are identified and marked in different colors in (Figure There are altogether 22 distinct missense mutations which were examined across 22 unique ORF10 variants of SARS-CoV-2. cache = ./cache/cord-312999-3erodkv9.txt txt = ./txt/cord-312999-3erodkv9.txt === reduce.pl bib === id = cord-314445-4cb4a9r5 author = McNamara, Ryan P. title = High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date = 2020-06-19 pages = extension = .txt mime = text/plain words = 1960 sentences = 131 flesch = 53 summary = This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. The current COVID-19 pandemic is an urgent public health emergency with over 112,000 deaths in the United States (U.S.) alone. At a CP ≥35 most positive samples still yielded reads that mapped to the target genome 227 and thus allowed detection of SARS-CoV-2 sequences; however, the results were less consistent, 228 and coverage was more variable. In sum, this study generated exhaustive SNV information representing the introduction and 325 spread of SARS-CoV-2 across a suburban low-density area in the Southern U.S. All samples were 326 from symptomatic cases and the majority of genomes clustered with variants that predominate the 327 outbreak in the U.S., rather than Europe or China. cache = ./cache/cord-314445-4cb4a9r5.txt txt = ./txt/cord-314445-4cb4a9r5.txt === reduce.pl bib === id = cord-314321-klb8oe9q author = Chen, Serena H. title = Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date = 2020-04-18 pages = extension = .txt mime = text/plain words = 3168 sentences = 174 flesch = 52 summary = Recent experimental structures of the SARS-CoV-2 S protein receptor binding domain (RBD) in complex with ACE2 provide detailed interface information [4] , [6] ; targeting this interface represents an active area of research for therapeutic development [11] . By first comparing the S protein protomer structure of SARS-CoV-2 to those from previous human coronaviruses, we identified distinct clusters for each virus in the 3-D latent space, where representative structures from these clusters highlight their differences in domain flexibility. To further understand the molecular structures of different human coronavirus S proteins and the oligomeric state of SARS-CoV-2 S protein, we deployed a custom-built deep learning architecture, a convolutional variational autoencoder (CVAE), to encode the high dimensional protein structures from the MD simulations into lower dimensional latent spaces. The size of each resulting matrix was also 191 ⇥ 191, and we merged a total of 10,000 distance matrices of the protomer and trimer of SARS-CoV-2 S protein. cache = ./cache/cord-314321-klb8oe9q.txt txt = ./txt/cord-314321-klb8oe9q.txt === reduce.pl bib === id = cord-315702-pn8247j2 author = Sahakijpijarn, Sawittree title = Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing date = 2020-09-22 pages = extension = .txt mime = text/plain words = 2300 sentences = 139 flesch = 48 summary = Remdesivir exhibits in vitro activity against SARS-CoV-2 and was granted approval for Emergency Use. To maximize delivery to the lungs, we formulated remdesivir as a dry powder for inhalation using thin film freezing (TFF). In conclusion, TFF technology produces high potency remdesivir dry powder formulations for inhalation suitable to treat patients with COVID-19 on an outpatient basis and earlier in the disease course where effective antiviral therapy can reduce related morbidity and mortality. Although several techniques have been used to prepare inhalable powders, including 116 mechanical milling and spray drying, the advantages of thin film freezing (TFF) over other techniques 5 of 39 rely on the ability to produce aerosolizable particles composed of brittle matrix, nanostructured 118 aggregates. This shows that the 530 TFF technology can be used to minimize the need of excipient(s) in the formulation, thus maximizing 531 the amount of remdesivir being delivered to the lungs by dry powder inhalation. cache = ./cache/cord-315702-pn8247j2.txt txt = ./txt/cord-315702-pn8247j2.txt === reduce.pl bib === id = cord-313805-6mnclfeg author = Suzuki, Yuichiro J. title = SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells date = 2020-10-12 pages = extension = .txt mime = text/plain words = 2299 sentences = 128 flesch = 56 summary = Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. The treatment of human pulmonary artery smooth muscle cells or human pulmonary artery endothelial cells with recombinant SARS-CoV-2 spike protein S1 subunit (Val16 – Gln690) at 10 ng/ml (0.13 nM) caused an activation of MEK phosphorylation. Our results showing that SARS-CoV-2 spike protein is capable of activating the MEK/ERK pathway in pulmonary artery smooth muscle and endothelial cells suggest that cell growth signaling may be triggered in the pulmonary vascular walls in response to SARS-CoV-2. The major finding of this study is that the SARS-CoV-2 spike protein without the rest of the virus can elicit cell signaling, specifically the activation of the MEK/ERK pathway, in human host lung vascular smooth muscle and endothelial cells. cache = ./cache/cord-313805-6mnclfeg.txt txt = ./txt/cord-313805-6mnclfeg.txt === reduce.pl bib === id = cord-313795-jr3n3uo9 author = McAuley, Julie L. title = Liquid chalk is an antiseptic against SARS-CoV-2 and influenza A respiratory viruses date = 2020-11-02 pages = extension = .txt mime = text/plain words = 1411 sentences = 85 flesch = 56 summary = We investigated whether liquid chalk is an antiseptic against highly pathogenic human viruses including, SARS-CoV-2, influenza virus and noroviruses. We observed that addition of chalk before or after virus contact lead to a significant reduction on recovery of infectious SARS-CoV-2 and influenza but had little impact on norovirus. To further our study, we also tested the antiviral effect of Liquid Chalk against another 155 highly infectious and pathogenic respiratory viral pathogen IAV. 157 As can be observed in Figure 2 , all four Liquid Chalk products were effective in restricting the 158 recovery of IAV compared to SARS-CoV-2. transmission of SARS-CoV-2 (the 52 causative agent of the COVID-19 pandemic), influenza A virus (H1N1) (IAV) and norovirus, 53 using the surrogate model of mouse norovirus As a comparator, we also investigated the ability of Liquid Chalk to inactivate another 178 highly infectious viral pathogen, norovirus. cache = ./cache/cord-313795-jr3n3uo9.txt txt = ./txt/cord-313795-jr3n3uo9.txt === reduce.pl bib === id = cord-317523-idji1l0a author = Xu, Huanzhou title = SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway date = 2020-10-27 pages = extension = .txt mime = text/plain words = 1192 sentences = 59 flesch = 42 summary = With the selective NLRP3 inhibitor MCC950 able to block ORF3a-mediated inflammasome activation and key ORF3a residues needed for virus release and inflammasome activation conserved in SARS-CoV-2 isolates across continents, ORF3a and NLRP3 present prime targets for intervention. In a pared-down system, we investigate the influence of ORF3a, an essential SARS-CoV-2 protein, on the inflammatory machinery and find that it activates NLRP3, the most prominent inflammasome by causing potassium loss across the cell membrane. To assess if ORF3a also 135 mediates activation of other prominent inflammasomes including NLRP1 and NLRC4, we 136 depleted each of these molecules but were unable to block cleavage of pro-caspase 1 (Fig.2G) , 137 indicating that ORF3a predominantly activates the NLRP3 inflammasome. In summary, an essential viroporin required for release of SARS-CoV-2 from infected cells is also 178 able to prime and activate the NLRP3 inflammasome, the machinery responsible for much of the cache = ./cache/cord-317523-idji1l0a.txt txt = ./txt/cord-317523-idji1l0a.txt === reduce.pl bib === id = cord-314329-rzda8x62 author = Wells, Stephen A. title = Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure date = 2020-03-12 pages = extension = .txt mime = text/plain words = 4108 sentences = 208 flesch = 50 summary = A judicious combination of simplified methodologiesrigidity analysis, elastic network modelling, and geometric simulation of flexible motioncan work together to extract valuable information on the large-amplitude, low-frequency motions of a protein structure, at a fraction of the computational cost (in resources and time) of molecular dynamics (MD) approaches [3] . The simulations reported here suggest that the protease structure is capable of substantial flexible motions which alter domain orientations, open and close clefts, and affect the geometry of an inhibitor-binding site. The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. cache = ./cache/cord-314329-rzda8x62.txt txt = ./txt/cord-314329-rzda8x62.txt === reduce.pl bib === id = cord-313215-diqfmitr author = Luo, Lei title = Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases date = 2020-07-09 pages = extension = .txt mime = text/plain words = 1593 sentences = 90 flesch = 52 summary = title: Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases Background Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. To address this question, in this study, we sampled total of 641 surfaces 63 environmental and air specimens among 39 cases in Guangzhou, China, to explore the 64 surrounding environmental surfaces and air contamination by SARS-CoV-2 in non-65 health care settings. A total of 641 157 environmental surfaces and air specimens were collected among 39 COVID-19 cases, 158 and 20 specimens (20/641, 3.1%) were positive by RT-PCR testing from 9 COVID-19 159 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic 160 cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases 161 ( of SARS-CoV-2 (Table 2) . cache = ./cache/cord-313215-diqfmitr.txt txt = ./txt/cord-313215-diqfmitr.txt === reduce.pl bib === id = cord-313505-2lr4xara author = Resende, Paola Cristina title = Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date = 2020-06-18 pages = extension = .txt mime = text/plain words = 1145 sentences = 99 flesch = 55 summary = title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. Introduction 59 COVID-19, the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 60 (SARS-CoV-2), is leading to high rates of acute respiratory syndrome, hospitalization, and death 61 genomes (> 10% of ambiguous positions), we obtained a final dataset of 7,674 sequences. The prevalence of the sub-clade 211 B.1.1 in our sample (92%) was much higher than that observed in other Brazilian sequences 212 available in GISAID (36%) (Fig. 1C) phylogenetic tree, consistent with the hypothesis of multiple independent introductions (Fig. 2) (Fig. 2) . Revealing COVID-19 Transmission by SARS-CoV-2 Genome 410 Sequencing and Agent Based Modelling. cache = ./cache/cord-313505-2lr4xara.txt txt = ./txt/cord-313505-2lr4xara.txt === reduce.pl bib === id = cord-320490-3jmo35jc author = Ismail, Saba title = Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine date = 2020-04-12 pages = extension = .txt mime = text/plain words = 6688 sentences = 412 flesch = 52 summary = In this study, we characterized the SARS-CoV-2 spike glycoprotein by immune-informatics techniques to put forward potential B and T cell epitopes, followed by the use of epitopes in construction of a multi-epitope peptide vaccine construct (MEPVC). Stable conformation of the MEPVC with a representative innate immune TLR3 receptor was observed involving strong hydrophobic and hydrophilic chemical interactions, along with enhanced contribution from salt-bridges towards inter-molecular stability. The study presented, herein, is an attempt to get insights about antigenic determinants of SARS-CoV-2 spike glycoprotein and highlight all antigenic epitopes [31] of the spike that can be used specifically for the design of a multi-epitope peptide vaccine construct (MEPVC) [32] to counter COVID-19 infections. The epitopes predicted by immunoinformatics techniques were fused together as well as to β-defensin adjuvant [33, 34] to boost the antibody production and longThe MEPVC affinity for an appropriate immune receptor as an agonist was checked in the step of molecular docking [60] . cache = ./cache/cord-320490-3jmo35jc.txt txt = ./txt/cord-320490-3jmo35jc.txt === reduce.pl bib === id = cord-320054-wqpr8v3p author = Yuan, Xianlin title = The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes date = 2020-08-24 pages = extension = .txt mime = text/plain words = 2588 sentences = 156 flesch = 58 summary = In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. To explore these questions, here we report 94 to used these immuno-bioinformatic tools from the IEDB and related resources to 95 predict the B cell epitopes of S protein from the prototype and mutated strains of 96 SARS-CoV-2 and compare the changes of the likely epitope sites from dominant and 97 rare mutations of S protein. The major variation sequences were available 409 from The Global Initiative for Sharing All Influenza Data (GISAID) [26] and GenBank 446 We used the sequence from early onset SARS-CoV-2 as the wildtype or prototype and 447 the recent variant virus as mutation strains to predict the B-cell epitopes of S protein. cache = ./cache/cord-320054-wqpr8v3p.txt txt = ./txt/cord-320054-wqpr8v3p.txt === reduce.pl bib === id = cord-317628-1inxq7t5 author = Cuccarese, Michael F. title = Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date = 2020-08-14 pages = extension = .txt mime = text/plain words = 9573 sentences = 487 flesch = 43 summary = We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). cache = ./cache/cord-317628-1inxq7t5.txt txt = ./txt/cord-317628-1inxq7t5.txt === reduce.pl bib === id = cord-315982-iuez41zj author = Achdout, Hagit title = COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning date = 2020-10-30 pages = extension = .txt mime = text/plain words = 4103 sentences = 223 flesch = 54 summary = title: COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning Herein we provide a living summary of the data generated during the COVID Moonshot project focused on the development of SARS-CoV-2 main protease (Mpro) inhibitors. The COVID Moonshot project has focused on progressing early fragment-screening results into potent compounds with activity against both the main protease and the virus. The rationales for each design include docking-based approaches, by-eye structure-based designs, machine learning approaches, crawling of the past literature on SARS and MERS compounds, and other general medicinal-chemistry insights that can be visualised at https://postera.ai/covid. At 24 h post-seeding, cell culture medium was discarded, cells were washed twice with PBS and infected with SARS-CoV-2 at an MOI of 0.01 in the presence of six concentrations of the inhibitors (25 M -0.06 M). cache = ./cache/cord-315982-iuez41zj.txt txt = ./txt/cord-315982-iuez41zj.txt === reduce.pl bib === id = cord-319447-xanewi59 author = Sun, Jiya title = Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection date = 2020-05-01 pages = extension = .txt mime = text/plain words = 3250 sentences = 163 flesch = 52 summary = To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. In this study, we used the SARS-CoV-2 strain isolated from patients [11] to infect in vitro Calu-3 cells, and performed RNA sequencing to determine the time-series transcriptome profiling data of the host. Next, to gain possible explanations for the distinct patterns in host antiviral capacity and cytokine production during SARS-CoV-2 infection, dynamic expression of four types of key genes were evaluated, including virus receptors for cell entry, pathogen recognition receptors (PRRs) for an innate immune startup, regulator genes for induction of antiviral-related genes and interferon production (Figure 4) . cache = ./cache/cord-319447-xanewi59.txt txt = ./txt/cord-319447-xanewi59.txt === reduce.pl bib === id = cord-321050-yabt72jf author = Tuttle, Kathryn D. title = JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date = 2020-04-09 pages = extension = .txt mime = text/plain words = 4121 sentences = 208 flesch = 46 summary = Increasing evidence supports the notion that mortality during infections with SARS-CoV-2, which causes coronavirus disease of 2019 , is driven by the exacerbated immune response to the virus, leading to a cascade of events involving a cytokine storm and acute respiratory distress syndrome (ARDS), often accompanied by myocardial damage and multiple organ failure (5, 6) . Overall, these results have potential far-reaching significance for the treatment of COVID-19, justifying a deeper study of JAK inhibitors as a therapeutic strategy to attenuate the cytokine storm and downstream organ failure in this condition, while also indicating that individuals with DS should be considered a high-risk population during the COVID-19 pandemic. This analysis revealed that Dp16 mice have increased liver pathology even before P(I:C) treatment, as demonstrated by significantly higher levels of cell injury, inflammation, and reactive changes relative to their WT littermates (Figure 4B,C) . cache = ./cache/cord-321050-yabt72jf.txt txt = ./txt/cord-321050-yabt72jf.txt === reduce.pl bib === id = cord-320417-01l27d99 author = Wang, Hai-Long title = The emergence of inter-clade hybrid SARS-CoV-2 lineages revealed by 2D nucleotide variation mapping date = 2020-10-14 pages = extension = .txt mime = text/plain words = 5013 sentences = 257 flesch = 52 summary = I proposed a novel illustrating method using a 2D map to display populations of co-occurring nucleotide variants for intraand inter-viral clades. Using this method, I revealed the emergence of inter-clade hybrid SARS-CoV-2 lineages that are potentially caused by homologous genetic recombination. SARS-CoV-2 is an RNA virus with limited genome length, but its high mutation rate and homologous genetic recombination nonetheless gave rise to exponentially increased variants. This is why all previously reported recombination events of SARS-Cov-2 have relied on clade-defining SNPs. The 2D co-occurring variant mapping is a simple way to display inter-clade hybrid lineages, and it can be used to directly compare distributions of populations for intra-and inter-clade from different geographic locations or the same location but at a different time point. I downloaded ~18,000 SARS-CoV-2 genome sequences from NCBI (on September 2 nd ) and used the same criterion as before to search for inter-clade co-occurring SNP pairs (see method for details). cache = ./cache/cord-320417-01l27d99.txt txt = ./txt/cord-320417-01l27d99.txt === reduce.pl bib === id = cord-313910-bwe2f7xf author = Bojadzic, Damir title = Small-Molecule In Vitro Inhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 date = 2020-10-22 pages = extension = .txt mime = text/plain words = 7049 sentences = 346 flesch = 54 summary = Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel drug-like compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC50s of 0.2-3.0 μM); whereas, control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. We were able to set up a cell-free ELISA-type assay to quantify the binding of SARS-CoV-2 S protein (as well as its SARS-CoV analog) to their cognate receptors (human ACE2) and used this to screen our existing in-house compound library containing a large variety of organic dyes and a set of colorless analogs prepared as potential SMIs for costimulatory PPIs. These maintain the main molecular framework of dyes but lack the aromatic azo chromophores responsible for the color as they are replaced with amide linkers (58, 59). cache = ./cache/cord-313910-bwe2f7xf.txt txt = ./txt/cord-313910-bwe2f7xf.txt === reduce.pl bib === id = cord-315760-9g8901v6 author = Teng, Xufei title = Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades date = 2020-08-30 pages = extension = .txt mime = text/plain words = 3532 sentences = 182 flesch = 59 summary = Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code, to molecular mechanisms based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on replicase-transcriptase complex. Our analysis starts with primary sequence information and identity-based phylogeny based on 22,051 SARS-CoV-2 genome sequences and evaluation of sequence variation patterns as mutation spectrum and its 12 permutations among organized clades tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings include: (1) The most dominant mutation is C-to-U permutation whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity albeit assumed most slightly deleterious. We have further examined the compositional subtleties among the clades and clusters with 304 a focus on G+C and purine content variability as both contents appear drifting toward optima 305 in SARS-CoV-2 and its relatives ( Figure 5C and 5D). cache = ./cache/cord-315760-9g8901v6.txt txt = ./txt/cord-315760-9g8901v6.txt === reduce.pl bib === id = cord-318499-uihof6k6 author = Beddingfield, Brandon title = The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection date = 2020-06-16 pages = extension = .txt mime = text/plain words = 1550 sentences = 100 flesch = 54 summary = Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting ACE2 binding with the SARS-CoV-2 spike protein. This work focuses on the potential to inhibit SARS-CoV-2 entry through a hypothesized α5β1integrin-based mechanism, and indicates that inhibiting α5β1 integrin interaction with ACE2 and the spike protein using a novel molecule ATN-161 represents a promising approach to treat COVID-19. In order to assess disruption of binding of α5β1 to SARS-CoV-2 Spike protein, 96-well plates were coated as before, but incubation with ATN-161 was performed in conjunction with 1µg/mL spike (produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike Glycoprotein Receptor Binding Domain (RBD) from SARS-Related Coronavirus 2, Wuhan-Hu-1, Recombinant from HEK293 Cells, NR-52306) in the presence of 1mM MnCl2, followed by detection with an anti-spike antibody. Inhibition of SARS-CoV-2 spike protein binding to human ACE2 by ATN-161. cache = ./cache/cord-318499-uihof6k6.txt txt = ./txt/cord-318499-uihof6k6.txt === reduce.pl bib === id = cord-321155-dty18esg author = Zhang, Rongxin title = Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2 date = 2020-06-05 pages = extension = .txt mime = text/plain words = 4927 sentences = 331 flesch = 57 summary = We also found that the SUD-like sequence is retained in the SARS-CoV-2 genome, while some other coronaviruses that can infect humans are depleted. To get the potential G-quadruplexes in the SARS-CoV-2 genome, we took the strategy described as follows ( Fig. 2A) : (i) Predicting the PG4s with three software independently. To further characterize the potential canonical secondary structures competitive with Gquadruplexes, the landscape of thermodynamic stability of the SARS-CoV-2 genome was depicted by using ΔG°z-score [55] . The distributions of loop length between the SARS-CoV-2 PG4s and the human two-quartet Gquadruplexes did not show discrepancies (Fig. S1 , Wilcoxon test, p-value = 0.4552). Recent research revealed that the G-quadruplexes in human UTRs (Untranslated Regions) are under selective pressures [58] , and some coronaviruses on bats and pangolins are closely related to SARS-CoV-2. Thus, we started to explore whether the SARS-CoV-2 genome contains the protein-coding sequence similar to SUD and whether SARS-CoV-2 retains the ability to bind RNA G-quadruplexes. cache = ./cache/cord-321155-dty18esg.txt txt = ./txt/cord-321155-dty18esg.txt === reduce.pl bib === id = cord-317123-0tdfvlqd author = Tan, Xiaotian title = Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples date = 2020-04-21 pages = extension = .txt mime = text/plain words = 4154 sentences = 220 flesch = 52 summary = Here, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen – S protein in serum. We also characterized various humanized monoclonal IgG, and identified a candidate with a high binding affinity towards SARS-CoV-2 S1 protein that can serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. In this work, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, and sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen -S protein, both of which are spiked in serum, as a model system. For the anti-S1 IgG detection experiments (see Figure S2 (B) for the detailed protocol), various concentrations of monoclonal antibodies were prepared by diluting the stock solutions with 50 times diluted human serum (the serum was diluted with 1× reagent diluent, which correlates to 1% BSA). cache = ./cache/cord-317123-0tdfvlqd.txt txt = ./txt/cord-317123-0tdfvlqd.txt === reduce.pl bib === id = cord-323041-wf0hlhim author = Larsen, Mads Delbo title = Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19 date = 2020-05-18 pages = extension = .txt mime = text/plain words = 1413 sentences = 92 flesch = 56 summary = Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. Moreover, we have reported the lowered IgG-Fc fucosylation to be one of the factors 58 determining disease severity in pregnancy associated alloimmunizations, resulting in 59 excessive thrombocytopenia's and blood cell destruction when targeted by afucosylated 60 antibodies (11-13). 109 Analogous to the platelet and Red Blood cell alloantigens (10-12, 18), the response to these 110 enveloped viruses also showed significant afucosylation of the antigen-specific IgG (Fig.2B) , 111 while the afucosylation was absent against the non-enveloped virus Parvo B19 (Fig.2C ). Regulated glycosylation patterns of IgG during alloimmune 405 responses against human platelet antigens cache = ./cache/cord-323041-wf0hlhim.txt txt = ./txt/cord-323041-wf0hlhim.txt === reduce.pl bib === id = cord-321049-9ozn6il7 author = de Almeida, Paula Rodrigues title = SARS-CoV2 quantification using RT-dPCR: a faster and safer alternative to assist viral genomic copies assessment using RT-qPCR date = 2020-05-01 pages = extension = .txt mime = text/plain words = 1308 sentences = 73 flesch = 49 summary = title: SARS-CoV2 quantification using RT-dPCR: a faster and safer alternative to assist viral genomic copies assessment using RT-qPCR Narrower confidence intervals, indicating high quantification precision were obtained in 100 and 1000-fold serial dilution and RT-dPCR results were equivalent between different assays in the same dilution. Here, we present a fast, accurate and simple method of viral titration using QuantStudio 3D® microchip based RT-dPCR to titrate SARS-CoV2 genomic copies from controls to be used in RT-qPCR assays for diagnosis and research purposes. A dilution that results in approximately 200 to 2000 target copies in the final reaction usually presents better precision values. Results with precision values below 5% were selected to estimate quantity of SARS-CoV2 genomic copies based on RT-dPCR. RT-dPCR results of 10-fold serial dilution of SARS-CoV2 control using assays for three targets in the Nucleocapsid gene. These results indicate that these primer-probe assays are suitable for SARS-CoV2 quantification through RT-dPCR. cache = ./cache/cord-321049-9ozn6il7.txt txt = ./txt/cord-321049-9ozn6il7.txt === reduce.pl bib === id = cord-318478-fn0gcxbb author = Ziv, Omer title = The short- and long-range RNA-RNA Interactome of SARS-CoV-2 date = 2020-10-07 pages = extension = .txt mime = text/plain words = 5760 sentences = 343 flesch = 56 summary = Available models for the RNA structure of SARS-CoV-2 and related viruses are largely confined to short-distance base-pairing which result in local folding of important cis-acting elements (Andrews et al., 2020; Huston et al., 2020; Kelly et al., 2020; Lan et al., 2020; Manfredonia et al., 2020; Ryder, 2020; Sanders et al., 2020; Sun et al., 2020) . In addition to the canonical UTR structures, we provide here a direct in vivo evidence for genome cyclization in SARS-CoV-2, mediated by long-range base-pairing between the 5′ and 3′ UTRs ( Figures 5B and S4B ). The long-distance RNA structure map for SARS-CoV-2 provides a practical starting point to dissect the regulation of discontinuous transcription, as it identifies cis-acting elements that interact with each other to create genome topologies that favour the synthesis of the ensemble of sgmRNAs. RNA viruses evolve sophisticated mechanisms to enhance the functional capacity of their size-restricted genomes and to regulate the expression levels of their replicase components. cache = ./cache/cord-318478-fn0gcxbb.txt txt = ./txt/cord-318478-fn0gcxbb.txt === reduce.pl bib === id = cord-321027-64y43o0y author = Andreano, Emanuele title = Identification of neutralizing human monoclonal antibodies from Italian Covid-19 convalescent patients date = 2020-05-09 pages = extension = .txt mime = text/plain words = 2287 sentences = 114 flesch = 51 summary = The SARS-CoV-2 spike glycoprotein (S-protein) has a pivotal role in viral pathogenesis and it is 63 considered the main target to elicit potent neutralizing antibodies and the focus for the development 64 of therapeutic and prophylactic tools against this virus (3, 4) . Results shown in Table 1 and Figure 1 show that, among the seven donors 97 included in this study, six were able to produce high titers of SARS-CoV-2 S-protein specific 98 antibodies and in particular donors R-042, R-122 and R-188 showed the highest virus neutralizing 99 titers. In the case of SARS-CoV-2, where so far we do not have any effective therapeutic nor prophylactic 154 interventions, mAbs have the possibility to become one of the first drugs that can be used for 155 immediate therapy of any patient testing positive for the virus, and even to provide immediate 156 protection from infection in high risk populations. cache = ./cache/cord-321027-64y43o0y.txt txt = ./txt/cord-321027-64y43o0y.txt === reduce.pl bib === id = cord-322942-y4zd2oui author = Olagnier, David title = Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate date = 2020-07-17 pages = extension = .txt mime = text/plain words = 3756 sentences = 203 flesch = 50 summary = Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. Here we demonstrate that expression of NRF2-dependent genes is suppressed in biopsies from 104 COVID-19 patients and that treatment of cells with NRF2 agonists 4-OI and DMF induces a 105 strong anti-viral program that limits SARS-CoV2 replication. Interestingly, when 176 treating Calu3 cells with DMF, another known NRF2 inducer and a clinically approved drug in 177 the first-line-of treatment of multiple sclerosis, we could also observe an anti-viral effect toward 178 SARS-CoV2 replication similar in magnitude as what we had observed with 4-OI (Fig 2p-q) as 179 well as a reduced but significant effect when using Vero cells (Fig. 2r) . cache = ./cache/cord-322942-y4zd2oui.txt txt = ./txt/cord-322942-y4zd2oui.txt === reduce.pl bib === id = cord-319100-3gdawhfn author = Kirkland, P.D. title = The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2 and other viruses date = 2020-06-10 pages = extension = .txt mime = text/plain words = 4624 sentences = 204 flesch = 49 summary = authors: Kirkland, P.D.; Frost, M.J. title: The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2 and other viruses Also of concern are recommendations (3, 4) to include foetal bovine serum (fbs) as a source of protein to enhance the stabilising properties of VTMs. This report documents observations of the adverse impact of certain VTMs on real time reverse transcription PCR (qRT-PCR) assays for the detection of SARS-CoV-2 virus as well as on a Type A influenza virus and a herpesvirus and discuss the broader implications of the inclusion of foetal bovine serum as a protein supplement to VTMs. During the initial investigation, purified RNA from an Australian isolate (WMD DC1) of SARS-CoV-2 was supplied to the Elizabeth Macarthur Agriculture Institute (EMAI) by the Institute of Clinical Pathology and Medical Research (ICPMR), Westmead, New South Wales (NSW). cache = ./cache/cord-319100-3gdawhfn.txt txt = ./txt/cord-319100-3gdawhfn.txt === reduce.pl bib === id = cord-318253-vp22xd8p author = Parisi, Ortensia Ilaria title = “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers date = 2020-05-28 pages = extension = .txt mime = text/plain words = 1858 sentences = 96 flesch = 38 summary = Our idea is focused on the development of "monoclonal-type" plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. In this context, our idea is to develop "monoclonal-type" plastic antibodies based on Molecularly Imprinted Polymers (MIPs) for the selective recognition and binding of the RBD of the novel coronavirus SARS-CoV-2 in the aim to block the function of its spike protein (Figure 1.) . cache = ./cache/cord-318253-vp22xd8p.txt txt = ./txt/cord-318253-vp22xd8p.txt === reduce.pl bib === id = cord-323828-ug2duzw1 author = Ni, Dongchun title = Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein date = 2020-10-12 pages = extension = .txt mime = text/plain words = 3408 sentences = 234 flesch = 65 summary = Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. The clinical-grade soluble form of hACE2 has been reported to be a 74 potential novel therapeutic approach for reducing the infection of SARS-CoV-2 (Monteil et al., 2020) by preventing the viral Spike from interacting with other hACE2 present on human cells. The final 3D 115 reconstruction from 72'446 particles at 5.1Å overall resolution showed a density map corresponding to a single, 116 monomeric Spike protein in complex with hACE2 (Fig. 1a) . Figure 1 Cryo-EM maps of SARS-CoV-2 Spike-hACE2 complexes and fitted models. Cryo-EM structure of the SARS coronavirus spike glycoprotein in 352 complex with its host cell receptor ACE2 cache = ./cache/cord-323828-ug2duzw1.txt txt = ./txt/cord-323828-ug2duzw1.txt === reduce.pl bib === id = cord-323654-9nnjex9y author = Ramachandran, Ashwin title = Electric-field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2 date = 2020-05-22 pages = extension = .txt mime = text/plain words = 1549 sentences = 115 flesch = 62 summary = Unlike previous CRISPR diagnostic assays, we also use ITP for automated purification of target RNA from raw nasopharyngeal swab sample. We here combine this ITP purification with loop-mediated isothermal amplification, and the ITP-enhanced CRISPR assay to achieve detection of SARS-CoV-2 RNA (from raw sample to result) in 30 min for both contrived and clinical nasopharyngeal swab samples. We also demonstrated on-chip ITP extraction of total nucleic acids from raw clinical 175 positive and negative nasopharyngeal swab samples (Figs. We observed that ITP-extracted nucleic acids showed E gene amplification on positive qPCR-based detection approaches is provided in Table 1 . We propose here 520 the concept that such a system can integrate ITP-based nucleic acid extraction, 521 multiplexed isothermal amplification of target cDNA of N and E genes of SARS-CoV-2 522 and RNase P control, followed by ITP-CRISPR-based cDNA detection in three separate 523 channels using photodiodes. cache = ./cache/cord-323654-9nnjex9y.txt txt = ./txt/cord-323654-9nnjex9y.txt === reduce.pl bib === id = cord-318444-sgm24q1i author = Walter, Justin D. title = Sybodies targeting the SARS-CoV-2 receptor-binding domain date = 2020-05-16 pages = extension = .txt mime = text/plain words = 5902 sentences = 416 flesch = 49 summary = Two independently prepared RBD constructs were used for in vitro sybody selections, and resulting single clones that could bind the full spike ectodomain were sequenced, expressed, and purified. Six unique sybodies show favorable binding affinity to the SARS-CoV-2 spike, and five of these were also found to substantially attenuate the interaction between the viral RBD and human ACE2. While this purified pre-fusion spike (PFS) had not yet been available for binder selections and characterization by grating-coupled interferometry, it was used to conduct ELISAs in order to identify selected sybodies which recognize the RBD in the pre-fusion context (see below). Since virulence of SARS-CoV-2 is dependent on the ability of the viral RBD to bind to human ACE2 (hACE2), we sought to determine which of the 57 selected sybodies that were well-behaved upon purification could inhibit interaction between the isolated RBD and purified hACE2. cache = ./cache/cord-318444-sgm24q1i.txt txt = ./txt/cord-318444-sgm24q1i.txt === reduce.pl bib === id = cord-323685-gjocoa60 author = Tsai, Shang-Jui title = Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination date = 2020-11-06 pages = extension = .txt mime = text/plain words = 5332 sentences = 289 flesch = 49 summary = The resulting combinatorial vaccine, LSNME/SW1, was injected into thirteen weeks-old, male C57BL/6J mice, followed by interrogation of humoral and cellular immune responses to the SARS-CoV-2 nucleocapsid and spike proteins, as well as hematological and histological analysis to interrogate animals for possible adverse effects. Conclusion Taken together, these results validate the use of exosomes for delivering functional mRNAs into target cells in vitro and in vivo, and more specifically, establish that the LSNME/SW1 vaccine induced broad immunity to multiple SARS-CoV-2 proteins. These antigen-responsive CD4+ and CD8+ populations were present nearly two months after the final boost injection, indicating that LSNME/S W1 vaccination had elicited a sustained cellular immune response to both of these SARS-CoV-2 structural proteins. As for the future development of the LSNME/S W1 vaccine, we anticipate that follow-on studies in larger animal models at doses comparable to other mRNA vaccines will demonstrate a desirable combination of safety, balanced immune responses, and when challenged, protection against SARS-CoV-2 infection and/or disease. cache = ./cache/cord-323685-gjocoa60.txt txt = ./txt/cord-323685-gjocoa60.txt === reduce.pl bib === id = cord-321166-nvphu1fm author = Thomson, Emma C. title = The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date = 2020-11-05 pages = extension = .txt mime = text/plain words = 9813 sentences = 514 flesch = 55 summary = We find that the N439K mutation is associated with a similar clinical spectrum of disease and slightly higher viral loads in vivo compared with isolates with the wild-type N439 residue, and that it results in immune escape from polyclonal sera from a proportion of recovered individuals and a panel of neutralizing mAbs. N439K provides a sentinel example of immune escape, indicating that RBM variants must be evaluated when considering vaccines and the therapeutic or prophylactic use of mAbs. Long term control of the pandemic will require systematic monitoring of immune escape variants and selection of strategies that address the variants circulating in targeted populations. Fitness of this variant, N439K, was demonstrated by repeated emergence by convergent evolution, spread to multiple countries and significant representation in the SARS-CoV-2 sequence databases, the fact that the N439K RBD retains a high affinity interaction with the hACE2 receptor, efficient viral replication in cultured cells, and no disease attenuation in a large cohort of infected individuals. cache = ./cache/cord-321166-nvphu1fm.txt txt = ./txt/cord-321166-nvphu1fm.txt === reduce.pl bib === id = cord-325432-geb4esu5 author = Bukreyeva, Natalya title = The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro date = 2020-04-09 pages = extension = .txt mime = text/plain words = 1036 sentences = 65 flesch = 49 summary = Drugs with history of being tested in human patients or used for treatment of other conditions offer the most expedient option, and several such drugs are currently being tested for efficacy against SARS-CoV-2, including many broad-spectrum antivirals. One such antiviral, merimepodib (MMPD), has already being tested against hepatitis C in patients as well as against many emerging RNA viruses in cell culture, including Zika, Ebola, Lassa, Junin, and chikungunya viruses (1) . Early work suggests that IMPDH may directly interact with SARS-CoV-2 nsp13, perhaps indicating that drugs targeting IMPDH such as MMPD might have an impact on viral replication (5) . Our results show that MMPD can inhibit SARS-CoV-2 replication at low concentrations. Further work is needed to characterize the full mechanism behind MMPD inhibition of SARS-CoV-2 as well as its efficacy in animal models of corona virus infections. Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens cache = ./cache/cord-325432-geb4esu5.txt txt = ./txt/cord-325432-geb4esu5.txt === reduce.pl bib === id = cord-324251-wgtatr8v author = Joshi, Madhvi title = Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology date = 2020-07-13 pages = extension = .txt mime = text/plain words = 608 sentences = 46 flesch = 57 summary = title: Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology Latest edition to this pandemic list is COVID-19, caused by the novel coronavirus, SARS-CoV-2. Here, 361 SARS-CoV-2 genomes from across Gujarat have been sequenced and analyzed in order to understand its phylogenetic distribution and variants against global and national sequences. Further, variants were analyzed from diseased and recovered patients from Gujarat and the World to understand its role in pathogenesis. From missense mutations, found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in nucleocapsid (N) gene was found to be significantly associated with mortality in patients. SARS-CoV-2 genomes from Gujarat are forming distinct cluster under GH clade of GISAID. Positive selection of ORF3a and 477 ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic Full-genome sequences of the first two SARS-CoV-2 485 viruses from India cache = ./cache/cord-324251-wgtatr8v.txt txt = ./txt/cord-324251-wgtatr8v.txt === reduce.pl bib === id = cord-322654-6nccarjn author = Luzes, Rafael title = Angiotensin-(3–4) modulates angiotensin converting enzyme 2 (ACE2) downregulation in proximal tubule cells due to overweight and undernutrition: implications regarding the severity of renal lesions in Covid-19 infection date = 2020-06-29 pages = extension = .txt mime = text/plain words = 1447 sentences = 89 flesch = 52 summary = title: Angiotensin-(3–4) modulates angiotensin converting enzyme 2 (ACE2) downregulation in proximal tubule cells due to overweight and undernutrition: implications regarding the severity of renal lesions in Covid-19 infection Since the renin-angiotensin-aldosterone system (RAAS) has been implicated in the progress of kidney failure during Covid-19, we also investigated the influence of Angiotensin-(3–4) (Ang-(3–4)) the shortest angiotensin-derived peptide, which is considered the physiological antagonist of several angiotensin II effects. That Ang-(3-4)-mediated upregulation of renal ACE2 126 occurred in overweight rats, but not in the CTR group, is indicative that a "pro-127 hypertensive tissular microenvironment" (high Ang II) develops in animals fed with a 128 diet rich in lipids, causing downregulation of ACE2 (Figure 2A The influence of chronic undernutrition on renal ACE2 levels present some 132 similarity, but also a huge difference, compared with overweight rats (Figure 3) . cache = ./cache/cord-322654-6nccarjn.txt txt = ./txt/cord-322654-6nccarjn.txt === reduce.pl bib === id = cord-321369-xzu2faol author = Andreano, Emanuele title = Extremely potent human monoclonal antibodies from convalescent Covid-19 patients date = 2020-10-07 pages = extension = .txt mime = text/plain words = 3685 sentences = 192 flesch = 52 summary = By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2. As for the authentic virus neutralization assay, supernatants containing naturally produced IgG or IgA were tested for their ability to protect the layer of Vero E6 cells from the cytopathic effect triggered by SARS-CoV-2 infection (Fig. S2) . This work describes a systematic screening of memory B cells from convalescent people to identify extremely potent human monoclonal antibodies against the spike protein of the SARS-CoV-2 virus, to be used for prevention and therapy of Covid-19. cache = ./cache/cord-321369-xzu2faol.txt txt = ./txt/cord-321369-xzu2faol.txt === reduce.pl bib === id = cord-322955-7dw32xby author = Kathwate, Gunderao H title = In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date = 2020-06-12 pages = extension = .txt mime = text/plain words = 5729 sentences = 392 flesch = 47 summary = title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Those properties are calculated by different methods at IEDB server (http://tools.iedb.org/bcell/ )like Kolaskar-Tongaonkar antigenicity scale provide physiology of the amino acid residues(45), Emini Surface accessible score for accessible surface of the epitope(46), Secondary structure of epitopes also has role in antigenicity. High scored and common peptides predicted by various tools were selected for deriving sequence of potential vaccine candidate. We designed a multi-epitopes vaccine construct from S-protein of SARS-CoV2. From various epitopes predicted by the online server based on common sequence and high score three TCR and two BCR epitopes were selected as part of COVID19 vaccine. This vaccine codes epitopes form S protein of SARS-CoV2 virus for T and B cell receptors. cache = ./cache/cord-322955-7dw32xby.txt txt = ./txt/cord-322955-7dw32xby.txt === reduce.pl bib === id = cord-321427-bwcpd6im author = Yee, Min title = Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice date = 2020-07-22 pages = extension = .txt mime = text/plain words = 2154 sentences = 114 flesch = 58 summary = Instead, we made the surprising discovery that expression of Ace2 and Tmprss2 mRNA increases as mice age and is accelerated by exposing mice to neonatal hyperoxia. Our finding that early life insults such as hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in the respiratory epithelium helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities. When quantified, neonatal hyperoxia increased the number of alveolar cells expressing ACE2 by 148 approximately 50% at 2, 6 and 12 months of age (Figure 4b) . The levels of Tmprss2 mRNA and protein were examined in the lungs of 2-, 12-and 18-month-old mice that were exposed to neonatal hyperoxia and room air from PND0-4 by qRT-PCR 168 and western blotting. As observed for Ace2 expression, 173 exposure to ≥ 60% oxygen from PND4-0 was required to significantly increase the levels of Tmprss2 174 mRNA in the lungs of mice at 2 months of age (Figure 6c ). cache = ./cache/cord-321427-bwcpd6im.txt txt = ./txt/cord-321427-bwcpd6im.txt === reduce.pl bib === id = cord-322885-ob5euspo author = Durdagi, Serdar title = Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing date = 2020-09-09 pages = extension = .txt mime = text/plain words = 10818 sentences = 656 flesch = 54 summary = One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19. Radiation-damage-free SFX method which enables obtaining the novel high-resolution ambient-temperature structures of the binding pocket of Mpro provides an unprecedented opportunity for identification of highly effective inhibitors for drug repurposing by using a hybrid approach that combines structural and in silico methods. We determined two radiation-damage-free SFX crystal structures of SARS-CoV-2 Mpro in two crystal forms at 1.9 Å and 2.1 Å resolutions with the following PDB IDs: 7CWB and 7CWC, respectively (Fig. 1A, B) (Supplementary Table 1&2 The diffraction data collected remotely at the MFX instrument of the LCLS at SLAC National Laboratory, Menlo Park, CA (Sierra et al., They reveal novel active site residue conformations and dynamics at atomic level, revealing several differences compared to the prior ambient-temperature structure of SARS-CoV-2 Mpro that was obtained at a home X-ray source (Fig. 1A, B ). cache = ./cache/cord-322885-ob5euspo.txt txt = ./txt/cord-322885-ob5euspo.txt === reduce.pl bib === id = cord-324892-mg2dziuw author = Carneiro, João title = CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2 date = 2020-06-12 pages = extension = .txt mime = text/plain words = 901 sentences = 76 flesch = 48 summary = The first SARS-CoV-2 genomic sequences already showed novel mutations, which may affect the efficiency of available screening tests leading to false-negative diagnosis or inefficient therapeutics. Here we describe the CoV2ID (http://covid.portugene.com/), a free database built to facilitate the evaluation of molecular methods for detection of SARS-CoV-2 and treatment of COVID-19. The database evaluates the available oligonucleotide sequences (PCR primers, RT-qPCR probes, etc.) considering the genetic diversity of the virus. Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Rapid and visual detection of 2019 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal amplification assay Development of a Novel, Genome Subtraction-Derived, SARS-CoV-2-Specific COVID-19-nsp2 Real-Time RT-PCR Assay and Its Evaluation Using Clinical Specimens cache = ./cache/cord-324892-mg2dziuw.txt txt = ./txt/cord-324892-mg2dziuw.txt === reduce.pl bib === id = cord-324480-7u5lh4jx author = Sharma, A. title = Structural stability of SARS-CoV-2 degrades with temperature date = 2020-10-14 pages = extension = .txt mime = text/plain words = 1541 sentences = 88 flesch = 51 summary = Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. However an understanding of how SARS-CoV-2 survives different environmental conditions is still incomplete and mechanisms of virus particle degradation are poorly mapped out. A key challenge in studying SARS-CoV-2 is the extreme level of threat associated with the live virus and the resultant need for high safety standards for such work. Here we used this technology to study the stability of the viral envelope and associated proteins (M, E, and S) under different environmental conditions. Environmental stability of SARS-CoV-2 on different types of surfaces under indoor and seasonal climate conditions cache = ./cache/cord-324480-7u5lh4jx.txt txt = ./txt/cord-324480-7u5lh4jx.txt === reduce.pl bib === id = cord-323908-8dgngwmw author = He, Zhesheng title = Molecules inhibit the enzyme activity of 3-chymotrypsin-like cysteine protease of SARS-CoV-2 virus: the experimental and theory studies date = 2020-05-31 pages = extension = .txt mime = text/plain words = 881 sentences = 61 flesch = 59 summary = title: Molecules inhibit the enzyme activity of 3-chymotrypsin-like cysteine protease of SARS-CoV-2 virus: the experimental and theory studies Herein, we report that the clinical approved auranofin could perfectly inhibit the activity of 3-chymotrypsin-like cysteine protease (Mpro or 3CLpro) of SARS-CoV-2. As Au(I) ion is active metabolism specie derived from gold compounds or gold clusters in vivo, further computational studies revealed Au ion could tightly bind thiol group of Cys145 residue of 3CLpro thus inhibit enzyme activity. Also, phenyl isothiocyanate and Vitamin K3 may interact with thiol group of Cys145 via Michael addition reaction, molecular dynamic (MD) theory studied are applied to confirmed these small molecules are stable in the pocket and inhibit Mpro activity. These compounds could serve as potential anti-SARS-CoV-2 lead molecules for further drug studies to combat COVID-19. The interactions between the gold atom with the binding pockets of proteins were studied by density functional theory (DFT) calculations. cache = ./cache/cord-323908-8dgngwmw.txt txt = ./txt/cord-323908-8dgngwmw.txt === reduce.pl bib === id = cord-323839-a4oejky0 author = Sasaki, Michihito title = SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells date = 2020-08-28 pages = extension = .txt mime = text/plain words = 2100 sentences = 128 flesch = 63 summary = These results indicated that S gene mutants are resistant to the 1 5 9 treatment with TMPRRSS2 inhibitors, but are sensitive to antivirals that target post entry In an effort to understand the selection mechanisms underlying the generation of these 1 6 4 mutant variants, we estimated the frequency of S gene mutants in virus population of 1 6 5 SARS-CoV-2 that had undergone serial passage in cultured cells. In contrast, nucleotide sequence 1 7 2 deletions around the S1/S2 cleavage site corresponding to del1 and del2 mutants were 1 7 3 observed in all three biological replicates of SARS-CoV-2 populations passaged in Vero 1 7 4 cells (Fig. 5a) . Moreover, we must be very objective when interpreting the results 2 3 0 from studies using Vero-passaged virus, especially those focused on S protein cleavage, Cells were infected with either WT or S mutants of SARS-CoV-2 at an MOI of 1. cache = ./cache/cord-323839-a4oejky0.txt txt = ./txt/cord-323839-a4oejky0.txt === reduce.pl bib === id = cord-320165-1b6sycgv author = Guo, Qirui title = Small molecules inhibit SARS-COV-2 induced aberrant inflammation and viral replication in mice by targeting S100A8/A9-TLR4 axis date = 2020-09-09 pages = extension = .txt mime = text/plain words = 6762 sentences = 425 flesch = 54 summary = S100A8/A9 specific inhibitor, Paquinimod, significantly reduced the number of neutrophils activated by the coronavirus, inhibited viral replication and rescued lung damage a result of SARS-CoV-2 infection. The whole genome wide RNA-seq analysis of the lungs from infected rhesus macaques showed that a number of transcripts were induced or inhibited at day 3 and day 5 after SARS-CoV-2 infection (Supplementary Figure 1A) . Similar to the data from rhesus macaque experiments, compared to other alarmins, S100A8 was robustly induced by SARS-CoV-2 but not by IAV infection in mice ( Figure 2E ). The expression of these B cell related genes was rescued or induced by Paquinimod during MHV infection, which was confirmed by qRT-PCR analysis ( Figure 3M ). Moreover, both Paquinimod and Resatorvid suppressed the activation of coronavirus related neutrophils in lung during SARS-CoV-2 infection ( Figure 4D ). cache = ./cache/cord-320165-1b6sycgv.txt txt = ./txt/cord-320165-1b6sycgv.txt === reduce.pl bib === id = cord-325124-0hxan9rw author = Li, Chenyu title = Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing date = 2020-05-18 pages = extension = .txt mime = text/plain words = 6119 sentences = 364 flesch = 53 summary = However, it has been reported that only 47-59% of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites. With the goal of improving sensitivity and accommodating various application settings, we developed a multiplex-PCR-based method comprised of 343 pairs of specific primers, and demonstrated its efficiency to detect SARS-CoV-2 at low copy numbers. We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purified from 13 COVID-19 positive specimens, and detected mutations through next generation sequencing. Finally, we developed a multiplex-PCR-based metagenomic method in parallel, that required modest sequencing depth for uncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates. To overcome this constraint, we developed a multiplex-PCR-based metagenomic method that achieved >96% coverage of the S and N genes of SARS-CoV-2 in the contest of human gDNA, while only required ~0.6M of total reads per library. cache = ./cache/cord-325124-0hxan9rw.txt txt = ./txt/cord-325124-0hxan9rw.txt === reduce.pl bib === id = cord-324888-oak27okj author = Leng, Ling title = Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis date = 2020-04-18 pages = extension = .txt mime = text/plain words = 2814 sentences = 155 flesch = 46 summary = title: Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. Therefore, we wonder whether there are some key local microenvironment proteins specifically expressed on the surface of airway EpC that makes the virus prefer airway EpCs. In some cases, additional cell surface molecules or co-receptors are required for sufficient viral entry into host cells. We used the human protein atlas (HPA) database [16] to extract the protein expression level of 65 receptors involved in "virus receptor activity" (GO:0001618) of EpCs and epithelial or epithelial-derived cells from 14 organs (16 cell types) ( Figure 1A and Supplementary Materials and Methods). cache = ./cache/cord-324888-oak27okj.txt txt = ./txt/cord-324888-oak27okj.txt === reduce.pl bib === id = cord-326282-uxn64olw author = Lu, Maolin title = Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles date = 2020-09-13 pages = extension = .txt mime = text/plain words = 3264 sentences = 207 flesch = 55 summary = To measure conformational dynamics of the SARS-CoV-2 S trimer on the surface of virus particles, we established two types of particles, lentiviral pseudoparticles carrying S, as well as coronaviruslike particles generated by expression of S, membrane (M), envelope (E) and nucleocapsid (N) 15 protein (S-MEN)(24, 25) (Fig. 1, A and B ). Analyses of smFRET data from ligand-free S protein on lentiviral particles revealed that the SARS-CoV-2 S protein is dynamic, sampling at least four distinct conformational states To identify the receptor-bound conformation of the SARS-CoV-2 S protein by smFRET, we measured the conformational consequences of soluble, monomeric hACE2 binding. Addition of 5 the monomeric hACE2 receptor to surface-immobilized virus particles lead to increased occupancy of the low-(~0.1) FRET S protein conformation (Fig. 2E) , which was observed at both the single-molecule and population level (Fig. 2F ). Relative state-occupancy and fitting parameters in each of four FRET-defined conformational states of SARS-CoV-2 spike protein on the surface of virus particles. cache = ./cache/cord-326282-uxn64olw.txt txt = ./txt/cord-326282-uxn64olw.txt === reduce.pl bib === id = cord-327520-qj7coqfr author = Wei, Yulong title = Coronavirus genomes carry the signatures of their habitats date = 2020-06-13 pages = extension = .txt mime = text/plain words = 1395 sentences = 93 flesch = 54 summary = Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Here we compared the CpG and U content 327 of these coronaviruses and found that viruses that regularly infect AVP-rich tissues tend to Based on global sequence comparison, figure 4a shows that most SNPs are C->U substitutions. cache = ./cache/cord-327520-qj7coqfr.txt txt = ./txt/cord-327520-qj7coqfr.txt === reduce.pl bib === id = cord-325348-yi6yu5l1 author = Zhang, G. title = Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD date = 2020-06-17 pages = extension = .txt mime = text/plain words = 2664 sentences = 160 flesch = 54 summary = Recent cryo-electron microscopy (cryo-EM) structural studies of the SARS-CoV-2 spike protein 68 receptor binding domain (RBD) in complex with full-length human ACE2 receptor revealed key 69 amino acid residues at the contact interface between the two proteins and estimated the binding 70 affinity at ~15 nM [7, 8] . The results of this MD simulation suggest 108 that SBP1 and SBP2 peptides derived from the ACE-PD α1 helix may alone potentially bind the 109 SARS-CoV-2 spike RBD protein with sufficient affinity to disrupt the associated PPI. However, competition was not observed when using non-biotinylated SBP1 pre-140 mixed in solution with Sino Biological insect-derived SARS-CoV-2-RBD, even with a 1000-fold 141 excess of the peptide (Fig. 3C, 3E ). In conclusion, a biotinylated peptide sequence derived from human ACE2 was found to 205 bind Sino Biological insect-derived SARS-CoV-2 spike protein RBD with micromolar affinity, but 206 did not associate with SARS-CoV-2-RBD variants obtained from other commercial sources. cache = ./cache/cord-325348-yi6yu5l1.txt txt = ./txt/cord-325348-yi6yu5l1.txt === reduce.pl bib === id = cord-326380-9ecsp66y author = Griesemer, Sara B title = Assessment of sample pooling for clinical SARS-CoV-2 testing date = 2020-05-27 pages = extension = .txt mime = text/plain words = 2234 sentences = 113 flesch = 52 summary = The greatest concern with this approach in a clinical setting is the potential for reduced sensitivity, particularly the risk of false negative results when weak positive samples are pooled. To investigate this possibility, detection rates in pooled samples were evaluated, with extensive assessment of pools containing weak positive specimens. Additionally, the percentage of positive samples at different viral loads, as assessed by Ct value, was reviewed across nine weeks of the pandemic, to determine if these weak positive specimens comprise a significant component of total tested specimens and whether the proportion has changed over the course of the pandemic. In contrast, for weak positive specimens in VTM transport media, nine-sample pools caused multiple replicates to return negative results. We then sought to assess what component of the total specimens tested are comprised of these weak positive specimens, to evaluate how much of an impact pooling might have overall on testing sensitivity across positive patient detection in the pandemic. cache = ./cache/cord-326380-9ecsp66y.txt txt = ./txt/cord-326380-9ecsp66y.txt === reduce.pl bib === id = cord-326337-s0fp5z1q author = Chan, Kui K. title = An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants date = 2020-10-19 pages = extension = .txt mime = text/plain words = 4573 sentences = 256 flesch = 54 summary = Deep mutagenesis of the isolated receptor-binding domain (RBD) by yeast surface display 44 has easily identified mutations in S that retain high expression and ACE2 affinity, yet are no longer bound 45 by monoclonal antibodies and confer resistance (19) . An alternative protein-based antiviral to monoclonal antibodies is to use soluble ACE2 (sACE2) as a 56 decoy to compete for receptor-binding sites on the viral spike (6, (22) (23) (24) (25) of diverse SARS-associated betacoronaviruses that use ACE2 for entry. The sequence 162 diversity observed among natural betacoronaviruses, which display high diversity at the ACE2 binding 163 site, is therefore replicated in the deep mutational scan, which predicts the SARS-CoV-2 spike tolerates 164 substantial genetic diversity at the receptor-binding site for function. From this accessible sequence 165 diversity SARS-CoV-2 might feasibly mutate to acquire resistance to monoclonal antibodies or 166 engineered decoy receptors targeting the ACE2-binding site. cache = ./cache/cord-326337-s0fp5z1q.txt txt = ./txt/cord-326337-s0fp5z1q.txt === reduce.pl bib === id = cord-325610-n3zb36am author = Postlethwait, John H. title = An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities date = 2020-09-02 pages = extension = .txt mime = text/plain words = 2690 sentences = 159 flesch = 50 summary = title: An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities To exploit zebrafish (Danio rerio) as a disease model to understand mechanisms regulating the RAAS and its relationship to COVID-19 comorbidities, we must first identify zebrafish orthologs and co-orthologs of human RAAS genes, and second, understand where and when these genes are expressed in specific cells in zebrafish development. Results further identified a specific intestinal cell type in zebrafish larvae as the site of expression for key RAAS components, including Ace, Ace2, the coronavirus co-receptor Slc6a19, and the Angiotensin-related peptide cleaving enzymes Anpep and Enpep. These results identify specific genes and cell types to exploit zebrafish as a disease model for understanding the mechanisms leading to COVID-19 comorbidities. SUMMARY STATEMENT Genomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics show that they act in a specialized intestinal cell type. cache = ./cache/cord-325610-n3zb36am.txt txt = ./txt/cord-325610-n3zb36am.txt === reduce.pl bib === id = cord-324344-dxuabscn author = Zhao, Xuesen title = LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2 date = 2020-04-05 pages = extension = .txt mime = text/plain words = 3152 sentences = 186 flesch = 48 summary = In an effort to search for the host cellular protein(s) mediating the differential 29 susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and 30 LY6E, three cellular proteins with known activity of interfering virus entry, expressed at 31 significantly higher levels in HepG2 cells. In an effort to search for the host cellular protein(s) mediating the differential 29 susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and 30 LY6E, three cellular proteins with known activity of interfering virus entry, expressed at 31 significantly higher levels in HepG2 cells. Finally, the findings that LY6E inhibits human CoV entry cannot be evaded by ectopic 284 expression of membrane-associated serine protease TMPRSS2 and compromised by AmphoB 285 treatment strongly indicate that LY6E modulates virus entry via a distinct mechanism from that 286 IFITM proteins do (Figs. cache = ./cache/cord-324344-dxuabscn.txt txt = ./txt/cord-324344-dxuabscn.txt === reduce.pl bib === id = cord-326866-nbd4arhx author = Fox, Charles W. title = The representation of women as authors of submissions to ecology journals during the COVID-19 pandemic date = 2020-05-29 pages = extension = .txt mime = text/plain words = 1947 sentences = 86 flesch = 55 summary = At these six ecology journals there is no evidence of a decline in the proportion of submissions that are authored by women (as either first or submitting author) since the start of the COVID-19 disruptions; the proportion of papers authored by women in the post-COVID period of 2020 has increased relative to the same period in 2019, and is higher than in the period pre-COVID in 2020. At these six ecology journals there is no evidence of a decline in the proportion of submissions that are authored by women (as either first or submitting author) since the start of the COVID-19 disruptions; the proportion of papers authored by women in the post-COVID period of 2020 has increased relative to the same period in 2019, and is higher than in the period pre-COVID in 2020. cache = ./cache/cord-326866-nbd4arhx.txt txt = ./txt/cord-326866-nbd4arhx.txt === reduce.pl bib === id = cord-325420-e9fjo7tl author = Xiao, Xia title = Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2 date = 2020-07-06 pages = extension = .txt mime = text/plain words = 1282 sentences = 78 flesch = 58 summary = Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Positive compounds from the initial screen were tested for their antiviral 120 efficacy against SARS-CoV-2 in Vero cells. Our data show that 24 of these compounds show significant 124 efficacy in inhibiting SARS-CoV-2 replication with sub micromolar IC50 for many of these 125 drugs such as nilotinib, clofazimine and raloxifene. This screen identified five new compounds that 187 are highly efficacious in inhibiting the viral replication of SARS-CoV-2 with SI >600. The positively identified drugs from this screen were used to perform dose response curves 220 against OC43 on LLC-MK2 and against SARS-CoV-2 using Vero cells as described below. cache = ./cache/cord-325420-e9fjo7tl.txt txt = ./txt/cord-325420-e9fjo7tl.txt === reduce.pl bib === id = cord-328636-1q71gjwt author = Arora, Kajal title = Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate date = 2020-05-19 pages = extension = .txt mime = text/plain words = 2249 sentences = 118 flesch = 55 summary = title: Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). In this study, we report the first successful self-assembly of the SARS CoV-2 VLP by co-expression of the S, E and M proteins in Saccharomyces cerevisiae expression platform. cerevisiae, recombinant construct for the expression of S and E protein, pYRE100_CSP_CEP_His and M protein, pYRI100_CMP_His construct were cotransformed into the host and the positive clones were selected on YNB-URA-LEU plates. Episomal constructs of S, E and M with His tag, pYRE100_CSP_His, pYRE100_CMP_His and pYRE100_CEP_His plasmid and host vector pYRE100 plasmid were transformed into proprietary protease deficient PYPD yeast expression strain using Lithium acetate/SS-DNA/PEG mediated protocol and transformants were selected over selective YNB Glucose minus URA plates. cache = ./cache/cord-328636-1q71gjwt.txt txt = ./txt/cord-328636-1q71gjwt.txt === reduce.pl bib === id = cord-325473-hrdanbn1 author = Ghahremanpour, Mohammad M. title = Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2 date = 2020-08-28 pages = extension = .txt mime = text/plain words = 2915 sentences = 205 flesch = 56 summary = 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 5 Thus, M pro is viewed as a promising target for anti SARS-CoV-2 drug design; it has been the focus of several studies since the pandemic has emerged. For instance, a molecular docking study suggested remdesivir as a potential therapeutic that could be used against SARS-CoV-2, 10 which was supported experimentally by an EC50 value of 23 μM in an infected-cell assay. Structural Basis for the Inhibition of SARS-CoV-2 Main Protease by Antineoplastic Drug Carmofur Crystal Structure of SARS-CoV-2 Main Protease Provides a Basis for Design of Improved α-Ketoamide Inhibitors Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition Structure-based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease Targeting the SARS-CoV-2 Main Protease to Repurpose Drugs for cache = ./cache/cord-325473-hrdanbn1.txt txt = ./txt/cord-325473-hrdanbn1.txt === reduce.pl bib === id = cord-327711-welf0eb1 author = Zhou, Daming title = Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient date = 2020-06-13 pages = extension = .txt mime = text/plain words = 4847 sentences = 290 flesch = 59 summary = Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19. A neutralisation test for EY6A based on quantitative PCR detection of virus in the supernatant bathing infected Vero E6 cells after 5 days of culture, showed a ~1000-fold reduction in virus signal (Methods, Extended Data Fig. 3 ) indicating that it is highly neutralising. To elucidate the epitope of EY6A, we determined the crystal structures of the deglycosylated SARS-CoV-2 RBD in complex with EY6A Fab alone and in a ternary complex incorporating a nanobody (Nb) which has been shown to compete with ACE2 (for data on a closely related Nb see Huo 2020, submitted), as a crystallisation chaperone. cache = ./cache/cord-327711-welf0eb1.txt txt = ./txt/cord-327711-welf0eb1.txt === reduce.pl bib === id = cord-328073-bqeffvzl author = Limonta, Daniel title = Nodosome inhibition as a novel broad-spectrum antiviral strategy against arboviruses and SARS-CoV-2 date = 2020-11-06 pages = extension = .txt mime = text/plain words = 1878 sentences = 113 flesch = 55 summary = The studies were prompted by the observation that infection of human fetal brain cells with Zika virus (ZIKV) induces expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a host factor that was found to promote ZIKV replication and spread. A drug that targets NOD2 was shown to have potent broad-spectrum antiviral activity against other flaviviruses, alphaviruses and SARS-CoV-2, the causative agent of COVID-19. Next, we demonstrated that the NOD2 inhibitor GSK717 blocks infection by and 205 spread of ZIKV in human fetal brain and cell lines. Similarly, the work here which demonstrated the antiviral activity of NOD2 and RIPK2 inhibitors using tissue explants, 216 primary cells and cell lines, support the potential clinical use of these compounds in mono or co-217 infections by arboviruses as well as coronavirus infections at early and/or advanced stages. Calu-3 and Huh7 cells infected with SARS-CoV-2 (MOI=0.1) were also treated with GSK583 for 24 hours before collecting the cell supernatants for viral titer determination. cache = ./cache/cord-328073-bqeffvzl.txt txt = ./txt/cord-328073-bqeffvzl.txt === reduce.pl bib === id = cord-326736-jd6fvaop author = Bosco-Lauth, Angela M. title = Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats date = 2020-05-29 pages = extension = .txt mime = text/plain words = 922 sentences = 68 flesch = 50 summary = title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naïve cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. The first report of reverse zoonosis, or transmission from human to animal, was reported 46 from Hong Kong, where a COVID patient's dog tested PCR positive for SARS2 multiple times 47 (Sit et al. Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of 414 COVID-19 patients in a veterinary campus Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2 Transmission of 422 SARS-CoV-2 in Domestic Cats cache = ./cache/cord-326736-jd6fvaop.txt txt = ./txt/cord-326736-jd6fvaop.txt === reduce.pl bib === id = cord-328257-kl4wh2zg author = Xu, H title = Hydroxychloroquine increased psychiatric-like behaviors and disrupted the expression of related genes in the mouse brain date = 2020-09-28 pages = extension = .txt mime = text/plain words = 4851 sentences = 217 flesch = 54 summary = Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. Less attention has been paid to the effects of HCQ on mental health, although multiple studies have reported severe psychiatric symptoms, including agitation, hallucinations, anxiety, depression, and suicidal ideation, in patients treated with HCQ or chloroquine (9) (10) (11) (12) . To the best of our knowledge, this study is the first to test the psychiatric effect of HCQ in an animal model, and our results suggest that, in healthy mice, HCQ administration can induce persistent behavioral changes and disrupt gene expression in the brain. Our results did not reveal a significant effect of HCQ treatment on working memory, but total exploration time was decreased after HCQ administration, which also suggests that the drugs increased anxiety. cache = ./cache/cord-328257-kl4wh2zg.txt txt = ./txt/cord-328257-kl4wh2zg.txt === reduce.pl bib === id = cord-323967-2mo915u1 author = Miersch, Shane title = Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations date = 2020-11-01 pages = extension = .txt mime = text/plain words = 3231 sentences = 173 flesch = 57 summary = Moreover, structural studies reveal that the best nAb targets the host receptor binding site of the virus spike protein, and thus, its tetravalent version can block virus infection with a potency that exceeds that of the bivalent IgG by an order of magnitude. Moreover, the use of a highly stable framework 77 enabled facile and modular design of ultra-high affinity nAbs in tetravalent formats that retained 78 favorable drug-like properties and exhibited neutralization potencies that greatly exceeded those 79 of the bivalent IgG format. Fab-phage were screened by ELISA and those that exhibited >50% loss in binding 92 to RBD in the presence of 200 nM ACE2 were sequenced, revealing 34 unique clones (Fig. 1A) , 93 deemed to be potential nAbs and converted into the full-length human IgG1 format for 94 purification and functional characterization. cache = ./cache/cord-323967-2mo915u1.txt txt = ./txt/cord-323967-2mo915u1.txt === reduce.pl bib === id = cord-328189-jpkxjn6e author = Brielle, Esther S. title = The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor date = 2020-03-12 pages = extension = .txt mime = text/plain words = 2971 sentences = 172 flesch = 53 summary = We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. Herein, we analyze the binding of several CoV RBDs to ACE2 with molecular dynamics (MD) simulations and compare the stability, relative interaction strength, and dynamics of the interaction between the viral spike protein and the human ACE2 receptor. While the sequence identity between the RBDs of COVID-19 and SARS-2002 is 73% (Table 1) , we observe a significantly higher residue substitution rate at the interaction interface with the ACE2 receptor. Our MD simulation analysis reveals that the SARS-des has a substantially lower interaction scores with ACE2 (median of -2199.2, Fig. S2) , as expected for an optimized human ACE2-binding RBD design. We relied on the crystal structure of the spike protein receptor-binding domain from a SARS coronavirus designed human strain complexed with the human receptor ACE2 (PDB 3SCI, resolution 2.9Å) as a template for comparative modeling. cache = ./cache/cord-328189-jpkxjn6e.txt txt = ./txt/cord-328189-jpkxjn6e.txt === reduce.pl bib === id = cord-326257-rcv8sh22 author = Simmonds, P. title = Rampant C->U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses – causes and consequences for their short and long evolutionary trajectories date = 2020-05-01 pages = extension = .txt mime = text/plain words = 3499 sentences = 172 flesch = 47 summary = C->U transitions underpinned almost half of the amino acid differences between SARS-CoV-2 variants, and occurred preferentially in both 5'U/A and 3'U/A flanking sequence contexts comparable to favoured motifs of human APOBEC3 proteins. Importance The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short and long term evolution. The possibility that the initial diversity within a viral population was largely host-induced would have major implications for 70 evolutionary reconstruction of SARS-CoV-2 variants in the current pandemic, as well as in our understanding both of host antiviral pathways against coronaviruses and the longer term shaping effects on their genome composition. To formally analyse 105 the excess of C->U transitions we calculated an index of asymmetry (frequency[C->U] / f[U->C]) x (fU/fC) and compared this with degrees of sequence divergence and dN/dS ratio in SARS-CoV-2 and other coronavirus datasets (Fig. 2B, 2C ). cache = ./cache/cord-326257-rcv8sh22.txt txt = ./txt/cord-326257-rcv8sh22.txt === reduce.pl bib === id = cord-326666-melz5fq4 author = Sun, Weitao title = The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe date = 2020-09-03 pages = extension = .txt mime = text/plain words = 1723 sentences = 138 flesch = 62 summary = title: The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe This study shows that the host-genome similarity (HGS) of SARS-CoV-2 is significantly higher than that of SARS-CoV, especially in the ORF6 and ORF8 genes encoding proteins antagonizing innate immunity in vivo. This finding implies that high HGS of SARS-CoV-2 genome may further inhibit IFN I synthesis and cause delayed host innate immunity. An ORF1ab mutation, 10818G>T, which occurred in virus populations with high HGS but rarely in low-HGS populations, was identified in 2594 genomes with geolocations of China, the USA and Europe. 578 shown with special markers at the top of colored blocks representing ORFs. Mutation 623 10818G>T in ORF1ab (codon TTG>TTT) occurred in populations with high HGS, which 624 results in amino acid M37F mutation in transmembrane protein nsp6. ORF1ab (codon TTG>TTT) occurred in populations with high HGS, which results in amino 631 acid M37F mutation in transmembrane protein nsp6. cache = ./cache/cord-326666-melz5fq4.txt txt = ./txt/cord-326666-melz5fq4.txt === reduce.pl bib === id = cord-329240-atisrhas author = Fedorenko, Aliza title = Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces date = 2020-06-16 pages = extension = .txt mime = text/plain words = 4493 sentences = 233 flesch = 50 summary = Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic. To study virus survival in microdroplets deposited on a smooth inanimate surface, we sprayed Phi6, MS2, and PhiX174 viruses suspended in three media -human saliva, water, and SM bufferon glass-bottom 12-well plates (Fig. 1, Methods) . The observation that at a given RH, the microscopic hydration conditions of deposited droplets of various media can differ so widely (see along the rows of Fig. 3 ) suggests that RH does not directly affect virus stability and infectivity in drying microdroplets deposited on surfaces, but rather RH indirectly affects survival through its effect on physicochemical conditions at the scale that matters for viruses (~ µm). cache = ./cache/cord-329240-atisrhas.txt txt = ./txt/cord-329240-atisrhas.txt === reduce.pl bib === id = cord-328960-46zui1sl author = Hillen, Hauke S. title = Structure of replicating SARS-CoV-2 polymerase date = 2020-04-27 pages = extension = .txt mime = text/plain words = 4541 sentences = 285 flesch = 62 summary = Particle classification yielded a 3D reconstruction at a nominal resolution of 2.9 Å and led to a refined structure of the RdRp-RNA complex (Extended Data Figures 1 and 2) . The structure resembles that of the free enzyme 16 , but also reveals large additional protein regions in nsp8 that became ordered upon RNA binding and interact with RNA far outside the core enzyme (Extended Data Figure 3a ). The supernatant containing nsp12 was filtered using a 5-μm syringe filter, followed by filtration with a 0.8-µm syringe filter (Millipore) and applied onto a HisTrap HP 5 mL (GE Healthcare), preequilibrated in lysis buffer (300 mM NaCl, 50 mM Na-HEPES pH 7.4, 10 % (v/v) glycerol, 30 mM imidazole pH 8.0, 3 mM MgCl2, 5 mM β-mercaptoethanol, 0.284 µg ml-1 leupeptin, 1.37 µg ml-1 pepstatin, 0.17 mg ml-1 PMSF, and 0.33 mg ml-1 benzamidine). cache = ./cache/cord-328960-46zui1sl.txt txt = ./txt/cord-328960-46zui1sl.txt === reduce.pl bib === id = cord-327431-dnppshnv author = Hognon, Cécilia title = Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses date = 2020-05-27 pages = extension = .txt mime = text/plain words = 2460 sentences = 133 flesch = 48 summary = In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. 28, 37 In this letter, we report an extended all-atom molecular dynamics (MD) study of the interactions produced between a dimeric SUD domain and a short RNA G4 sequence. To further examine the conformational space spanned by the G4/SUD complex, and in particular the role of the RNA in favoring the dimerization and the structure of the interface, we resorted to enhanced sampling MD simulations to obtain the 2D free energy profile along two relevant collective variables: first, the distance between G4 and SUD, and second, the separation between the two SUD subdomains. cache = ./cache/cord-327431-dnppshnv.txt txt = ./txt/cord-327431-dnppshnv.txt === reduce.pl bib === id = cord-326882-bbn1tfq5 author = Li, Quan title = Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations date = 2020-04-14 pages = extension = .txt mime = text/plain words = 1675 sentences = 104 flesch = 55 summary = We set out to examine genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARSCoV-2. To explore the variability in genetic polymorphisms and expression in human ACE2 (hACE2), we set out to determine if there were any differences between the Asian and Caucasian populations for ACE2 polymorphisms and compare the variability of hACE2 expression in peripheral blood among eight different populations. In order to investigate whether differences in genetic variations exist between Caucasians and Asians and if these variants can influence the efficiency of cell entry of SARS-CoV-2, we retrieved the variants in the hACE2 from gnomAD v2.1 exomes13. Asians and Other Races Express Similar Levels of and Share the Same Genetic Polymorphisms of the SARS-CoV-2 Cell-Entry Receptor cache = ./cache/cord-326882-bbn1tfq5.txt txt = ./txt/cord-326882-bbn1tfq5.txt === reduce.pl bib === id = cord-327808-k3jec87p author = Zhu, Yunkai title = The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission date = 2020-08-25 pages = extension = .txt mime = text/plain words = 2754 sentences = 155 flesch = 61 summary = We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. The sequence at the S1/S2 boundary contains a cleavage site for the furin protease, 61 which could preactivate the S protein for membrane fusion and potentially reduce the 62 dependence of SARS-CoV-2 on plasma membrane proteases, such as transmembrane 63 serine protease 2 (TMPRSS2), to enable efficient cell entry (Shang et al., 2020) . Intriguingly, 188 these genes edited also significantly inhibited the infection by pseudovirus bearing the 189 spike protein of MERS-CoV in A549-ACE2-DPP4 cells ( Figure 3D ). Although no infectious virus was detected by focus-forming 299 assay (data not shown), viral RNA levels were higher in fecal samples for Sfull (20 and 300 40-fold) than Sdel at days 2 and 4, respectively ( Figure 5B ). cache = ./cache/cord-327808-k3jec87p.txt txt = ./txt/cord-327808-k3jec87p.txt === reduce.pl bib === id = cord-330031-c1n994j6 author = Kratzel, Annika title = Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols date = 2020-03-17 pages = extension = .txt mime = text/plain words = 752 sentences = 51 flesch = 50 summary = title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. We show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission. The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-2 CoV-2) causing COVID-19 is a major burden for health care systems worldwide. The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-2 CoV-2) causing COVID-19 is a major burden for health care systems worldwide. We therefore determined the virucidal activity of two 5 alcohol-based hand rub solutions for hand disinfection recommended by the World 6 Hand Hygiene in Health Care' suggests two alcohol-based formulations for hand 9 sanitization to reduce pathogen infectivity and spreading. cache = ./cache/cord-330031-c1n994j6.txt txt = ./txt/cord-330031-c1n994j6.txt === reduce.pl bib === id = cord-326441-w8iyh59u author = Bhattacharjee, Sayan title = Transmission of allosteric response within the homotrimer of SARS-CoV-2 spike upon recognition of ACE2 receptor by the receptor-binding domain date = 2020-09-06 pages = extension = .txt mime = text/plain words = 2426 sentences = 129 flesch = 48 summary = The pathogenesis of novel SARS-CoV-2 virus initiates through recognition of ACE2 receptor (Angiotensin-converting enzyme 2) of the host cells by the receptor-binding domain (RBD) located at spikes of the virus. Using MD simulations, we have demonstrated allosteric crosstalk within RBD in apoand receptor-bound states where dynamic correlated motions and electrostatic energy perturbations contribute. To probe deeper into the dynamicity of free and ACE2-bound RBD of the COVID spike protein, Cα atoms based root mean square fluctuations (RMSF) and Order parameter (S 2 ) considering the N-H vectors 9 of RBD, were calculated from the corresponding trajectories. The residue wise non-bonded interaction energy between free RBD and its bound state with ACE2 was described as: Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor cache = ./cache/cord-326441-w8iyh59u.txt txt = ./txt/cord-326441-w8iyh59u.txt === reduce.pl bib === id = cord-330473-f03ka7bd author = Yuan, Meng title = A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV date = 2020-03-14 pages = extension = .txt mime = text/plain words = 1563 sentences = 107 flesch = 65 summary = In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain. A recent study has shown that CR3022, which is a human 49 neutralizing antibody that targets the receptor-binding domain (RBD) of SARS-CoV (4), Nonetheless, despite having a 70 high conservation in the epitope residues, CR3022 Fab binds to SARS-CoV RBD (K d = 1 71 nM) with a much higher affinity than to SARS-CoV-2 RBD (K d = 115 nM) (Table 1 Previous cryo-EM studies have also shown that the recombinant SARS-CoV S 121 protein is mostly found in the none-"up", single-"up", or double-"up" conformations (19, 122 21), but rarely in the triple-"up" conformation, even with ACE2 receptor bound (21, 22) . cache = ./cache/cord-330473-f03ka7bd.txt txt = ./txt/cord-330473-f03ka7bd.txt === reduce.pl bib === id = cord-331611-pwj226j0 author = Shrimp, Jonathan H. title = An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19 date = 2020-06-23 pages = extension = .txt mime = text/plain words = 3894 sentences = 216 flesch = 45 summary = We demonstrate effectiveness to quantify inhibition down to subnanomolar concentrations by assessing the inhibition of camostat, nafamostat and gabexate, clinically approved agents in Japan for pancreatitis due to their inhibition of trypsin-like proteases. The structurally related trypsin-like serine protease inhibitor nafamostat was shown to similarly inhibit spike protein-mediated cell fusion of MERS-CoV 7 . Herein we report the development of a TMPRSS2 fluorogenic biochemical assay and testing of clinical repurposing candidates for COVID19. To identify inhibitors of TMPRSS2 that may be used to validate its role in SARS-CoV-2 entry and potentially expedite to clinical trials, we developed a biochemical assay using active TMPRSS2 protease and a fluorogenic peptide substrate ( Figure 1B) . We developed a fluorogenic biochemical assay for measuring recombinant human TMPRSS2 activity for high-throughput screening that can be readily replicated and used to demonstrate that nafamostat is a more potent inhibitor than camostat and gabexate. cache = ./cache/cord-331611-pwj226j0.txt txt = ./txt/cord-331611-pwj226j0.txt === reduce.pl bib === id = cord-328585-1rkrrx8a author = Lu, Shuai title = The immunodominant and neutralization linear epitopes for SARS-CoV-2 date = 2020-08-27 pages = extension = .txt mime = text/plain words = 2954 sentences = 254 flesch = 69 summary = To investigate the spectrum of antibodies in COVID-19 patients, we detected the binding of the 155 early convalescent sera of 8 imported (Europe) cases which infected SARS-CoV-2 in early April, 156 2020 and 12 domestic (China) cases in early February, 2020 to various epitopes ( Table 1) K203R204/G189R203G204/R203G204/R203G204S344 in N protein, respectively (Table 1) , 172 resulting in different immunodominant epitopes of different virus sub-strains which provide the 173 bases for the differential diagnosis. The predicted epitopes induce neutralization antibody production 175 SARS-CoV-2 pseudo-virus neutralization assay is a well-accepted method to detect the ability of 176 vaccine to inhibit SARS-CoV-2 infection . To assess 8 neutralization antibodies induced by S protein epitopes, we incubated the immunization sera with 178 D614 or G614 SARS-CoV-2 pseudo-viruses and then the mixture was added to ACE2-293FT 179 cells which stably expressed ACE2. cache = ./cache/cord-328585-1rkrrx8a.txt txt = ./txt/cord-328585-1rkrrx8a.txt === reduce.pl bib === id = cord-328695-nptfd6c2 author = Tengs, Torstein title = A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species date = 2020-06-29 pages = extension = .txt mime = text/plain words = 1969 sentences = 102 flesch = 51 summary = title: A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species We document here the presence of s2m, a highly conserved, mobile genetic element with unknown function, in both the SARS-CoV-2 genome and a large number of insect genomes. Although s2m is not universally present among coronaviruses and appears to undergo horizontal transfer, the high sequence conservation and universal presence of s2m among isolates of SARS-CoV-2 indicate that, when present, the element is essential for viral function. The presence of s2m in the SARS-CoV-2 genome (GenBank accession MN908947, position 29727-29768) and other members of this group is probably the result of a single horizontal transfer event, predating the divergence of the SARS-related viruses (Tengs, et al. The insect species that contain s2m (and the associated protein) are distantly related, indicating either a deep evolutionary origin with multiple losses or that this genetic construct is also a mobile element, perhaps using viruses as a vector . cache = ./cache/cord-328695-nptfd6c2.txt txt = ./txt/cord-328695-nptfd6c2.txt === reduce.pl bib === id = cord-330213-reb9vo7x author = Miladi, Milad title = The landscape of SARS-CoV-2 RNA modifications date = 2020-07-18 pages = extension = .txt mime = text/plain words = 3213 sentences = 210 flesch = 55 summary = From sequencing three isolates, we derive a robust identification of SARS-CoV-2 modification sites within a physiologically relevant host cell type. A comparison of our data with the DRS data from a previous SARS-CoV-2 isolate, both raised in monkey renal cells, reveals consistent RNA modifications across the viral genome. The long RNA sequencing reads generated for this study cover the entire SARS-CoV-2 genomic RNA as well as the different ORFs (Fig 1b,c, Fig. S1b ). Two sets of Galaxy workflows based on Tombo (16) and Nanocompore (17) tools were designed to compute the modification scores from the DRS data (Table S3) . Figure 5 : Direct RNA sequencing raw electrical signals of downsampled reads obtained from unmodified RNA (IVT, black), from samples generated for this study and from isolate from a published korean data set (Fr1-3 and Kr, red). cache = ./cache/cord-330213-reb9vo7x.txt txt = ./txt/cord-330213-reb9vo7x.txt === reduce.pl bib === id = cord-330384-yujbcwg5 author = Al-Mulla, Fahd title = A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine date = 2020-05-16 pages = extension = .txt mime = text/plain words = 4684 sentences = 249 flesch = 52 summary = The increased cleavage activity of this protease was suggested to diminish viral recognition by neutralizing antibodies and by activating SARS spike (S) protein for virus-cell fusion 11 and facilitates the active binding of SARS-CoV-2 through ACE2 receptor, which is a risk factor for a more serious COVID-19 presentation [8] [9] [10] . Recent studies, assessed the genetic variations and eQTL (expression quantitative trait locus) expression profiles in the candidate genes ACE2, TMPRSS2, and FURIN to demonstrate the sex and population-wise differences that may influence the pathogenicity of SARS-CoV-2 9, [15] [16] [17] [18] [19] . Therefore, we screened the genetic variations and eQTL expression of the SARS-CoV-2 candidate genes, ACE2, TMPRSS2 and FURIN in three Middle Eastern populations: Kuwaiti, Iranian, and Qatari and compared them to available MAF data in the gnomAD database 41 . cache = ./cache/cord-330384-yujbcwg5.txt txt = ./txt/cord-330384-yujbcwg5.txt === reduce.pl bib === id = cord-332178-0xyrmk5a author = Chadchan, Sangappa B. title = The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization date = 2020-06-24 pages = extension = .txt mime = text/plain words = 2449 sentences = 163 flesch = 50 summary = title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. Given the important function of the uterine stroma and the possibility that SARS-CoV-2 could infect the uterus, our goal here was to 101 determine whether ACE2 is expressed in endometrial stromal cells, is regulated by progesterone, 102 and is required for decidualization. Given the high ACE2 expression in the human 143 endometrium, SARS-CoV-2 may be able to enter endometrial stromal cells and elicit pathological 144 manifestations in women with COVID-19. cache = ./cache/cord-332178-0xyrmk5a.txt txt = ./txt/cord-332178-0xyrmk5a.txt === reduce.pl bib === id = cord-329118-0gq5yusk author = Xiang, Boyu title = ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway date = 2020-06-06 pages = extension = .txt mime = text/plain words = 1545 sentences = 83 flesch = 55 summary = The purpose of our study is to explore cell cluster structure and ACE2 expression pattern in the bladder and use scRNA-seq to infer the effects of human senile lesions, OAB, on umbrella cells and intermediate cells in the bladder epithelium from the results of mice. Because this potential urinary tract infection pathway may be critical to prevent 2019n-Cov, here we used two scRNA-Seq transcriptomes to analyze bladder tissue from normal and OAB mice and combined human and mouse bladder ACE2 expression data from public data base to analyze the impact of underlying disease on this potential infectious system 7 . Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection cache = ./cache/cord-329118-0gq5yusk.txt txt = ./txt/cord-329118-0gq5yusk.txt === reduce.pl bib === id = cord-329102-2y49kcwu author = Lan, Tammy C. T. title = Structure of the full SARS-CoV-2 RNA genome in infected cells date = 2020-06-30 pages = extension = .txt mime = text/plain words = 9315 sentences = 507 flesch = 61 summary = We evaluated the robustness of our in-cell data derived genome-wide model by varying two critical RNA folding parameters used by RNAstructure: 1) the maximum allowed distance for base pairing and 2) the threshold for DMS signal normalization. Previous studies that computationally predicted genome-wide SARS-Cov-2 RNA structures used 1) RNAz, a thermodynamic-based model that additionally takes sequence alignment and considers base pairing conservation (Gruber et al., 2010; Rangan, Zheludev and Das, 2020) , and 2) Contrafold, which predicts RNA secondary structures without physics-based models and instead uses learned parameters based on known structures (Do, Woods and Batzoglou, 2006) . Interestingly, in silico predictions of the RNA structure of the SARS-CoV-2 genome using RNAz (Rangan, Zheludev and Das, 2020) and ScanFold (Andrews et al., 2020) do not find the 3-stem pseudoknot but instead support our in-cell model of Alternative Stem 1. cache = ./cache/cord-329102-2y49kcwu.txt txt = ./txt/cord-329102-2y49kcwu.txt === reduce.pl bib === id = cord-328187-9zd79gai author = Zhang, Yali title = Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors date = 2020-07-22 pages = extension = .txt mime = text/plain words = 3018 sentences = 165 flesch = 55 summary = The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. 22 On 293T-ACE2iRb3 cells, both the SARS-CoV2-RBG and SARS-CoV2-STG 23 probes showed effective-binding to the cells, as membrane-bound and hACE2-24 mRuby3-colocalized mGam signals were observed after a 6-min incubation with the 25 cells ( Figure 2C ). Compared with 3 samples from healthy donors (n=40), all COVID-19-convalescent plasmas showed 4 significant cMFI inhibition on CSBT assay, whereas only 12 samples (37.5%) had 5 detectable CRBT activity ( Figure 3A ). Among the antibody titers derived from various assays, the 10 CSBT titer showed the best correlation with LVppNAT ( Figure 3D and Table S2, 11 r=0.832, p<0.001), and it also well correlated (r=0.959, p<0.001, Figure 3D ) with the 12 neutralization activity against authentic SARS-CoV-2 virus in 12 representative 13 samples (Table S3) . cache = ./cache/cord-328187-9zd79gai.txt txt = ./txt/cord-328187-9zd79gai.txt === reduce.pl bib === id = cord-328644-odtue60a author = Comandatore, Francesco title = Insurgence and worldwide diffusion of genomic variants in SARS-CoV-2 genomes date = 2020-05-28 pages = extension = .txt mime = text/plain words = 6535 sentences = 301 flesch = 50 summary = These variants might arise during the spread of the epidemic, as viruses are known for their high frequency of mutation, particularly in single stranded RNA viruses -as in the case of SARS-CoV-2 (Sanjuán and Domingo-Calap 2016) , which has a single, positive-strand RNA genome. To have a better insight on the history and spread of the COVID-19 pandemic in Italy and thanks to the sequences deposited in the Gisaid database, we identified 7 non synonymous mutations that are differentially frequent in Italian SARS-CoV-2 strains respect to strains circulating globally. Our analysis allowed us to identify 7 positions in four proteins that present drastic changes in amino acid frequencies when comparing Italian sequences with worldwide sequences available on Gisaid.org on April, 10, 2020 ( Figure 1 ). cache = ./cache/cord-328644-odtue60a.txt txt = ./txt/cord-328644-odtue60a.txt === reduce.pl bib === id = cord-331701-izkz1hz4 author = Eden, John-Sebastian title = An emergent clade of SARS-CoV-2 linked to returned travellers from Iran date = 2020-03-17 pages = extension = .txt mime = text/plain words = 1271 sentences = 70 flesch = 50 summary = Phylogenetic analyses of whole genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases. Herein, we show that the genomic analyses of SARS-CoV-2 strains from Australian returned travellers with COVID-19 disease may provide important insights into viral diversity present in regions currently lacking genomic data. However, while we cannot completely discount that the cases in Australia and New Zealand came from other sources including China, our phylogenetic analyses, as well as epidemiological (recent travel to Iran) and clinical data (date of symptom onset), provide evidence that this clade of SARS-CoV-2 is linked to the Iranian epidemic, from where genomic data is currently lacking. cache = ./cache/cord-331701-izkz1hz4.txt txt = ./txt/cord-331701-izkz1hz4.txt === reduce.pl bib === id = cord-332185-a96r1k7a author = Zhang, Shuyuan title = Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution date = 2020-09-22 pages = extension = .txt mime = text/plain words = 1228 sentences = 103 flesch = 63 summary = title: Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. Cryo-electron microscopy structures of the SARS-CoV spike 464 glycoprotein reveal a prerequisite conformational state for receptor binding Cryo-EM structure of the SARS 467 coronavirus spike glycoprotein in complex with its host cell receptor ACE2 Cryo-EM structures of MERS-CoV and SARS-CoV spike 495 glycoproteins reveal the dynamic receptor binding domains cache = ./cache/cord-332185-a96r1k7a.txt txt = ./txt/cord-332185-a96r1k7a.txt === reduce.pl bib === id = cord-327912-wfjdxgxh author = Swann, Heather title = Minimal system for assembly of SARS-CoV-2 virus like particles date = 2020-08-24 pages = extension = .txt mime = text/plain words = 1695 sentences = 98 flesch = 59 summary = Here we demonstrate that non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled by co-expressing the viral proteins S, M and E in mammalian cells. Non-infectious virus like particles (VLPs) displaying essential viral proteins can be used to study the structural properties of the SARS-CoV-2 virions and due to their maximum immunogenicity are also vaccine candidates 2, 3 . Similarly, expression of M, E and S proteins are shown to result in release of morphologically identical particles to wild type SARS-CoV virus 9, 10 . We then tested the structural integrity of the SARS-CoV-2 VLPs attached to dry glass using Atomic Force Microscopy (AFM), since SARS-CoV-2 virions have been reported to survive on solid surfaces in dry conditions for many hours 13 . SARS-CoV-2 M, S and E protein genes were identified from the full genome sequence of the virus 1 , these genes were then humanized and inserted in CMV driven mammalian expression vectors (see supplement for complete plasmid sequences). cache = ./cache/cord-327912-wfjdxgxh.txt txt = ./txt/cord-327912-wfjdxgxh.txt === reduce.pl bib === id = cord-332134-88wfcc3y author = Li, Tingting title = A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection date = 2020-09-24 pages = extension = .txt mime = text/plain words = 2051 sentences = 158 flesch = 57 summary = title: A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection Molecular mechanism for neutralization 157 Structure alignment of SR4-, MR17-and ACE2-RBD 4 showed that both sybodies 158 engage with RBD at the receptor-binding motif (RBM) ( Fig. 2A, 2B) . Taken together, SR4 169 and MR17, and probably MR3, neutralize SARS-CoV-2 by competitively blocking the For biparatopic fusion, we first identified two sybodies, namely LR1 and LR5 (Fig. 208 3A, 3B), that could bind RBD in addition to MR3 using the BLI assay. As LR5 showed 209 higher affinity and neutralization activity than LR1 (Fig. 1A) , we fused this non-210 competing sybody to the N-terminal of MR3 with various length of GS linkers ranging 211 from 13 to 34 amino acids (Extended Data Table S1 ). Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with 803 cache = ./cache/cord-332134-88wfcc3y.txt txt = ./txt/cord-332134-88wfcc3y.txt === reduce.pl bib === id = cord-329504-91te3nu8 author = Croll, Tristan title = Making the invisible enemy visible date = 2020-10-07 pages = extension = .txt mime = text/plain words = 4826 sentences = 219 flesch = 52 summary = A general indication of how well the atomic model fits the measurement data can be obtained by comparing the deposited R-factors to results from PDB-REDO (10) (including Whatcheck (11)) to determine the overall density fit as well as many other diagnostics. Our remodelled structure is offering a valuable structural basis for future studies, such as in-silico docking and drug design targeting at SARS-CoV-2 RdRp (34), as well as for computational modelling or simulations to investigate the molecular mechanism of viral replication (31, 35, 36) . This has included a number of posts on our homepage aimed at non-scientists and live streaming the reprocessing of data on Twitch, as well as the design, production, and public release of an accurate 3D printed model of SARS-CoV-2 based on deposited structures for use as a prop for outreach activities. cache = ./cache/cord-329504-91te3nu8.txt txt = ./txt/cord-329504-91te3nu8.txt === reduce.pl bib === id = cord-330743-o11d0aa1 author = Yu, Xi title = Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date = 2020-05-25 pages = extension = .txt mime = text/plain words = 4470 sentences = 245 flesch = 54 summary = Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Incubation of the culture supernatant but not the bacterial lysates resulted in significant suppression of DENV ( Figure 1B ) and ZIKV ( Figure 1C ) infectivity in Vero cells, indicating that an extracellular effector(s) secreted by Csp_BJ was responsible for viral inhibition. DENV, ZIKV, HSV-1 and SARS-CoV-2 virus stocks were diluted to 50 plaque-forming units (pfu) per ml and incubated untreated or with a serial dilution of the CbAEs in five-fold steps at 37°C for 1 hr before being added onto Vero cell monolayers for 2 hr of infection. cache = ./cache/cord-330743-o11d0aa1.txt txt = ./txt/cord-330743-o11d0aa1.txt === reduce.pl bib === id = cord-329395-4k8js9v2 author = Ratcliff, Jeremy title = Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA date = 2020-07-01 pages = extension = .txt mime = text/plain words = 1662 sentences = 124 flesch = 55 summary = Polymerase chain reaction (PCR)-based assays are the gold standard for detecting viral RNA in patient samples and are used extensively in clinical settings. To enable the application of PCR in resource-poor or non-specialist laboratories, we have developed and evaluated a nested PCR method for SARS-CoV-2 RNA using simple agarose gel electrophoresis for product detection. Using clinical samples tested by conventional qPCR methods and RNA transcripts of defined RNA copy number, the nested PCR based on the RdRP gene demonstrated high sensitivity and specificity for SARS-CoV-2 RNA detection in clinical samples, but showed variable and transcript length-dependent sensitivity for RNA transcripts. The sensitivity of the nested PCR and two RT-qPCR methods was compared by measuring the 118 50% endpoints (50EP) of detection for serial dilutions of the four transcripts described above 119 (Table 1, Figure 2 ). Protocol: Real-time RT-PCR assays for the detection of SARS-CoV-2 cache = ./cache/cord-329395-4k8js9v2.txt txt = ./txt/cord-329395-4k8js9v2.txt === reduce.pl bib === id = cord-329840-f3dsu36p author = Hati, Sanchita title = Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date = 2020-05-11 pages = extension = .txt mime = text/plain words = 2497 sentences = 173 flesch = 51 summary = In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. In the backdrop of significant mortality rate for SARS-CoV-2 (hereinafter referred to as CoV-2) infection, it is important to know if the thiol-disulfide balance plays any role on the binding of the spike glycoprotein on to the host cell receptor protein ACE2. Using these reported structures, molecular dynamics simulations and electrostatic field calculations were performed to explore the impact of thioldisulfide balance on CoV/CoV-2 and ACE2 binding affinities. The structural and dynamical changes due to the change in the redox states of cysteines in the interacting proteins were analyzed and their effects on binding free energies were studied. cache = ./cache/cord-329840-f3dsu36p.txt txt = ./txt/cord-329840-f3dsu36p.txt === reduce.pl bib === id = cord-330337-d41imvo7 author = Basu, Souradip title = Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date = 2020-10-20 pages = extension = .txt mime = text/plain words = 6428 sentences = 311 flesch = 52 summary = Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. The secondary structure of the wild type and the mutant proteins along with their degree of disordered residues and accessible surface area was predicted using the primary sequence of the protein. Each of the seven proteins were assigned a score of either '-1' or '0', for each of the four computational tools used for epitope prediction, where '-1' corresponds to any change in number or binding efficacy of antigenic determinants, that may have surfaced because of mutation and '0' corresponds to no changes between wild type and mutant forms. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure cache = ./cache/cord-330337-d41imvo7.txt txt = ./txt/cord-330337-d41imvo7.txt === reduce.pl bib === id = cord-329129-t84pu00z author = Zuo, J title = Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection date = 2020-11-02 pages = extension = .txt mime = text/plain words = 3486 sentences = 175 flesch = 50 summary = We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection. In this study we characterised SARS-CoV-2-specific T cell immune responses in a cohort of 100 donors at 6-months post-infection. Peptide pools from a range of viral proteins, including spike, nucleoprotein and membrane protein, were used to stimulate fresh PBMC and the magnitude of the global SARS-CoV-2-specific T-cell response was determined. Here we undertook, to our knowledge, the first assessment of the SARS-CoV-2-specific T cell immune response at six months following primary infection in a unique cohort of healthy adults with asymptomatic or mild-to-moderate COVID-19. cache = ./cache/cord-329129-t84pu00z.txt txt = ./txt/cord-329129-t84pu00z.txt === reduce.pl bib === id = cord-331786-wgt7kg6f author = Diego-Martin, Borja title = Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities date = 2020-10-13 pages = extension = .txt mime = text/plain words = 7034 sentences = 326 flesch = 45 summary = For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. In parallel, we also produced the recombinant SARS-CoV-2 N protein and its Receptor Binding Domain (RBD) in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Finally, we performed sandwich ELISA tests of sybody17 and nanobody72 ( Fig 5E and Fig 5F, respectively) using the total and concentrated apoplastic fluid as detection reagent against serial dilutions of crude plant extracts from RBD-producing plants, showing that this simple antibody preparation can be directly employed in detection procedures without the need of additional purification steps. cache = ./cache/cord-331786-wgt7kg6f.txt txt = ./txt/cord-331786-wgt7kg6f.txt === reduce.pl bib === id = cord-329855-pr7g6ivu author = Kalfaoglu, Bahire title = T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis date = 2020-05-30 pages = extension = .txt mime = text/plain words = 5344 sentences = 301 flesch = 50 summary = By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of the transcription factor FOXP3 and interestingly, both the differentiation of regulatory T-cells (Tregs) and Th17 was inhibited. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, while activated CD4+ T-cells continue to promote further viral infection through the production of Furin. These CD25 + activated T-cells are likely to be short-lived and do not initiate FOXP3 transcription in severe COVID-19 patients, while they can differentiate into Tregs in moderate infections. These collectively support that FURIN expression is induced in highly activated non-regulatory CD25 + CD4 + T-cells in severe COVIDOur study has shown that CD4 + T-cells in severe COVID-19 patients have dysregulated activation and differentiation mechanisms. cache = ./cache/cord-329855-pr7g6ivu.txt txt = ./txt/cord-329855-pr7g6ivu.txt === reduce.pl bib === id = cord-333703-1ku3jc9s author = Kraus, Aurora title = A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date = 2020-11-08 pages = extension = .txt mime = text/plain words = 8452 sentences = 605 flesch = 57 summary = Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. In mice and humans, ace2 expression is detected in 121 sustentacular cells, olfactory stem cells known as horizontal and globose basal cells in the 122 olfactory epithelium, and vascular cells (pericytes) in the olfactory bulb (Brann et al., 2020 The present study reports for the first time that zebrafish larvae exposed to SARS-CoV-2 appear 134 to mount innate immune responses that resemble cytokine responses of mild COVID-19 patients. There are copious amounts of immune cells in the teleost olfactory organ ( Intranasal delivery of SARS-CoV-2 S RBD induces inflammatory responses and 318 widespread loss of olfactory receptor expression in adult zebrafish olfactory organ 319 320 cache = ./cache/cord-333703-1ku3jc9s.txt txt = ./txt/cord-333703-1ku3jc9s.txt === reduce.pl bib === id = cord-328659-miujzgtd author = Mishra, Akhilesh title = Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions date = 2020-07-27 pages = extension = .txt mime = text/plain words = 6064 sentences = 361 flesch = 55 summary = title: Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. The rapid global spread of SARS-CoV-2 in a short period of time and the availability of a large number of fully sequenced genomes provide us with a unique opportunity of understanding the short-term temporal evolution of this virus in humans in a near real-time scale. By this approach we propose the classification of the SARS-CoV-2 virus genomes into 5 mutually exclusive lineages with unique set of co-occurring mutations and geographic distribution. Our analysis revealed a total of 40 nucleotide substitutions which occurred at > 1% in the SARS-CoV-2 genomes (Table 1 and Figure 1A ). We consider a specific mutation or a set of cooccurring mutations as "lineage-defining" for SARS-CoV-2, only when they are present in at least 2% (n=30) of the sequences analysed. cache = ./cache/cord-328659-miujzgtd.txt txt = ./txt/cord-328659-miujzgtd.txt === reduce.pl bib === id = cord-334313-v2syspu6 author = Long, S. Wesley title = Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date = 2020-05-03 pages = extension = .txt mime = text/plain words = 4525 sentences = 251 flesch = 48 summary = We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. Because in vitro resistance of SARS-CoV to remdesivir has been reported to be caused by either of two amino acid replacements in RdRp (Phe476Leu and Val553Leu), we interrogated our data for polymorphisms in the nsp12 gene. cache = ./cache/cord-334313-v2syspu6.txt txt = ./txt/cord-334313-v2syspu6.txt === reduce.pl bib === id = cord-332539-v1bfm57x author = Gohl, Daryl M. title = A Rapid, Cost-Effective Tailed Amplicon Method for Sequencing SARS-CoV-2 date = 2020-05-11 pages = extension = .txt mime = text/plain words = 5048 sentences = 246 flesch = 55 summary = Several variants of the ARTIC protocol exist in which the pooled SARS-CoV-2 amplicons from a sample are taken through a NGS library preparation protocol (using either ligation or tagmentation-based approaches) in which sample-specific barcodes are added, and are then sequenced using either short-read (Illumina) or long-read (Oxford Nanopore, PacBio) technologies. We sequenced these samples using Illumina's Nextera DNA Flex Enrichment protocol using a respiratory virus oligo panel containing probes for SARS-CoV-2, the ARTIC v3 tiled primers, and a novel tailed amplicon method designed to reduce cost and streamline the preparation of SARS-CoV-2 sequencing libraries. For the Illumina DNA Flex Enrichment protocol, SARS-CoV-2 genome coverage was more complete for samples with lower N1 and N2 Cts (ranging from ~20-30) at comparable read depths and coverage thresholds than with amplicon approaches, similar to the BEI WA isolate data ( Figure 3C , Supplemental Figure S2 -S3). cache = ./cache/cord-332539-v1bfm57x.txt txt = ./txt/cord-332539-v1bfm57x.txt === reduce.pl bib === id = cord-335118-oa9jfots author = Taka, E. title = Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor date = 2020-09-21 pages = extension = .txt mime = text/plain words = 5264 sentences = 344 flesch = 61 summary = By performing all-atom Molecular Dynamics (MD) simulations, we identified an extended network of salt bridges, hydrophobic and electrostatic interactions, and hydrogen bonding between the receptor-binding domain (RBD) of the S protein and ACE2. Initial studies have constructed a homology model of SARS-CoV-2 RBD in complex with ACE2, based on the SARS-CoV crystal structure (8, 14) and performed conventional MD (cMD) simulations totaling 10 ns (15, 16) and 100 ns (17, 18) in length to estimate binding free energies (15, 16) and interaction scores (18) . In this study, we performed a comprehensive set of all-atom MD simulations totaling 16.5 µs in length using the recently-solved structure of the RBD of the SARS-CoV-2 S protein in complex with the PD of ACE2 (7) . In 20 SMD simulations (each 15 ns, totaling 300 ns in length, table S1), the average work applied to unbind RBD from PD was 71.1 ± 12.7 kcal/mol (mean ± s.d.), demonstrating that the S protein binds stably to ACE2 (Fig. 3B) . cache = ./cache/cord-335118-oa9jfots.txt txt = ./txt/cord-335118-oa9jfots.txt === reduce.pl bib === id = cord-334624-chnibsa1 author = Hayn, Manuel title = Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date = 2020-10-30 pages = extension = .txt mime = text/plain words = 5355 sentences = 432 flesch = 57 summary = Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation. SARS-CoV-1 ORF6 is about 4-fold less potent in antagonizing type I IFN signaling (Fig. 243 4b) but induces higher levels of autophagy (Fig. 4c) . Examination of the functional conservation showed that SARS-CoV-2 Nsp15 was less 319 efficient in blocking innate immune activation, both type I IFN induction and signaling, than SARS-320 Hepatitis C virus viruses to block anti-viral autophagic turnover 50 and thus may represent a common studies will see more mechanistic data to explain the molecular details of the impact of SARS-CoV-2 343 proteins on innate immune activation. cache = ./cache/cord-334624-chnibsa1.txt txt = ./txt/cord-334624-chnibsa1.txt === reduce.pl bib === id = cord-334220-sqvfr31q author = Messina, Francesco title = Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date = 2020-11-03 pages = extension = .txt mime = text/plain words = 4218 sentences = 237 flesch = 44 summary = The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. cache = ./cache/cord-334220-sqvfr31q.txt txt = ./txt/cord-334220-sqvfr31q.txt === reduce.pl bib === id = cord-334300-hnrmaytm author = Ventura Fernandes, Bianca H title = Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction date = 2020-10-20 pages = extension = .txt mime = text/plain words = 1799 sentences = 126 flesch = 50 summary = Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus. 169 In the global task to develop the vaccine and possible therapeutic approaches for 170 COVID-19, several animal models have been proposed, such as mice 10 , hACE2 171 transgenic mice 11 , alpaca 12 , golden Syrian hamsters, ferrets, dogs, pigs, chickens, and 172 cats 9 , and species of non-human primates 10 . cache = ./cache/cord-334300-hnrmaytm.txt txt = ./txt/cord-334300-hnrmaytm.txt === reduce.pl bib === id = cord-336012-8klkojpo author = Harilal, Divinlal title = SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission date = 2020-06-18 pages = extension = .txt mime = text/plain words = 3040 sentences = 144 flesch = 45 summary = Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic. Here we show that cWGS is cost-effective and is highly scalable when using a target enrichment sequencing method, and we also demonstrate its utility in tracking the origin of SARS-CoV-2 transmission. cache = ./cache/cord-336012-8klkojpo.txt txt = ./txt/cord-336012-8klkojpo.txt === reduce.pl bib === id = cord-336343-qbcb9qi3 author = Agarwal, Ajay title = in-silica Analysis of SARS-CoV-2 viral strain using Reverse Vaccinology Approach: A Case Study for USA date = 2020-06-16 pages = extension = .txt mime = text/plain words = 2332 sentences = 154 flesch = 56 summary = Using in-silica analysis and reverse vaccinology, two leader proteins were identified to be potential vaccine candidates for development of a multi-epitope drug. This study aims to utilize a reverse-vaccinology approach in order to identify potential vaccine candidates for COVID19 for the country USA. For MHC Class-I T-cell epitope prediction for ORF1ab leader proteins, NetMHCpan EL 4.0 method was used. The T-cell epitopes of the MHC Class-I for both the leader protein were determined using the NetMHCpan EL 4.0 prediction method of the IEDB server keeping the sequence length at 9. For MHC class-II, T-cell epitopes (HLA DRB1*04-01 allele) of the proteins were also determined using the IEDB Analysis tools. The potential T-cell epitopes, whose topology, antigenicity, allergenicity, toxicity and conservancy was analysed, for ORF1ab leader proteins MT326102 and MT326175 are depicted in the following tables. Out of the two MHC Class-I epitopes selected for leader proteins ORF1ab MT326102 and MT326175, the global energy was lowest for LSLPVLQVR. cache = ./cache/cord-336343-qbcb9qi3.txt txt = ./txt/cord-336343-qbcb9qi3.txt === reduce.pl bib === id = cord-332374-cbiw6yvb author = Israeli, Ofir title = Evaluating the efficacy of RT-qPCR SARS-CoV-2 direct approaches in comparison to RNA extraction date = 2020-06-10 pages = extension = .txt mime = text/plain words = 1051 sentences = 77 flesch = 55 summary = Very recently, two studies [6] [7] used a direct no-buffer RT-qPCR approach which identified > 90% of the tested clinical samples. In this study, we tested the diagnostic efficiency following thermal inactivation (65°C for 30min and 95°C for 10min) without addition of lysis buffers ("no buffer") or following lysis by three buffers (Virotype, QuickExtract and 2% Triton-X-100) and compared it to diagnosis after standard RNA extraction. Samples included buffers spiked with SARS-CoV-2, at concentrations 0.1-100,000 PFU/ml and 30 clinical samples, previously diagnosed as positive (20) and negative (10). The limit of detection was 1 PFU/ml: In this concentration samples in the no buffer mode and Virotype at 95°C were not detected, while the RNA extraction mode averaged the lowest critical threshold ( Ct=29.8) followed by QuickExtract and Triton. SARS-CoV-2 detection by direct rRT-PCR without RNA extraction. Direct RT-qPCR detection of SARS-CoV-2 RNA from patient nasopharyngeal swabs without an RNA extraction step cache = ./cache/cord-332374-cbiw6yvb.txt txt = ./txt/cord-332374-cbiw6yvb.txt === reduce.pl bib === id = cord-331888-lbtuvdv3 author = de Souza, Dalton Garcia Borges title = Forecasting COVID-19 cases at the Amazon region: a comparison of classical and machine learning models date = 2020-10-09 pages = extension = .txt mime = text/plain words = 2434 sentences = 178 flesch = 61 summary = title: Forecasting COVID-19 cases at the Amazon region: a comparison of classical and machine learning models We compare the models autoregressive integrated moving average (ARIMA), Holt-Winters, support vector regression (SVR), k-nearest neighbors regressor (KNN), random trees regressor (RTR), seasonal linear regression with change-points (Prophet), and simple logistic regression (SLR). We evaluate the models according to their capacity to forecast in different historical scenarios of the COVID-19 progression, such as exponential increases, sudden decreases, and stability periods of daily cases. Holt-Winters, support vector regression (SVR), k-nearest neighbors regressor (KNN), 43 random trees regressor (RT), seasonal linear regression with change-points (SLiR) and 44 simple logistic regression (SLR), which dictates the baseline performance in this study. Thus, in this paper, we compared classical and machine learning models to forecast 231 the evolution of COVID-19 in the state. Application of ARIMA and Holt-Winters forecasting model to predict 294 the spreading of COVID-19 for India and its states cache = ./cache/cord-331888-lbtuvdv3.txt txt = ./txt/cord-331888-lbtuvdv3.txt === reduce.pl bib === id = cord-333089-ufyzqgqk author = Aguilar-Pineda, Jorge Alberto title = Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date = 2020-07-29 pages = extension = .txt mime = text/plain words = 6957 sentences = 359 flesch = 51 summary = Based on the structural complementarity and steric impediments between the S protein and human ACE2 (hACE2) protein membranes, we mapped the glycosylation sites of both models [21] [22] [23] [24] and performed molecular dynamics simulations (MDS) by 250 ns to stabilize the glycosylated SARS-CoV2 spike (S) and hACE2 complex (suppl. Given the possibility that occupancy at glycosylated residues or S-RBD binding sites by estrogens could modify the affinity of the SARS-CoV2 virus and alter entry into the cell thereby reducing infectivity, we sought to further examine these interactions using a range of complementary experimental approaches (see Table S1 ). In an effort to explore the potential protective effects of female sex hormones against SARS-CoV-2 infection, we examined the impact of estradiol (17β-diol) and a dietary-derived phytoestrogen (S-equol) on hACE2 structure and protein expression by a combination of in silico modeling, in vitro, and in vivo analysis. cache = ./cache/cord-333089-ufyzqgqk.txt txt = ./txt/cord-333089-ufyzqgqk.txt === reduce.pl bib === id = cord-335652-v98gv5uf author = Salazar, Cecilia title = Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date = 2020-05-10 pages = extension = .txt mime = text/plain words = 2063 sentences = 131 flesch = 48 summary = Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. This global health emergency has deployed international efforts to apply genomic epidemiology to track the spread of SARS-CoV-2 in real time. The recent development of targeted sequencing protocols by the ARTIC Network [3] , open sharing of genomic data through the GISAID (www.gisaid.org) database and straightforward bioinformatic tools for viral phylogenomics [4] , provides the opportunity to reconstruct global spatio-temporal dynamics of the COVID-19 pandemic with unprecedented comprehensiveness and resolution. We therefore aimed to characterize the spatio-temporal dynamics of SARS-CoV-2 by sequencing around 10% of cases occurred during the first week of outbreak in Montevideo, allowing us to identify transmission patterns, geographic origins and genetic variation among local strains. cache = ./cache/cord-335652-v98gv5uf.txt txt = ./txt/cord-335652-v98gv5uf.txt === reduce.pl bib === id = cord-334891-4jgtxg07 author = Choudhury, Abhigyan title = In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human date = 2020-11-11 pages = extension = .txt mime = text/plain words = 2926 sentences = 169 flesch = 54 summary = This study is hoped to rationalize the comparative binding and sensing of SARS-CoV-2 mRNA towards the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drive these reactions. Our in-silico study on the binding of all mRNAs with the intracellular TLRs shown that the mRNA of NSP10, S2, and E proteins of SARS-CoV-2 are potent enough to bind with TLR3, TLR9, and TLR7 and trigger downstream cascade reactions, and may be used as an option for validation of therapeutic option and immunomodulation against COVID-19. The binding of Spike protein with the human ACE2 receptor triggers the pathogenesis 3 of the SARS-CoV-2, leading to the activation of TLRs to activate the proliferation and 4 production of pro-inflammatory cytokines causing cytokine storm, those results in 5 inflammations. cache = ./cache/cord-334891-4jgtxg07.txt txt = ./txt/cord-334891-4jgtxg07.txt === reduce.pl bib === id = cord-334394-qgyzk7th author = Edgar, Robert C. title = Petabase-scale sequence alignment catalyses viral discovery date = 2020-08-10 pages = extension = .txt mime = text/plain words = 8134 sentences = 423 flesch = 51 summary = To address the ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 and expand the known sequence diversity of viruses, we aligned pangenomes for coronaviruses (CoV) and other viral families to 5.6 petabases of public sequencing data from 3.8 million biologically diverse samples. To expand the known repertoire of viruses and catalyse global virus discovery, in particular for Coronaviridae (CoV) family, we developed the Serratus cloud computing architecture for ultra-high throughput sequence alignment. We aligned 3,837,755 public RNA-seq, meta-genome, meta-virome and meta-transcriptome datasets (termed a sequencing run [5] ) against a collection of viral family pangenomes comprising all GenBank CoV records clustered at 99% identity plus all non-retroviral RefSeq records for vertebrate viruses (see Methods and Extended Table 1 ). We performed de novo assembly on 52,772 runs potentially containing CoV sequencing reads by combining 37,131 SRA accessions identified by the Serratus search with 18,584 identified by an ongoing cataloguing initiative of the SRA called STAT [5] . cache = ./cache/cord-334394-qgyzk7th.txt txt = ./txt/cord-334394-qgyzk7th.txt === reduce.pl bib === id = cord-331680-qlzhtxs0 author = Goryachev, A.N. title = Potential Opportunity of Antisense Therapy of COVID-19 on an in Vitro Model date = 2020-11-03 pages = extension = .txt mime = text/plain words = 4106 sentences = 200 flesch = 51 summary = In accordance with the purpose of the study, the following tasks were set: -to select the nucleotide sequence of the virus that is supposed to be inhibited, -to carry out the synthesis of oligonucleotide, -to determine cytotoxicity and antiviral activity in an in vitro experiment on cell culture. The assessment of antiviral activity of the drug in addition to cytopathic action was also taken into account by reducing the infectious titer of the virus in the culture of Vero cells E6 according to PCR RNA SARS-CoV-2, determined by the threshold of the number of reaction cycles (cycle treshold, Ct) in various dilutions of the study drug. Determination of the antiviral efficacy of the antisense oligonucleotide according to the treatment scheme (administration of the drug 24 hours after infection) was taken into account by the decrease in the infectious titer of the virus in the culture of Vero E6 cells by the cytopathic effect. cache = ./cache/cord-331680-qlzhtxs0.txt txt = ./txt/cord-331680-qlzhtxs0.txt === reduce.pl bib === id = cord-336628-0evl3wnd author = Neufeldt, Christopher J. title = SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB date = 2020-07-21 pages = extension = .txt mime = text/plain words = 5880 sentences = 362 flesch = 49 summary = Consistently, secreted cytokine profiles from both severe COVID-19 patients and SARS-CoV-2 infected lung epithelial cells, were enriched for pro-inflammatory cytokines and lacked type I/III IFNs. We also demonstrate that SARS-CoV-2 infection leads specifically to NF-κB but not IRF3 nuclear localization and that poly(I:C)-induced pathway activation is attenuated in infected cells. To confirm that the lack of IFN response in Calu-3 or A549-ACE2 cells infected with SARS-CoV-2 was not due to defects in the activation of innate immune pathways, we To test if IFNs could limit virus replication even after establishment of infection, A549-ACE2 cells were treated with high levels of various IFNs at the time point of infection or 6 h thereafter. these results indicate that SARS-CoV2-infection triggers the cGAS-STING pathway, leading to NF-κB-mediated induction of pro-inflammatory cytokines, and that this response can be controlled with STING inhibitors. cache = ./cache/cord-336628-0evl3wnd.txt txt = ./txt/cord-336628-0evl3wnd.txt === reduce.pl bib === id = cord-334584-xh41koro author = Dilucca, Maddalena title = Temporal evolution and adaptation of SARS-COV 2 codon usage date = 2020-05-29 pages = extension = .txt mime = text/plain words = 3955 sentences = 210 flesch = 56 summary = Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2'-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. An EN C plot analysis was performed to estimate the relative contributions of mutational bias and natural selection in shaping CUB of 13 genes encoding proteins that are crucial for SARS-CoV-2. For the funtionally important genes in each genome, we calculated the average values of CAI and ENC over time, as compared to the reference SARS-CoV-2 sequence (WSM). Based on the SiD combined with the CAI results ( Figure 5 ), we suggest that SARS-CoV-2, over time, has preferentially accumulated mutations in its genome which correspond to codons that adapt better to the human host. cache = ./cache/cord-334584-xh41koro.txt txt = ./txt/cord-334584-xh41koro.txt === reduce.pl bib === id = cord-332271-slouuryl author = Baker, Jeremy D. title = A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease date = 2020-08-27 pages = extension = .txt mime = text/plain words = 2683 sentences = 172 flesch = 52 summary = title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing 27 as selective and potent inhibitors of SARS-CoV-2 Mpro. Taken together this work suggests previous large-scale commercial 35 drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some 36 previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for 37 rapid repurposing. Taken together this work suggests previous large-scale commercial 35 drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some 36 previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for 37 rapid repurposing. Before screening the Broad library, 100 we piloted our assay conditions against the NIH Clinical collections library (~650 compounds) and 101 calculated our Z'-factor for each plate at 0.780 and 0.784 (Fig 1C and D) . cache = ./cache/cord-332271-slouuryl.txt txt = ./txt/cord-332271-slouuryl.txt === reduce.pl bib === id = cord-335443-iv2gs3kg author = Kim, Youngchang title = Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 date = 2020-06-28 pages = extension = .txt mime = text/plain words = 5464 sentences = 333 flesch = 57 summary = Here, we combine crystallography, biochemical and whole cell assays, and show that this compound inhibits SARS-CoV-2 Nsp15 and interacts with the uridine binding pocket of the enzyme's active site, providing basis for the uracil scaffold-based drug development. For SARS-CoV it was reported that Nsp15 cleaves highly conserved non-translated RNA on (+) sense strand showing that both RNA sequence and structure are important for cleavage 6, 7 . The enzyme cleaves efficiently eicosamer 5'GAACU¯CAU¯GGACCU¯U¯GGCAG3' at all four uridine sites (Fig. 1) , as well as synthetic EndoU substrate ( 5′-6-FAM-dArU¯dAdA -6-TAMRA-3′ ) 8 in the presence of Mn 2+ and the reaction rate increases with metal ion concentration. SARS-CoV-2 Nsp15 protein was crystallized with 5'UMP, 3'UMP, 5'GpU and Tipiracil using methods described previously 8 and the structures were determined at 1.82 Å, 1.85 Å, 1.97 Å and 1.85 Å, respectively. In the crystal structure of Nsp15/5'GpU, the dinucleoside monophosphate binds to the active site with uracil interacting with Tyr343 and Ser294 (Fig. 4B ), as seen in the Nsp15/5'UMP complex. cache = ./cache/cord-335443-iv2gs3kg.txt txt = ./txt/cord-335443-iv2gs3kg.txt === reduce.pl bib === id = cord-336793-9bbyu1qx author = Matsuyama, Shutoku title = The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells date = 2020-08-24 pages = extension = .txt mime = text/plain words = 709 sentences = 48 flesch = 62 summary = title: The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells We screened steroid compounds to obtain a drug expected to block host inflammatory responses and MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in non-structural protein 3 (nsp3) or nsp4. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients. In the present study, we found that an inhaled corticosteroid, ciclesonide suppresses replication of coronaviruses, including beta-coronaviruses (MHV-2, MERS-CoV, SARS-CoV, and SARS-CoV-2) and an alpha-coronavirus (HCoV-229E) in cultured cells. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral cache = ./cache/cord-336793-9bbyu1qx.txt txt = ./txt/cord-336793-9bbyu1qx.txt === reduce.pl bib === id = cord-336560-m5u6ryy9 author = Boudewijns, Robbert title = STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters date = 2020-07-02 pages = extension = .txt mime = text/plain words = 5019 sentences = 308 flesch = 51 summary = Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients. The lack of readily accessible serum markers or the absence of overt disease symptoms in hamsters prompted us to establish a non-invasive means to score for lung infection and SARS-CoV-2 induced lung disease by computed tomography (CT) as used in standard patient care to aid COVID-19 diagnosis with high sensitivity and monitor progression/recovery 7, 33, 35, 36 . Similar as in humans 37 , semiquantitative lung pathology scores were obtained from high-resolution chest micro-CT scans of freebreathing animals 38 The increase in replication of SARS-CoV-2 seen in IL28R-a -/hamsters, on one hand, combined with a tempered inflammatory response and lung injury as compared to WT hamsters, on the other hand, is in line with the role of type III IFN plays during respiratory virus infections, including SARS-CoV-1 53 . cache = ./cache/cord-336560-m5u6ryy9.txt txt = ./txt/cord-336560-m5u6ryy9.txt === reduce.pl bib === id = cord-338296-2hk7h132 author = Malla, Tek Narsingh title = Ebselen Reacts with SARS Coronavirus-2 Main Protease Crystals date = 2020-08-23 pages = extension = .txt mime = text/plain words = 490 sentences = 47 flesch = 71 summary = title: Ebselen Reacts with SARS Coronavirus-2 Main Protease Crystals The SARS coronavirus 2 main protease 3CLpro tailor cuts various essential virus proteins out of long poly-protein translated from the virus RNA. Any compound that inhibits the 3CLpro is therefore a potential drug to end the pandemic. Here we show that the diffraction power of 3CLpro crystals is effectively destroyed by Ebselen. Apart from the fragments, the most promising compounds are the α-ketoamides (Fig. 1) 24 which bind tightly to the 3CLpro 1-3 . SARS CoV-2 3CLpro in its functional, dimeric form 1 . expensive, but also less known compound that binds to the 3CLpro is Ebselen 4 . Ebselen has been shown 29 to bind strongly to the CoV-2 3CLpro 4 , but the structure of the complex is unknown. show what happens when Ebselen is added to 3CLpro crystals. Accordingly, the structure of only the untreated 3CLpro can be solved. cache = ./cache/cord-338296-2hk7h132.txt txt = ./txt/cord-338296-2hk7h132.txt === reduce.pl bib === id = cord-339720-d1stzy8w author = Zhao, Yuan title = Susceptibility of tree shrew to SARS-CoV-2 infection date = 2020-04-30 pages = extension = .txt mime = text/plain words = 2572 sentences = 180 flesch = 58 summary = No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature (above 39° C) particular in female animals during infection. In three young tree shrews (TS26, TS27 and TS28), we could detect viral RNA from only lungs in TS26 and TS27, but not in any tissue from TS28, although these animal had higher number of viral genomic copy numbers at the earlier stage of SARS-CoV-2 infection. Although SARS-CoV-2 infection didn't cause severe disease in all three ages of tree shrews, viral replication and mild histopathological changes were still observed in this study. In conclusion, tree shrew is not as susceptible to SARS-CoV-2 infection as the reported animal models of COVID-19, though limited replication of SARS-CoV-2 and mild histopathology was detected and observed in some tissues. Young Old Adult 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Histopathological examination of affected tissues from SARS-CoV-2 infected tree shrews. cache = ./cache/cord-339720-d1stzy8w.txt txt = ./txt/cord-339720-d1stzy8w.txt === reduce.pl bib === id = cord-335075-6wo2o5pp author = Bangaru, Sandhya title = Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate date = 2020-08-06 pages = extension = .txt mime = text/plain words = 4715 sentences = 240 flesch = 51 summary = Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Site-specific glycosylation of the SARS-CoV-2 prefusion spike protein produced in SF9 insect cells was analyzed using our recently described mass spectrometry proteomics-based method, involving treatment with proteases followed by sequential treatment with the endoglycosidases (Endo H and PNGase F) to introduce mass signatures in peptides with N-linked sequons (Asn-X-Thr/Ser) to assess the extent of glycosylation and the degree of glycan processing from high mannose/hybrid type to complex type (24) . In this study, we performed structural analysis of the Novavax SARS-CoV We also observed two non-spike densities within the spike trimer that corresponded with linoleic acid and polysorbate 80 detergent. cache = ./cache/cord-335075-6wo2o5pp.txt txt = ./txt/cord-335075-6wo2o5pp.txt === reduce.pl bib === id = cord-339012-4juhmjaj author = Hou, Wei title = Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date = 2020-07-28 pages = extension = .txt mime = text/plain words = 6756 sentences = 344 flesch = 48 summary = Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and "synaptic clefts" between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The detected sets of differential expressed genes (DEGs) for PEDV and MRV were analyzed by gene set enrichment analysis (GSEA) using functional bioinformatic programs to retrieve biological processes (pathways and Gene Ontology terms [GO-term]) and associations with chemical compounds, including drugs. cache = ./cache/cord-339012-4juhmjaj.txt txt = ./txt/cord-339012-4juhmjaj.txt === reduce.pl bib === id = cord-336938-03366q9t author = Thacker, Vivek V title = Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model date = 2020-08-10 pages = extension = .txt mime = text/plain words = 2818 sentences = 169 flesch = 49 summary = title: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model A combination of qRT-PCR, RNAscope, immunofluorescence, and ELISA measurements are used to study the dynamics of viral replication and host responses to a low dose infection of SARS-CoV-2 delivered to the apical surface of the epithelial face maintained at an air-liquid interface. We therefore establish a human lung-on-chip model for SARS-CoV-2 infections, and probe the viral growth kinetics, cellular localization and responses to a low dose infection using qRT-PCR, ELISA, RNAscope, immunofluorescence and confocal imaging (Fig. 1J) . Nevertheless, total RNA extracted from the apical and vascular channels of an infected LoC without macrophages at 1 dpi revealed >10 4 genomes in both epithelial and endothelial cells (Fig. 2C ) and genome copy numbers exceeded those for cellular housekeeping gene RNAseP (Fig. 2D ). Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors cache = ./cache/cord-336938-03366q9t.txt txt = ./txt/cord-336938-03366q9t.txt === reduce.pl bib === id = cord-339772-q814d6l7 author = Pach, Szymon title = ACE2-Variants Indicate Potential SARS-CoV-2-Susceptibility in Animals: An Extensive Molecular Dynamics Study date = 2020-05-14 pages = extension = .txt mime = text/plain words = 3735 sentences = 229 flesch = 60 summary = To investigate the reason for the variable susceptibility observed in different species, we have developed molecular descriptors to efficiently analyze our dynamic simulation models of complexes between SARS-CoV-2 S and ACE2. Moreover, we compared ACE2 sequences from rodents (mouse, rat, hamster, and red squirrel) to sample additional binding pockets in the ACE2-RBD interface and predict susceptibility to SARS-CoV-2 of the red squirrel (Sciurus vulgaris). To compare three-dimensional binding interfaces of animal ACE2-RBD complexes, we developed homology models of dog, cat, ferret, hamster, mouse, rat, and red squirrel proteins. Both outlier residues are located on flexible loops of ACE2 distal to the S binding site and represent polymorphic mutations from glycine in human crystal structure to serine in homology models. Based on known susceptibility of animal species to SARS-CoV-2 and the comparison of MD trajectories, we were able to develop models for prediction of RBD binding to ACE2. cache = ./cache/cord-339772-q814d6l7.txt txt = ./txt/cord-339772-q814d6l7.txt === reduce.pl bib === id = cord-338055-2d6n4cve author = Hassan, Sk. Sarif title = A unique view of SARS-CoV-2 through the lens of ORF8 protein date = 2020-08-26 pages = extension = .txt mime = text/plain words = 5942 sentences = 322 flesch = 55 summary = In this present study, we identified the distinct mutations present across unique variants of the SARS-CoV-2 ORF8 and classified them according to their predicted effect on the host, i.e disease or neutral and the consequences on protein structural stability. The ORF8 sequences of SARS-CoV-2, Bat-CoV RaTG13 and Pangolin-CoV have almost the same positive and negative charged amino acids, therefore we can say that probably they have similar kind of electrostatic and hydrophobic interactions, 135 which also contribute to the functionality of the proteins. • QKV07730.1: The T11A mutation occurred as the second mutation in this sequence, which was predicted to be of disease-increasing type and the polarity was changed from hydrophilic to hydrophobic, hence the structure and 305 function of the protein are expected to differ. cache = ./cache/cord-338055-2d6n4cve.txt txt = ./txt/cord-338055-2d6n4cve.txt === reduce.pl bib === id = cord-338734-laeocs3j author = Lima, Amorce title = Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen date = 2020-06-30 pages = extension = .txt mime = text/plain words = 2533 sentences = 141 flesch = 61 summary = In silico analysis and clinical sample testing showed that the primesr/probes designed by the CDC were specific to the SARS-CoV-2 as they accurately detected all reactive samples with an assay LoD of 200 copies/ml. A 149 series of two-fold dilutions of SARS-CoV-2 strain USA_WA1/2020 RNA were spiked in pooled 150 sputum at concentrations of 800 copies/ml to 0.05 copy/ml in order to determine the limit of 151 detection (LoD) of the assay. On the other hand, the average Ct values difference between 235 samples run within 2 days between DiaSorin Simplexa Covid 19 Direct assay and the modified 236 CDC SARS-CoV-2 assay was -2.42, and -6.0 between samples run within 5 days. In this study, we validated a modified CDC SARS-CoV-2 assay and compared its 263 performance to two commercial automated sample-to-answer assays for the detection of SARS-264 The difference is even greater 286 in samples that were run 5 days after the routine testing on the modified CDC SARS-CoV-2 287 assay. cache = ./cache/cord-338734-laeocs3j.txt txt = ./txt/cord-338734-laeocs3j.txt === reduce.pl bib === id = cord-339431-kyr5lv15 author = Saçar Demirci, Müşerref Duygu title = Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection date = 2020-03-17 pages = extension = .txt mime = text/plain words = 2323 sentences = 163 flesch = 52 summary = In the case of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA – based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Although there are studies regarding to the viral replication and their interaction with host innate immune system, the role of miRNA-mediated RNA-silencing in SARS-CoV-2 infection has not been enlightened yet. In this study, SARS-CoV-2 genome was searched for miRNA-like sequences and potential host-virus interactions based on miRNA actions were analyzed. In our study, we have also identified possible miRNA like small RNAs from SARS-CoV-2 genome which target important human genes. cache = ./cache/cord-339431-kyr5lv15.txt txt = ./txt/cord-339431-kyr5lv15.txt === reduce.pl bib === id = cord-336522-y9nzsv95 author = Rosenke, Kyle title = Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino-oligomers date = 2020-09-30 pages = extension = .txt mime = text/plain words = 1723 sentences = 121 flesch = 54 summary = title: Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino-oligomers Cell viability was 33 evaluated with an ATP-based method and viral growth was measured with quantitative RT-PCR 34 and TCID50 infectivity assays. Results: PPMO designed to base-pair with sequence in the 5'-terminal region or the leader 36 transcription regulatory sequence-region of SARS-CoV-2 genomic RNA were highly 37 efficacious, reducing viral titers by up to 4-6 log10 in cell cultures at 48-72 hours post-infection, 38 in a non-toxic and dose-responsive manner. Results: PPMO designed to base-pair with sequence in the 5'-terminal region or the leader 36 transcription regulatory sequence-region of SARS-CoV-2 genomic RNA were highly 37 efficacious, reducing viral titers by up to 4-6 log10 in cell cultures at 48-72 hours post-infection, 38 in a non-toxic and dose-responsive manner. In this study, five PPMO were designed to target the 5' UTR 107 and first translation start site-region of SARS-CoV-2 positive sense genomic RNA ( Table 1) . cache = ./cache/cord-336522-y9nzsv95.txt txt = ./txt/cord-336522-y9nzsv95.txt === reduce.pl bib === id = cord-341768-k86gsfng author = Suresh, Voddu title = Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies date = 2020-06-29 pages = extension = .txt mime = text/plain words = 2541 sentences = 141 flesch = 45 summary = title: Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin□converting enzyme 2 (ACE2), a proven functional receptor for SARS-CoV-2 in different organs of the hamster. Certain earlier studies have shown expression of ACE2 transcripts or protein by lung epithelial cells [15] [16] [17] [18] , hence, just after the reports that ACE2 binds with SARS-CoV-2 spike (S) protein, the research and clinical communities assumed that high level of ACE2 expression in lung or other part of the respiratory tract might be a major driving factor in the pathogenesis of this respiratory virus. High expression of ACE2 in the kidney is believed to contribute to SARS-CoV-2 virus pathogenesis and disease severity 22 In our analysis, in addition to kidney and different parts of the gut, brain, liver, tongue are three other extra-pulmonary organs that showed ACE2 expression (Figure 1, 3 & 4) . cache = ./cache/cord-341768-k86gsfng.txt txt = ./txt/cord-341768-k86gsfng.txt === reduce.pl bib === id = cord-341502-jlzufa28 author = Lee, Sungyul title = The SARS-CoV-2 RNA interactome date = 2020-11-02 pages = extension = .txt mime = text/plain words = 5845 sentences = 362 flesch = 51 summary = The second pool of 275 oligos ("Probe II") covers the remaining region (21563:29872, NC_045512.2) which is shared by both the gRNA and sgRNAs. To first check whether our method specifically captures the viral RNP complexes, we compared the resulting purification from Vero cells infected with SARS-CoV-2 (BetaCoV/Korea/KCDC03/2020) at MOI 0.1 for 24 hours (Kim et al., 2020b ) by either Probe I or Probe II. In combination, we define these 109 proteins as the "SARS-CoV-2 RNA interactome." 37 host proteins such as CSDE1 (Unr), EIF4H, FUBP3, G3BP2, PABPC1, ZC3HAV1 were enriched in both the Probe I and Probe II RNP capture experiments on infected cells ( Figure 1F ), thus identifying a robust set of the "core SARS-CoV-2 RNA interactome." Gene ontology (GO) term enrichment analysis revealed that these host factors are involved in RNA stability control, mRNA function, and viral process ( Figure S1F ). To measure the impact of these host proteins on coronavirus RNAs, we conducted knockdown experiments and infected Calu-3 cells with SARS-CoV-2 ( Figure 5A and 5B). cache = ./cache/cord-341502-jlzufa28.txt txt = ./txt/cord-341502-jlzufa28.txt === reduce.pl bib === id = cord-340240-dk48pdqa author = Kuo, Tsun-Yung title = Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 date = 2020-08-11 pages = extension = .txt mime = text/plain words = 1240 sentences = 91 flesch = 53 summary = title: Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. In this study, we present data from preclinical studies aimed at developing a COVID-19 candidate subunit 84 vaccine using CHO cell-expressed SARS-CoV-2 S-2P antigen combined with various adjuvants. We have 85 shown that S-2P, when mixed with CpG 1018 and aluminum hydroxide adjuvants, was most effective in 86 inducing antibodies that neutralized pseudovirus and wild-type live virus while minimizing Th2-biased 87 responses with no vaccine-related adverse effects. Previous studies showed that the lung-infiltrating eosinophils were a common 308 indication of Th2-biased immune responses seen in animal models testing SARS-CoV vaccine candidates [22] . cache = ./cache/cord-340240-dk48pdqa.txt txt = ./txt/cord-340240-dk48pdqa.txt === reduce.pl bib === id = cord-337973-djqzgc1k author = Hao, Siyuan title = Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium date = 2020-08-28 pages = extension = .txt mime = text/plain words = 2624 sentences = 166 flesch = 54 summary = title: Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium We also identified that SARS-CoV-2 does not infect HAE from the basolateral side, and the dominant SARS-CoV-2 permissive epithelial cells are ciliated cells and goblet cells, whereas virus replication in basal cells and club cells was not detectable. Our observation that SARS-CoV-2 was unable to infect epithelial cells from the 299 basolateral side supports that the viral entry receptor ACE2 is polarly expressed at the apical 300 side 30, 31 . We 332 determined that 1 pfu of SARS-CoV-2 in Vero-E6 cells has a particle (viral genome copy) 333 number of 820, suggesting that a load of 2.46 x 10 5 particles is required to productively infect 1 334 cm 2 of the airway epithelium, which is much higher than the small DNA virus parvovirus human 335 bocavirus 1 (HBoV1) we studied 55 . cache = ./cache/cord-337973-djqzgc1k.txt txt = ./txt/cord-337973-djqzgc1k.txt === reduce.pl bib === id = cord-342010-5mkf67os author = Levasseur, Anthony title = Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients date = 2020-09-04 pages = extension = .txt mime = text/plain words = 5348 sentences = 975 flesch = 103 summary = title: Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients cord_uid: 5mkf67os The evolution and mutational events of the SARS-CoV-2 genomes are critical for controlling virulence, transmissibility, infectivity, severity of symptoms and mortality associated to this infectious disease. We collected and investigated 309 SARS-CoV-2 genomes from patients infected in France. Detailed genome cartography of all mutational events (SNPs, indels) was reported and correlated to clinical features of patients. A comparative analysis between our 309 SARS-CoV-2 genomes from French patients and the reference Wuhan coronavirus genome revealed 315 substitution mutations and six deletion events: ten were in 5'/3' UTR, 178 were nonsynonymous, 126 were synonymous and one generated a stop codon. Clinical outcomes of the 309 COVID-19-infected patients were investigated according to the mutational signatures of viral variants. Inclusion of the French cohort enabled us to identify 161 novel mutations never reported in SARS-CoV-2 genomes collected worldwide. cache = ./cache/cord-342010-5mkf67os.txt txt = ./txt/cord-342010-5mkf67os.txt === reduce.pl bib === id = cord-338543-q6cl5kjp author = Salguero, Francisco J. title = Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19 date = 2020-09-17 pages = extension = .txt mime = text/plain words = 1093 sentences = 59 flesch = 56 summary = Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques, resembling the mild clinical cases of COVID-19 in humans. In contrast to prior publications, in which rhesus are accepted to be the optimal study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of novel and repurposed interventions against SARS-CoV-2. Throat swabs from cynomolgus macaques contained 147 higher levels of viral RNA early in infection (one to three dpc) and remained ≥4.5 x 148 10 4 copies/ml for all animals between four and nine dpc. However viral RNA 159 levels above the LLOQ were detected at both three dpc and five dpc in cynomolgus 160 macaques in comparison to two dpc and three dpc in rhesus macaques ( Figure 2D ). cache = ./cache/cord-338543-q6cl5kjp.txt txt = ./txt/cord-338543-q6cl5kjp.txt === reduce.pl bib === id = cord-337701-56tmg38b author = Xiao, Yan title = Comparison of three TaqMan Real-Time Reverse Transcription-PCR assays in detecting SARS-CoV-2 date = 2020-07-06 pages = extension = .txt mime = text/plain words = 2122 sentences = 120 flesch = 57 summary = In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). No effect of the 152 co-existed other viral nucleic acids on the LOD and the linear detection range was 153 observed, although higher Ct values were generated than those of RNA transcript 154 alone as template in all of the three qRT-PCR assays. Although most of the evaluated 232 assays exhibited good sensitivity, specificity, reproducibility and wide linear detection 233 range, performance test with clinical specimens from suspected COVID-19 patients 234 suggested that the N gene assay in IPBCAMS assays and CCDC assays, and the ORF 235 1b gene assays in IPBCAMS assays were the preferred qRT-PCR assays for accurate 236 detection of SARS-CoV-2. cache = ./cache/cord-337701-56tmg38b.txt txt = ./txt/cord-337701-56tmg38b.txt === reduce.pl bib === id = cord-339665-nwwutduy author = Patel, Ami title = Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date = 2020-07-29 pages = extension = .txt mime = text/plain words = 5258 sentences = 286 flesch = 52 summary = Prior work with the related coronaviruses, SARS-CoV and MERS-CoV, delineated that the Spike protein of these viruses was an important target for development of neutralizing antibodies, and in animal viral challenges vaccine targeted immunity (reviewed in (Du et al., 2009; Roper and Rehm, 2009; Thanh Le et al., 2020) (Liu et al., 2018; Muthumani et al., 2015; van Doremalen et al., 2020a) . These memory titers were comparable to those observed in other reported protection studies in macaques performed at the acute phase of the vaccine-induced immune response (Gao et al., 2020; van Doremalen et al., 2020b; Yu et al., 2020) and those reported in the sera of convalescent patients (Ni et al., 2020; Robbiani et al., 2020) . Our study and other published reports show that DNA vaccination with candidates targeting the full-length SARS-CoV-2 spike protein likely increase the availability of T cell immunodominant epitopes leading to a broader and more potent immune response, compared to partial domains and truncated immunogens. cache = ./cache/cord-339665-nwwutduy.txt txt = ./txt/cord-339665-nwwutduy.txt === reduce.pl bib === id = cord-342942-1s32o9m8 author = Stamatakis, George title = Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases date = 2020-06-22 pages = extension = .txt mime = text/plain words = 4074 sentences = 209 flesch = 47 summary = Here, we analyzed the proteolytic processing of overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes that generate antigenic peptides, aminopeptidases ERAP1, ERAP2 and IRAP. In this study, we utilized a novel approach to analyze antigen trimming by intracellular aminopeptidases ERAP1, ERAP2 and IRAP, focusing on the largest antigen of SARS-CoV-2, namely S1 spike glycoprotein. To investigate the trimming of antigenic epitope precursors by intracellular aminopeptidases that generate antigenic peptides, we used a mixture of 315 synthetic peptides derived from the sequence of the SARS-CoV-2 S1 spike glycoprotein. Our analysis of the largest antigen of SARS-CoV-2, S1 spike glycoprotein, suggests that aminopeptidase trimming can be a significant filter that helps shape which peptides will be presented by HLA. cache = ./cache/cord-342942-1s32o9m8.txt txt = ./txt/cord-342942-1s32o9m8.txt === reduce.pl bib === id = cord-342657-od48cntc author = Klemm, Theresa title = Mechanism and inhibition of SARS-CoV-2 PLpro date = 2020-06-19 pages = extension = .txt mime = text/plain words = 1704 sentences = 110 flesch = 65 summary = More variability is seen in MERS PLpro, which binds to ubiquitin and 138 ISG15 CTD similarly through its ability to 'close' the Fingers subdomain 26 (see 139 discussion in Extended Data Fig. 4) . A 1536-well low-volume high-throughput assay previously used to identify inhibitors Together, our data suggests that a repurposing strategy using 3727 unique known 199 drugs towards SARS2 PLpro is unlikely to yield drug candidates, and highlights the 200 importance of a counterscreen in assessing the validity of hits coming from a screen 201 of known drugs before any conclusions on their therapeutic potential can be drawn. Since it had previously 237 been shown that these inhibitors are specific for PLpro over human DUBs 1 (also see 238 Figure 3b ) and since treatment with rac5c did not affect Lys48-linked polyubiquitin in 239 the absence of nsp3 expression (Extended Data Fig 8f) , the effect of rac5c on 240 Lys48-polyubiquitin is likely due to inhibition of nsp3/PLpro. cache = ./cache/cord-342657-od48cntc.txt txt = ./txt/cord-342657-od48cntc.txt === reduce.pl bib === id = cord-340432-vm6m0kb4 author = Srivastava, Sukrit title = Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide date = 2020-09-06 pages = extension = .txt mime = text/plain words = 2661 sentences = 199 flesch = 54 summary = title: Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide Methodology A novel reverse epitomics approach, "overlapping-epitope-clusters-to-patches" method is utilized to identify multiple antigenic regions from the SARS-CoV-2 proteome. Multi-Patch Vaccine designing to combat SARS-CoV-2 infection by reverse epitomics approach, "Overlapping-epitope-clusters-to-patches" method. In the present study, we have reported a novel method to design a 1170 vaccine against SARS-CoV-2 by utilizing multiple antigenic patches from the viral 1171 proteins. The designed MPVs from the antigenic patches of SARS-CoV-2 proteins 1182 have several advantages over to the subunit and multi-epitope based vaccines. Design of multi epitope-based peptide vaccine against E 1409 protein of human 2019-nCoV: An immunoinformatics approach Multi-epitope based peptide 1549 vaccine design against SARS-CoV-2 using its spike protein In silico approach for designing of a multi-epitope based 1587 vaccine against novel Coronavirus (SARS-COV-2) cache = ./cache/cord-340432-vm6m0kb4.txt txt = ./txt/cord-340432-vm6m0kb4.txt === reduce.pl bib === id = cord-342599-558yn6pu author = Rinchai, Darawan title = A modular framework for the development of targeted Covid-19 blood transcript profiling panels date = 2020-05-22 pages = extension = .txt mime = text/plain words = 5230 sentences = 298 flesch = 42 summary = Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. In this proof of principle study, we used the available transcript profiling data from two separate studies to select Covid-19 relevant sets of modules (8, 9) . One of these applications provides access to module-level transcript abundance profiles for available Covid-19 blood transcriptome profiling datasets. Despite large differences between the two studies in terms of design, range of clinical severity, technology platforms and module coverage, the combined overall changes (detected at a high-level perspective) are consistent with those observed in known acute infections, such as those caused by influenza, respiratory syncytial virus (RSV) or S. cache = ./cache/cord-342599-558yn6pu.txt txt = ./txt/cord-342599-558yn6pu.txt === reduce.pl bib === id = cord-343586-28ezisog author = Rocca, María Florencia title = A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs date = 2020-05-07 pages = extension = .txt mime = text/plain words = 1498 sentences = 78 flesch = 47 summary = title: A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms as an alternative fast tool for SARS-CoV-2 detection from nasopharyngeal swabs samples. According to our preliminary results, mass spectrometry-based methods combined with multivariate analysis showed an interesting potential as a complementary diagnostic tool and further steps should be focused on sample preparation protocols and the improvement of the technology applied. These preliminary results suggest that MALDI-TOF MS coupled with ClinProTools software represents an interesting alternative as a screening tool for diagnosis of SARS-CoV-2, especially because of the good performance and accuracy obtained with samples in which viral presence was not detected. cache = ./cache/cord-343586-28ezisog.txt txt = ./txt/cord-343586-28ezisog.txt === reduce.pl bib === id = cord-344909-0o55l4iy author = Cross, Robert W. title = Use of convalescent serum reduces severity of COVID-19 in nonhuman primates date = 2020-10-14 pages = extension = .txt mime = text/plain words = 5711 sentences = 291 flesch = 49 summary = However, and importantly, lower levels of SARS-CoV-2 in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several parameters associated with coagulation and inflammatory processes were observed in monkeys that received convalescent sera versus untreated controls. Differences in clinical parameters of the LD-treated group with untreated control animals from this study or historical control animals were minimal; however, the lack of infectious SARS-CoV-2 in the BAL samples from all of the LD-treated animals and reduced lung pathology suggest that an antiviral effect was present despite the lower concentration of neutralizing antibodies in the dose of convalescent sera administered. PRNT50 assays were performed on pooled convalescent sera from AGMs challenged with the homologous isolate of SARS-CoV-2 in previous studies (Cross et al., 2020; Woolsey et al., 2020) compared with control animals on day 2 post infection (d) and cache = ./cache/cord-344909-0o55l4iy.txt txt = ./txt/cord-344909-0o55l4iy.txt === reduce.pl bib === id = cord-342456-5gp3cry0 author = Hoagland, Daisy A. title = Modulating the transcriptional landscape of SARS-CoV-2 as an effective method for developing antiviral compounds date = 2020-07-13 pages = extension = .txt mime = text/plain words = 4511 sentences = 240 flesch = 48 summary = Utilizing expression patterns of SARS-CoV-2-infected cells, we identified a region in gene expression space that was unique to virus infection and inversely proportional to the transcriptional footprint of known compounds characterized in the Library of Integrated Network-based Cellular Signatures. These signatures were then used as queries against the LINCS L1000 dataset, a collection of gene expression profiles generated following the administration of >20,000 bioactive compounds including >1,000 FDA-approved drugs to human cell lines at a variety of different times and concentrations (Subramanian et al., 2017) With L1000FWD , we could identify reciprocal transcriptional signatures generated between SARS-CoV-2 infection and a given compound. Overall, based on the L1000 data, these seven compounds influence the same pharmacological high-dimensional gene expression signature space and are predicted to disrupt key cellular processes that are modulated in response to SARS-CoV-2 infection. cache = ./cache/cord-342456-5gp3cry0.txt txt = ./txt/cord-342456-5gp3cry0.txt === reduce.pl bib === id = cord-340516-9dfaqsv7 author = Moore, Anne C. title = Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date = 2020-09-06 pages = extension = .txt mime = text/plain words = 6679 sentences = 335 flesch = 48 summary = We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Here, we report the induction of neutralizing antibody (Nab), IgG and IgA antibody responses, and T cell responses in mice following immunization of rAd vectors expressing one or more SARS-CoV-2 antigens. We have previously demonstrated that an oral, tableted rAd-based vaccine can induce protection against respiratory infection and shedding following influenza virus challenge 15 as well as intestinal immunity to norovirus antigens in humans 12 . In summary, these studies in mice represent our first step in creating a vaccine candidate, demonstrating the immunogenicity of the construct at even low vaccine doses and the elucidation of the full-length spike protein as a leading candidate antigen to induce T cell responses and superior systemic and mucosal neutralizing antibody. cache = ./cache/cord-340516-9dfaqsv7.txt txt = ./txt/cord-340516-9dfaqsv7.txt === reduce.pl bib === id = cord-342015-bz2vab6e author = Ouadfeul, Sid-Ali title = Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date = 2020-08-16 pages = extension = .txt mime = text/plain words = 1386 sentences = 86 flesch = 58 summary = In this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Arneodo et al (1996) published a paper deals with the study of the Long-Range Correlation (LRC) character of DNA sequences using the 1D continuous wavelet transform method. Audit et al (2004) published a paper deals with wavelet Analysis of DNA bending profiles reveals structural constraints on the evolution of genomic sequences, Voss (1996) published a paper deals with the evolution of Long-Range fractal correlations and 1/f noise in DNA base sequences. In this paper the 1D Wavelet Transform Modulus Maxima Lines (WTMM) method is used to demonstrate the monofractal behavior of SARS-CoV-2 RNA sequences downloaded from the NCBI database and to estimate the so-called Hurst exponent, the goal is to investigate the LRC character in these sequences. cache = ./cache/cord-342015-bz2vab6e.txt txt = ./txt/cord-342015-bz2vab6e.txt === reduce.pl bib === id = cord-340291-bah2ege0 author = Kohmer, Niko title = Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity date = 2020-05-10 pages = extension = .txt mime = text/plain words = 1001 sentences = 63 flesch = 55 summary = With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. With exception of one sample, all positive tested samples in the analysed cohort, using the 37 commercially available assays examined (including the in-house developed IFA), demonstrated 38 neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-39 there is an increasing demand in the detection of antibodies -especially of IgG antibodies. Currently there are many S 57 protein based commercially or in-house developed assays available, but there is limited data on how 58 these tests perform with clinical samples and if the detected IgG antibodies provide protective 59 cache = ./cache/cord-340291-bah2ege0.txt txt = ./txt/cord-340291-bah2ege0.txt === reduce.pl bib === id = cord-343027-ks3fn9pq author = Fraser, Nicholas title = Preprinting the COVID-19 pandemic date = 2020-09-18 pages = extension = .txt mime = text/plain words = 5707 sentences = 324 flesch = 56 summary = When the data was broken down by server, it 132 was evident that whilst posting of COVID-19 preprints to bioRxiv had remained relatively steady, 133 preprints posted to medRxiv increased with time (Supplemental Fig. 2A) . Server usage differences were more pronounced 237 for COVID-19 preprints; multiple post-hoc comparisons confirmed that bioRxiv and medRxiv received 238 significantly higher usage per COVID-19 preprint than all other servers for which data was available 239 (Tukey HSD; all p values < 0.001). However, for non COVID-19 preprints, the only observed pairwise 240 differences between servers indicated greater bioRxiv usage than SSRN or Research Square (Tukey 241 HSD; all p values < 0.001). We also compared rates of PDF downloads for bioRxiv and medRxiv preprints 506 with a number of other preprint servers (Preprints.org, SSRN, and Research Square) (Supplemental Counts of multiple altmetric indicators (mentions in tweets, blogs, and news articles) were retrieved 510 via Altmetric (https://www.altmetric.com), a service that monitors and aggregates mentions to 511 scientific articles on various online platforms. cache = ./cache/cord-343027-ks3fn9pq.txt txt = ./txt/cord-343027-ks3fn9pq.txt === reduce.pl bib === id = cord-346299-2s9j01q7 author = Salim Khan, S Muhammad title = Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study date = 2020-09-04 pages = extension = .txt mime = text/plain words = 1407 sentences = 102 flesch = 55 summary = title: Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study Background Prevalence of IgG antibodies against SARS-CoV-2 infection provides essential information for deciding disease prevention and mitigation measures. We estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar. 65 Besides, assuming that antibodies provide partial or total immunity, seroprevalence surveys give Here, we present the results of a cross-sectional seroprevalence study in District Srinagar, 70 conducted between 1 st and 15 th July 2020, to estimate the prevalence of IgG antibodies against 71 SARS-CoV-2 among adults using a sensitive and specific chemiluminescent microparticle 72 immunoassay (CMIA)-based test. 156 We estimated the number of infections till two weeks before the study period, i.e., 15 th June 2020 157 to 30 th June 2020, by applying the age-and gender-specific seroprevalence rates found in the Table) . cache = ./cache/cord-346299-2s9j01q7.txt txt = ./txt/cord-346299-2s9j01q7.txt === reduce.pl bib === id = cord-343317-97n1j0jj author = Duan, Xiaohua title = Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date = 2020-05-02 pages = extension = .txt mime = text/plain words = 3776 sentences = 222 flesch = 56 summary = Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. The organoids infected with SARS-CoV-2 pseudo-entry virus at MOI=0.01 showed a strong signal at 24 hpi (Fig. 2a) . The mRNAs of SARS-CoV-2 pseudo-entry virus, including VSV-NS, VSV-N, and VSV-M, were detected in all five cell populations (Fig. 2f) , but not in the uninfected COs (Extended Data Fig. 2f) . Immunohistochemistry detected luciferase in ACE2 + and Villin + cells, suggesting these are permissive to SARS-CoV-2 pseudo-entry virus infection in vivo (Fig. 2k) . Next, we adapted hPSC-COs to a high throughput screening platform and probed the Prestwick FDA-approved drug library to identify drug candidates capable of blocking SARS-CoV-2 pseudo-virus infection. cache = ./cache/cord-343317-97n1j0jj.txt txt = ./txt/cord-343317-97n1j0jj.txt === reduce.pl bib === id = cord-333420-qqyg9um9 author = Zhu, Xun title = idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates date = 2020-10-09 pages = extension = .txt mime = text/plain words = 460 sentences = 35 flesch = 58 summary = title: idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates idCOV is a phylogenetic pipeline for quickly identifying the clades of SARS-CoV-2 virus isolates from raw sequencing data based on a selected clade-defining marker list. Using a public dataset, we show that idCOV can make equivalent calls as annotated by Nextstrain.org on all three common clade systems using user uploaded FastQ files directly. The on-going Coronavirus disease 2019 (Covid-19) pandemic has resulted in over 734,000 deaths, affect-20 ing more than 188 countries and territories (CSSE, 2020; Dong, et al., 2020) . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously known as 2019-nCoV) 23 is the pathogenic cause of Covid-19 (Lescure, et al., 2020) . In order to quickly identify the clade of an isolate of SARS-Cov-2 given its sequencing FastQ files, 30 we have developed a bioinformatics pipeline and a user-friendly web interface. cache = ./cache/cord-333420-qqyg9um9.txt txt = ./txt/cord-333420-qqyg9um9.txt === reduce.pl bib === id = cord-344236-qp3ianzf author = Ali, Fedaa title = ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity date = 2020-05-08 pages = extension = .txt mime = text/plain words = 2465 sentences = 163 flesch = 54 summary = Classical electrostatic calculations based on solving Poisson-Boltzmann (PB) equation is used to investigate the interaction energies between SARS-CoV-2 and ACE2 for different mutated ACE2 structures. In an attempt to better understand the susceptibility of different populations to infection by SARS-CoV-2, we gathered data on ACE2 missense variants from different projects and databases that aggregate allele frequencies (AF). These projects and databases included Single Nucleotide Polymorphism Database (dbSNP) 12, 13 , 1000 genomes project phase 3 (1KGP3) 14 , Allele Frequency Aggregator (ALFA project) a , Exome Aggregation Consortium (ExAC) 15 SARS-CoV-2 was reported to bind to human ACE2 via different ACE2 residues; Q24, D30, H34, Y41, Q42, M82, K353 and R357 5 . The electrostatic and the van der Waal contribution to the interaction energies of SARS-CoV-2/ACE2 were compared between single mutated and WT protein at pH =7 (Table 1 ). cache = ./cache/cord-344236-qp3ianzf.txt txt = ./txt/cord-344236-qp3ianzf.txt === reduce.pl bib === id = cord-345299-4k7qymqd author = Xiong, Hua-Long title = Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro date = 2020-06-05 pages = extension = .txt mime = text/plain words = 1471 sentences = 88 flesch = 47 summary = To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. In this study, the anti-SARS-Cov-2 potentiality of 1403 FDA approved drugs were quantitatively evaluated by the pseudovirus-based assay. In the second round of screening, inhibition of VSV-SARS-CoV-2-Sdel18 virus infection and cell cytotoxicity were both detected (Supplementary Figure 1) . The robust assay based on VSV-SARS-CoV-2-Sdel18 pseudovirus screened out the potential drugs with high efficiency, then the inhibitory effect was confirmed by authentic SARS-CoV-2 assay. The relative value or inhibition rate of candidate drugs were calculated according to the decrease of GFP positive cell number (for pseudovirus-based assay) or cytopathic effect (for authentic SARS-CoV-2-based assay). cache = ./cache/cord-345299-4k7qymqd.txt txt = ./txt/cord-345299-4k7qymqd.txt === reduce.pl bib === id = cord-345405-ngpsgn63 author = Tremiliosi, Guilherme C. title = Ag nanoparticles-based antimicrobial polycotton fabrics to prevent the transmission and spread of SARS-CoV-2 date = 2020-06-26 pages = extension = .txt mime = text/plain words = 6259 sentences = 339 flesch = 46 summary = An adaptation of ISO 18184 Determination of antiviral activity of textile products Standard Method [23] was used as a reference for a quantitative method to evaluate the treated polycotton's ability to inactivate the SARS-CoV-2 virus particles (SARS-CoV-2/human/BRA/SP02cc/2020 -MT350282), under the tested conditions, at two different time intervals (2 and 5 minutes of contact time). The antiviral activity test was designed to determine the inactivation of viral particles upon short exposure to the products, which in this case were the Ag-based treated polycotton samples incubated in liquid media. Table 6 shows the number of copies of the control media without any fabric sample, non-treated polycotton, and the two Ag-based treated polycotton samples at the two different tested time periods. Application of silver nanoparticles to cotton fabric as an antibacterial textile finish Fibers Polym Antibacterial properties of cotton fabric treated with silver nanoparticles cache = ./cache/cord-345405-ngpsgn63.txt txt = ./txt/cord-345405-ngpsgn63.txt === reduce.pl bib === id = cord-345499-hq5um68k author = Xiong, Rui title = Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 date = 2020-03-12 pages = extension = .txt mime = text/plain words = 5275 sentences = 317 flesch = 53 summary = title: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. We identified that targeting DHODH offers broad-spectrum antiviral efficacies against various RNA viruses, including the DAA-resistant influenza virus and the newly emerged coronavirus SARS-CoV-2. cache = ./cache/cord-345499-hq5um68k.txt txt = ./txt/cord-345499-hq5um68k.txt === reduce.pl bib === id = cord-343476-0chuwvg6 author = MacLean, Oscar A. title = Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans date = 2020-05-29 pages = extension = .txt mime = text/plain words = 1386 sentences = 73 flesch = 51 summary = Here we contrast the role of positive selection and recombination in the Sarbecoviruses in horseshoe bats to SARS-CoV-2 evolution in humans. While methods can detect some evidence for positive selection in SARS-CoV-2, we demonstrate these are mostly due to recombination and sequencing artefacts. For all but two of the ten positive selected codons, this signal was being driven by apparent convergent evolution (or homoplasy) in the tree, with the same mutation occurring in parallel across the phylogeny. To investigate whether this observation was truly due to independent events or because of recombination signatures in the SARS-CoV-2 outbreak tree, we firstly determined if the samples with these convergent mutations were geographically correlated. The Spike V367F signal was driven by apparent convergent evolution between four french samples sequenced in January and a Hong Kong sample 412028, which shows shared variation either side of the homoplasy suggesting it is not a recombinant (Supplementary figure 3C) . cache = ./cache/cord-343476-0chuwvg6.txt txt = ./txt/cord-343476-0chuwvg6.txt === reduce.pl bib === id = cord-347441-8ow952d8 author = Parvez, Md Sorwer Alam title = Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism date = 2020-06-07 pages = extension = .txt mime = text/plain words = 1027 sentences = 75 flesch = 62 summary = title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh. As many of the Bangladeshi people return during the COVID-19 39 outbreak mainly from China, India, Saudi Arabia, Spain, Italy, Japan, Qatar, Canada, Kuwait, USA, 40 France, Sweden, and Switzerland, the first deposited genome sequence of those countries were also 41 retrieved. In total, three models were generated using the template PDB ID: 6VSB; one model for the spike protein 118 of reference strain, and the two others were for two different mutant isolates from Bangladesh (Fig 3) . cache = ./cache/cord-347441-8ow952d8.txt txt = ./txt/cord-347441-8ow952d8.txt === reduce.pl bib === id = cord-344560-662pfa61 author = Yamamoto, Norio title = Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro date = 2020-04-08 pages = extension = .txt mime = text/plain words = 1419 sentences = 96 flesch = 71 summary = After the outbreak of severe acute respiratory syndrome (SARS) in 2003, screening of approved drugs identified at least two human immunodeficiency virus type-1 (HIV-1) protease inhibitors, lopinavir and nelfinavir, as compounds that inhibited SARS-CoV replication in vitro 3, 4 . Among these inhibitors tested, the high concentrations of drugs were required to inhibit SARS-CoV-2 replication in amprenavir (EC 50 = 31.32 µM, CC 50 > 81 µM, SI > 2.59), darunavir (EC 50 = 46.41 µM, CC 50 > 81 µM, SI > 1.75), and indinavir (EC 50 = 59.14 µM CC 50 > 81 µM, SI > 1.37) (Fig. 1g , h, i, j). Lopinavir, which has been clinically tested in patients with SARS and COVID-19, blocked SARS-CoV-2 replication at a low concentration range and its SI was relatively high among nine inhibitors (EC 50 = 5.73 µM, CC 50 = 74.44 µM, SI = 12.99) (Fig. 1b, j) . These results suggest that nelfinavir, lopinavir, and tipranavir can achieve EC 50 of each drug in human and are effective in the treatment of COVID-19 patients. cache = ./cache/cord-344560-662pfa61.txt txt = ./txt/cord-344560-662pfa61.txt === reduce.pl bib === id = cord-343517-vf32wxkx author = Lokman, Syed Mohammad title = Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date = 2020-04-11 pages = extension = .txt mime = text/plain words = 2745 sentences = 163 flesch = 53 summary = However, SARS-CoV-2 has emerged with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. The evolutionary distances showed that all the SARS-CoV-2 spike proteins cluster in the same node of the phylogenetic tree confirming the sequences are similar to Refseq YP_009724390 (Fig. 2) . cache = ./cache/cord-343517-vf32wxkx.txt txt = ./txt/cord-343517-vf32wxkx.txt === reduce.pl bib === id = cord-346335-el45v0a5 author = Tan, H.S. title = Fourier spectral density of the coronavirus genome date = 2020-08-11 pages = extension = .txt mime = text/plain words = 4646 sentences = 224 flesch = 56 summary = We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density. An example of a seminal paper in this subject is that of Voss in [2] where the author found that the spectral density of the genome of many different species follows a power law of the form 1/k β in the low-frequency domain, with the exponent β potentially related to the organism's evolutionary category. We develop a few models to characterize the typical spectrum, and in the process stumble upon a linear scaling law between a measure of the complexity of each genome and the power-law exponent that describes the enveloping curve of the low-frequency domain. cache = ./cache/cord-346335-el45v0a5.txt txt = ./txt/cord-346335-el45v0a5.txt === reduce.pl bib === id = cord-344949-9zyz4hll author = Luban, Jeremy title = The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines date = 2020-08-05 pages = extension = .txt mime = text/plain words = 5552 sentences = 277 flesch = 47 summary = a Selectivity index is the ratio of CC50 to EC50 b values are mean ± standard deviation (SD) Abbreviations: CC50, compound concentration at which cell number is reduced by 50%; EC50, compound concentration at which viral replication on a linear scale is inhibited by 50%; GFP, green fluorescent protein; HCV, hepatitis C virus replicon genotype 1b; PIV-3, Parainfluenza type 3; RSV, respiratory syncytial virus; RT-qPCR, quantitative reverse transcription PCR; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; TCID50, tissue culture infectious dose 50%. In the BT co-cell culture system, which models chronic inflammatory conditions driven by B cell activation and antibody production, incubation of cells with 10 nM PTC299 resulted in a significant reduction in the levels of soluble (s)IgG, sIL-17A, sIL-17F, sIL-6, and sTNFα released from the cells after 72 hours of stimulation (range, 49% to 68%) (all p values <0.01) ( Figure 4 and Table 2 ). cache = ./cache/cord-344949-9zyz4hll.txt txt = ./txt/cord-344949-9zyz4hll.txt === reduce.pl bib === id = cord-346670-34wfy52f author = Gobeil, Sophie M-C. title = D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction date = 2020-10-12 pages = extension = .txt mime = text/plain words = 7065 sentences = 359 flesch = 57 summary = Most structures of the SARS-CoV-2 S ectodomain currently available include two mutations, one to disrupt the furin cleavage site (RRAR to GSAS = S-GSAS), and a double proline mutation (PP) of residues 986-987, designed to prevent conformational change to the post-fusion state (Wrapp et al., 2020) . While the SARS-CoV-2 S ectodomain construct that includes mutations of residues K986 and V987, between the HR1 and CH subdomains (S2 domain), to prolines (PP) (named S-GSAS/PP in this study) (Figure 1 ) is widely used in the field, the origin of this PP construct was based upon the stabilization of the pre-fusion conformation of other coronavirus spikes (Pallesen et al., 2017; Walls et al., 2020; Wrapp et al., 2020) . Similar to observations made with the S-GSAS/D614G S ectodomain structure, the RBD up/down motion in the furin-cleaved G614 S ectodomain was associated with a movement in the SD1 domain and in the region of the RBD-to-NTD linker that joined the SD1 b sheet ( Figure 7C, S8B) . cache = ./cache/cord-346670-34wfy52f.txt txt = ./txt/cord-346670-34wfy52f.txt === reduce.pl bib === id = cord-347714-vxxhglx7 author = Abitogun, Folagbade title = COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date = 2020-10-14 pages = extension = .txt mime = text/plain words = 3707 sentences = 191 flesch = 44 summary = (10, 11) The structure of the spike glycoprotein of the virus is also an extended similarity with SARS-CoV, (4) which together with COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding other proteins of the virus are candidates for vaccine development and are being explored in different settings due to the active roles of the proteins in the infectivity of the virus. (18) However studies have shown that full length spike protein vaccines for SARS-CoV may lead to antibody mediated disease enhancement causing inflammatory and liver damage in animal models (19, 20) which is why in this manuscript, we applied immuno-informatics "in silico" approaches to identify potential CD8+ cytotoxic T Cell epitopes from proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. Multi-epitope Based Peptide Vaccine Design Using Three Structural Proteins (S, E, and M) of SARS-CoV-2: An In Silico Approach cache = ./cache/cord-347714-vxxhglx7.txt txt = ./txt/cord-347714-vxxhglx7.txt === reduce.pl bib === id = cord-347804-kxhasabe author = Luo, Ruibang title = Tracking cytosine depletion in SARS-CoV-2 date = 2020-10-26 pages = extension = .txt mime = text/plain words = 1084 sentences = 69 flesch = 63 summary = Results We built a website to track the composition change of mono-, di-, and tri-nucleotide of SARS-CoV-2 over time. Using 137,315 SARS-CoV-2 strains collected in ten months, we observed cytosine depletion at a rate of about one cytosine loss per month from the whole genome. We built an interactive website at http://www.bio8.cs.hku.hk/sarscov2 to show the mono-, di-, and tri-nucleotide composition trends of the whole genome and single genes. In Table 1 , we first compared the composition of nucleotides in multiple coronaviruses, including SARS-CoV-2 (an average of 76 strands collected from Dec 20, 2019 to Feb 15, 2020), SARS, MERS, and four that causes a common cold. Compared to SARS-CoV-2, which we assumed a relative mortality level of 3, the percentage of cytosine is lower in almost all of the eleven genes in the four common cold coronaviruses with a lower mortality level 1. The results are available on an interactive website at http://www.bio8.cs.hku.hk/sarscov2. cache = ./cache/cord-347804-kxhasabe.txt txt = ./txt/cord-347804-kxhasabe.txt === reduce.pl bib === id = cord-347982-omxcdiwt author = Basso, Fernanda Gisele title = Cooperative efforts on developing vaccines and therapies for COVID-19 Cooperative efforts for COVID-19 date = 2020-09-06 pages = extension = .txt mime = text/plain words = 3433 sentences = 168 flesch = 36 summary = The present research analyzes how the cooperation networks were set off considering the clinical trials on therapies and vaccines that were developed specifically to treat or prevent COVID-19. For the construction of cooperation networks, it was assumed that organizations signed agreements and/or treaties to develop specific studies, establishing joint ownership of the results and the new drug or vaccine, with the purpose of forming an alliance for innovation [20] . Regarding the distribution of the types of organizations that cooperate by category (Fig 3) , a greater diversity of partnerships was observed in antibodies, followed by vaccines and proteins, because these categories address complex therapies and require complementarity among several disciplines (e.g., adjuvants in Because clinical adoption and commercial success are due to the incorporation degree of existing practices in innovation processes [23] , the diffusion of disruptive technologies in this field may encounter greater challenges. cache = ./cache/cord-347982-omxcdiwt.txt txt = ./txt/cord-347982-omxcdiwt.txt === reduce.pl bib === id = cord-346532-4xpnd93d author = Strömich, Léonie title = Allosteric Hotspots in the Main Protease of SARS-CoV-2 date = 2020-11-06 pages = extension = .txt mime = text/plain words = 2370 sentences = 145 flesch = 60 summary = Here, we report the allosteric communication pathways in the main protease dimer by using two novel fully atomistic graph theoretical methods: Bond-to-bond propensity analysis, which has been previously successful in identifying allosteric sites without a priori knowledge in benchmark data sets, and, Markov transient analysis, which has previously aided in finding novel drug targets in catalytic protein families. Bond-to-bond propensities have been shown to successfully detect allosteric sites on proteins [43] and we here present 141 the results in the SARS-CoV-2 M pro to that effect. After a full Bond-to-bond propensity analysis and quantile regression to rank all residues, we are able to score the active 156 site to obtain a measure for the connectivity towards the catalytic center (Tab. S8). A complementary, node-based method, Markov Transient analysis (MTA) 276 identifies areas of the protein that are significantly connected to a site of interest, the source, such as the active site, and 277 obtains the signal propagation that connects the two sites at the atomistic level. cache = ./cache/cord-346532-4xpnd93d.txt txt = ./txt/cord-346532-4xpnd93d.txt === reduce.pl bib === id = cord-347472-n6811ens author = Rosebrock, Adam P. title = Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date = 2020-05-15 pages = extension = .txt mime = text/plain words = 6252 sentences = 344 flesch = 51 summary = The US Centers for Disease Control and Prevention (CDC) have specified and given emergency use authorization (EUA) for a SARS-CoV-2 molecular diagnostic used to detect viral RNA in clinical samples (2) . Genomic DNA is co-purified in quantities sufficient to generate strong positive signals for the CDC-specified extraction control during work-up of clinical RNA specimens. To test for the presence of control-affecting DNA, qPCR reactions lacking reverse transcriptase were performed on SARS-CoV-2-positive clinical samples using the CDC-specified RP primer and probe. All clinical samples tested generated unambiguous extraction control positive signals in the absence of reverse transcription, a reaction context that could not have detected virus an RNA virus ( Fig. 2A) Single-digit copies of genomic DNA are sufficient to generate a positive control signal using the CDC-designed assay. Due to the presence of co-purifying genomic DNA in clinical samples, loss of RNA integrity leads to false-negative results using the CDC-specified control. cache = ./cache/cord-347472-n6811ens.txt txt = ./txt/cord-347472-n6811ens.txt === reduce.pl bib === id = cord-348727-o38uplxe author = Beaudoin-Bussières, Guillaume title = Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals date = 2020-07-09 pages = extension = .txt mime = text/plain words = 920 sentences = 63 flesch = 54 summary = Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. Neutralizing activity against pseudoparticles bearing the SARS-CoV S 120 glycoprotein was detected in only 25% of convalescent plasma and exhibited low potency, as 121 previously reported (Figure 2) (14) . Of note, while we observed enhanced infectivity for the 122 D614G variant compared to its WT SARS-CoV-2 S counterpart ( Figure S3A ), no major 123 differences in neutralization with convalescent plasma were detected at both time-points ( Figure 124 S3B), thus suggesting that the D614G change does not affect the overall conformation of the 125 Spike, in agreement with recent findings (18) . 126 127 The capacity to neutralize SARS-CoV-2 S WT or D614G-pseudotyped particles 128 significantly correlated with the presence of RBD-specific IgG, IgM and anti-S antibodies 129 ( Figure S4 ). Interestingly, we observed a pronounced decrease (20-30%) in the percentage of 130 patients able to neutralize pseudoparticles bearing SARS-CoV-2 S glycoprotein between 6 and 131 10 weeks after symptoms onset. cache = ./cache/cord-348727-o38uplxe.txt txt = ./txt/cord-348727-o38uplxe.txt === reduce.pl bib === id = cord-346546-yffwd0dc author = Douangamath, Alice title = Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease date = 2020-05-27 pages = extension = .txt mime = text/plain words = 4059 sentences = 259 flesch = 56 summary = To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease. For 113 another series of hit compounds, containing a N-chloroacetyl piperidinyl-4-carboxamide 114 motif (Table S2 ) which displays lower reactivity and were not frequent hitters in previous 115 screens, we attempted crystallization despite their absence of labelling in the stringent 116 The bound fragments comprehensively sample all subsites of the active 287 site revealing diverse expansion vectors, and the electrophiles provide extensive, systematic 288 as well as serendipitous, data for designing covalent compounds. Crystal structure of SARS-CoV-2 main protease 763 provides a basis for design of improved alpha-ketoamide inhibitors cache = ./cache/cord-346546-yffwd0dc.txt txt = ./txt/cord-346546-yffwd0dc.txt === reduce.pl bib === id = cord-348635-1pb2ag9j author = Anand, Praveen title = SARS-CoV-2 selectively mimics a cleavable peptide of human ENaC in a strategic hijack of host proteolytic machinery date = 2020-04-30 pages = extension = .txt mime = text/plain words = 1658 sentences = 94 flesch = 51 summary = We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site (RRARSVAS), absent in any previous coronavirus sequenced, that results in mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). We extrapolate that the evolution of SARS-CoV-2 into a global coronavirus pandemic may be in part due to its targeted mimicry of human ENaC and hijack of the associated host proteolytic network. The overlap of the cell-types expressing ACE2 and ENaC-ɑ, and similar spatial distributions at the apical surfaces, suggest that SARS-CoV-2 may be leveraging the protease network responsible for ENaC cleavage. In order to extrapolate the tissue tropism of SARS-CoV-2 from the lens of the host proteolytic network, we assessed the co-expression of these proteases concomitant with the viral receptor ACE2 and ENaC-ɑ (Figure 2) . cache = ./cache/cord-348635-1pb2ag9j.txt txt = ./txt/cord-348635-1pb2ag9j.txt === reduce.pl bib === id = cord-348729-kejlm425 author = Liu, Xiaoyu title = Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection date = 2020-05-04 pages = extension = .txt mime = text/plain words = 3457 sentences = 178 flesch = 50 summary = SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. These determined infection mechanisms indicated that blocking the interaction of SARS-CoV-2-RBD and ACE2 would cause a direct neutralizing effect against virus. This information suggests that the ACE2 interface of SARS-CoV-2-RBD might have high immunogenicity, which would be a suitable targeting epitope to develop SARS-CoV-2-specific antibodies with potent neutralizing function by in vitro screening. We performed site-directed antibody screening by phage display and finally obtained one IgG antibody and three single domain antibodies with potent neutralizing activities for SARS-CoV-2. Notably, the eluted phage exhibited a stronger binding signal on SARS-CoV-2-RBD compared to that on SARS-CoV-2-RBD mut, especially those from the domain antibody library ( Figure 2C ), indicating an expected precleaning effect during selection. cache = ./cache/cord-348729-kejlm425.txt txt = ./txt/cord-348729-kejlm425.txt === reduce.pl bib === id = cord-349794-mhviub6e author = Le, Brian L. title = Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 date = 2020-10-23 pages = extension = .txt mime = text/plain words = 3810 sentences = 216 flesch = 43 summary = We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. By infecting human adenocarcinomic alveolar basal epithelial cells with SARS-CoV-2 and comparing to controls, the authors generated a list of 120 differentially expressed genes. Here, we applied our existing computational drug repositioning pipeline to identify drug profiles with significantly reversed differential gene expression compared to predicted inhibitors (including one tested in Calu-3) were incubated with SARS-CoV-2 infected human embryonic kidney 293T cells overexpressing ACE2 (293T-ACE2) with viral replication determined using an immunofluorescence-based assay. In this study, we applied our drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available RNA-seq data ( Figure 1 ). Here, we used a transcriptomics-based drug repositioning pipeline to predict therapeutic drug hits for three different input SARS-CoV-2 signatures, each of which came from distinct human cell or tissue origins. cache = ./cache/cord-349794-mhviub6e.txt txt = ./txt/cord-349794-mhviub6e.txt === reduce.pl bib === id = cord-346978-ubkqny8j author = Ranoa, Diana Rose E. title = Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction date = 2020-06-18 pages = extension = .txt mime = text/plain words = 6476 sentences = 325 flesch = 54 summary = 35 Using intact, γ-irradiated SARS-CoV-2 spiked into fresh human saliva, which was then heat treated at 95°C for 30 min, we observed outstanding virus detection when saliva samples were combined with either Tris-Borate-EDTA (TBE) or TE buffer ( Figure 3A) . Similar results were observed with heat-inactivated SARS-CoV-2, whereby the LOD was measured to be 5000 viral copies/mL for both RNA extraction of saliva samples and direct saliva-to-RT-qPCR, with greater detection if the virus was directly analyzed in water (Supporting Limit of Detection (LOD) for assessment of SARS-CoV-2 from saliva, comparing a process utilizing RNA isolation/purification to one that bypasses RNA isolation/purification. Altogether, these findings indicate that the optimized protocol (heat treatment of saliva samples at 95°C for 30 min / addition of TBE buffer and Tween 20) yields a LOD that is comparable to reported clinical viral shedding concentrations in oral fluid, thus emphasizing the translatability of the protocol to detecting SARS-CoV-2 in patient samples. cache = ./cache/cord-346978-ubkqny8j.txt txt = ./txt/cord-346978-ubkqny8j.txt === reduce.pl bib === id = cord-350627-4pgish5x author = Zhao, Yu title = Single-cell RNA expression profiling of ACE2,thereceptor of SARS-CoV-2 date = 2020-01-26 pages = extension = .txt mime = text/plain words = 1865 sentences = 129 flesch = 56 summary = Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. These studies showed that in normal human lung, ACE2 is mainly expressed by type II and type I alveolar epithelial cells. In total, we analyzed 43,134 cells derived from normal lung tissue of To further understand the special population of ACE2-expressing AT2, we performed gene ontology enrichment analysis to study which biological processes are involved with this cell population by comparing them with the AT2 cells not expressing ACE2. Of note, the 2 male donors have a higher ACE2-expressing cell ratio than all other 6 female author/funder. We also noticed that the only Asian donor (male) has a much higher ACE2Altogether, in the current study, we report the RNA expression profile of ACE2 in the human lung at single-cell resolution. https://doi.org/10.1101/2020.01.26.919985 doi: bioRxiv preprint author/funder. cache = ./cache/cord-350627-4pgish5x.txt txt = ./txt/cord-350627-4pgish5x.txt === reduce.pl bib === id = cord-350286-n7ylgqfu author = Giri, Rajanish title = When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date = 2020-04-03 pages = extension = .txt mime = text/plain words = 15827 sentences = 874 flesch = 56 summary = The results of this analysis are summarized in Table 2 , which clearly shows that most of the SARS-CoV-2 proteins contain at least one MoRF, indicating that disorder does play an important role in the functionality of these viral proteins. As it follows from Figure 3 , these cleavage sites are located within the IDPRs. In Human SARS CoV S protein, fusion peptide (residues 770-788) is located within a flexible region, is characterized by the mean disorder score of 0.232±0.053. Global analysis of intrinsic disorder in the replicase polyprotein 1ab Table 3 represents the PPID mean scores of 15 non-structural proteins (Nsps) derived from the Replicase polyprotein 1ab in SARS-CoV-2, Human SARS CoV, and Bat CoV. Similar to many other non-structural proteins of coronaviruses, Nsp15s from SARS-CoV-2, Human SARS, and Bat CoV are predicted to possess multiple flexible regions but contain virtually no IDPRs (see Figures 32A, 32B, and 32C) . cache = ./cache/cord-350286-n7ylgqfu.txt txt = ./txt/cord-350286-n7ylgqfu.txt === reduce.pl bib === id = cord-349364-vert186n author = Márquez-López, Cristina title = SARS-CoV-2 protein Nsp1 alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy-related PKP2 mutant date = 2020-09-14 pages = extension = .txt mime = text/plain words = 5246 sentences = 286 flesch = 48 summary = The fact that Nsp1 and PKP2 mutant R735X share similar phenotypes also suggests that direct SARS-CoV-2 heart infection could induce a transient ACM-like disease in COVID-19 patients, which may contribute to right ventricle dysfunction, observed in patients with poor survival prognosis. Using atomic force microscopy together with fluorescence imaging, we show that expression of PKP2 (c.2203C>T), encoding the R735X mutant found in ACM patients from different families (Alcalde et al., 2014; Gerull et al, 2004) alters cell mechanical stiffness, and alike Nsp1, modifies actomyosin cytoskeleton. All together, these results suggest that cytoplasmic localization of PKP2 either by a mutant involved in ACM development, or by Nsp1 hijack by SARS-CoV-2 infection can alter the integrity and assembly of the actin cytoskeleton by modulating the cortical distribution of Myh9 and Myh10. cache = ./cache/cord-349364-vert186n.txt txt = ./txt/cord-349364-vert186n.txt === reduce.pl bib === id = cord-348159-v5hrcl5k author = Sang, Eric R. title = Epigenetic Evolution of ACE2 and IL-6 Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates date = 2020-09-10 pages = extension = .txt mime = text/plain words = 2076 sentences = 117 flesch = 45 summary = Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. Third, we found that the evolutionary increase of 147 ACE2, and especially the IL-6 genes response to inflammatory and IFN signaling may 148 serve as epigenetic marker for COVID-19 susceptibility in some animal species including 149 humans. . This shows that ACE2 and especially IL-6 genes from CoV2(+) species contain CREs with significantly higher mPWM scores, indicating that in some vertebrate species, non-ISGs like ACE2 and especially IL-6 genes evolved to obtain high inductive propensity by inflammatory and IFN signaling, and may serve as epigenetic biomarkers (or triggers) for susceptibility prediction for COVID-19 and other ARD syndromes. cache = ./cache/cord-348159-v5hrcl5k.txt txt = ./txt/cord-348159-v5hrcl5k.txt === reduce.pl bib === id = cord-349684-2tioh80m author = Pezzotti, Giuseppe title = Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride date = 2020-06-20 pages = extension = .txt mime = text/plain words = 5388 sentences = 338 flesch = 51 summary = The present study compared the effects of exposing SARS-CoV-2 to aqueous suspensions of Si3N4 and aluminum nitride (AlN) particles and two controls, (i.e., a suspension of copper (Cu) particles (positive control) and a sham treatment (negative control)). In (c) and (d), results of RT-PCR tests for supernatants after 10 min exposure of virus suspension to Cu, AlN, and Si3N4 powders for viral N gene "set 1" and "set 2" primers are shown, respectively. The present work is the first to show that compounds capable of endogenous nitrogen-release, such as Si3N4 and AlN, can inactivate the SARS-CoV-2 virus at least as effectively as Cu. These results suggest that multiple antiviral mechanisms may be operative, such as RNA fragmentation, and in the case of Cu, direct metal ion toxicity; but while Cu and AlN supernatants demonstrated strong and partial cellular lysis, respectively, Si3N4 provoked no metabolic alterations. cache = ./cache/cord-349684-2tioh80m.txt txt = ./txt/cord-349684-2tioh80m.txt === reduce.pl bib === id = cord-349015-5oisrm5s author = Liu, Zhe title = Identification of a common deletion in the spike protein of SARS-CoV-2 date = 2020-04-02 pages = extension = .txt mime = text/plain words = 1182 sentences = 63 flesch = 57 summary = In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. By sequencing the whole genome of SARS-CoV-2, we identified two variants having deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. To investigate whether these deletions described above are random mutations occasionally identified in a strain or would commonly occur after cell passages, we performed whole genome sequencing on the other 21 SARS-CoV-2 viral strains collected after 2 rounds of cell passage in Vero-E6 or Vero cells (Supplemental Table) . cache = ./cache/cord-349015-5oisrm5s.txt txt = ./txt/cord-349015-5oisrm5s.txt === reduce.pl bib === id = cord-351321-6d2mn5ok author = Gouveia, Duarte title = Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window date = 2020-06-19 pages = extension = .txt mime = text/plain words = 6241 sentences = 294 flesch = 52 summary = Simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC-MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. By using a short LC gradient focusing on the region of interest identified in our previous study, we tested the detection of the virus in samples containing different quantities of viral peptides, as well as COVID-19 clinical samples, paving the way for the development of time-efficient viral diagnostic tests based on an alternative platform. To assess the performance of shotgun MS-based proteomics in detecting SARS-CoV-2 peptides in a background matrix consisting of nasopharyngeal swab protein material, we experimentally created tryptic peptidomes from i) a purified virus solution obtained from Vero E6 cells infected with a SARS-CoV-2 reference strain, and ii) nasopharyngeal swabs obtained from two healthy volunteers (Figure 1) . Simili swabs containing specific quantities of SARS-CoV-2 virus and the equivalent of 8.4% of the nasal matrix protein material collected during sampling were analysed by MS/MS with a short gradient. cache = ./cache/cord-351321-6d2mn5ok.txt txt = ./txt/cord-351321-6d2mn5ok.txt === reduce.pl bib === id = cord-351559-az4pgi9k author = Turjya, Rafeed Rahman title = Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date = 2020-06-29 pages = extension = .txt mime = text/plain words = 2438 sentences = 173 flesch = 48 summary = Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genes ADAR, EDN1, KYNU, MALL, TLR2 and YWHAG; and also AKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10 and PRKAR2A, host genes that interact with SARS-CoV-2 proteins. Conclusions Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option. cache = ./cache/cord-351559-az4pgi9k.txt txt = ./txt/cord-351559-az4pgi9k.txt === reduce.pl bib === id = cord-350935-p6euuop3 author = Doğan, Tunca title = CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date = 2020-09-15 pages = extension = .txt mime = text/plain words = 7066 sentences = 298 flesch = 45 summary = We aimed to address this issue by constructing a new biological and biomedical data resource, CROssBAR, a comprehensive system that integrates large-scale biomedical data from various resources and store them in a new NoSQL database, enrich these data with deep-learning-based prediction of relations between numerous biomedical entities, rigorously analyse the enriched data to obtain biologically meaningful modules and display them to users via easy-to-interpret, interactive and heterogenous knowledge graph (KG) representations within an open access, user-friendly and online web-service at https://crossbar.kansil.org. In this project, we aimed to address the current shortcomings by developing a comprehensive open access biomedical system entitled CROssBAR via integrating various biological databases to each other, inferring the missing relations between existing data points, and constructing informative knowledge graphs based on specific biomedical components/terms such as a disease/phenotype, biological process, gene/protein and drug/compound, or specific combinations of them. cache = ./cache/cord-350935-p6euuop3.txt txt = ./txt/cord-350935-p6euuop3.txt === reduce.pl bib === id = cord-353161-mtq6yh25 author = Rodrigues, João PGLM title = Insights on cross-species transmission of SARS-CoV-2 from structural modeling date = 2020-06-05 pages = extension = .txt mime = text/plain words = 6169 sentences = 369 flesch = 56 summary = We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Collectively, our results provide a structural framework that explains why certain animal species are not susceptible to SARS-CoV-2 infection, and also suggests potential mutations that can enhance binding to the viral RBD. Although it is well-known that docking scores do not quantitatively correlate with experimental binding affinities [19] , these scores suggest that SARS-CoV-2 neg species lack one or more key ACE2 residues that contribute significantly to the interaction with RBD. Models of SARS-CoV-2 neg species -chicken, duck, guinea pig, mouse, and rat -generally have higher (worse) HADDOCK scores than average (Figure 2 ), suggesting that these species' non-susceptibility to infection could stem from deficient RBD binding to ACE2. cache = ./cache/cord-353161-mtq6yh25.txt txt = ./txt/cord-353161-mtq6yh25.txt === reduce.pl bib === id = cord-350558-qfdp4ov9 author = Shaban, Mohammed Samer title = Inhibiting coronavirus replication in cultured cells by chemical ER stress date = 2020-08-26 pages = extension = .txt mime = text/plain words = 5077 sentences = 297 flesch = 58 summary = We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. A detailed proteomics analysis reveals multiple thapsigargin-78 regulated pathways and a network of proteins that are suppressed by CoV but (re)activated by 79 chemically stressed infected cells. we determined the expression levels of 166 components of the ER stress pathway KEGG 04141 85 "protein processing in endoplasmic reticulum" in human HuH7 liver cells, a commonly used cellular 86 model for CoV replication, in response to infections with HCoV-229E and MERS-CoV, respectively. The highly inducible HERPUD1 protein has an essential scaffolding function for the organization of searching our proteomics data for further ERAD factors we were able to retrieve a total of 34 (for 284 MERS-CoV) and 20 (for SARS-CoV-2) proteins of the canonical ERQC and ERAD pathways for 285 which a differential expression was observed in virus-infected cells treated with thapsigargin (Fig. 286 5H) . cache = ./cache/cord-350558-qfdp4ov9.txt txt = ./txt/cord-350558-qfdp4ov9.txt === reduce.pl bib === id = cord-351472-ch004jxy author = Vashi, Yoya title = Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens date = 2020-04-10 pages = extension = .txt mime = text/plain words = 1335 sentences = 161 flesch = 71 summary = The present study followed computational approaches to identify Band T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics. We identified 18 linear epitopes, predicted by ElliPro (IEDB), which contains regions from 128 19 of our selected peptides highlighted in red in Table 2 . Using the same module, B-cell discontinuous epitopes were predicted, which gave 16 133 epitope regions that contained regions from 18 of our selected peptides highlighted in red 134 (Table 3) . Regions from all of our selected peptides were found to be potential T-cell 7 epitope(s) with high binding affinity with HLA-A and HLA-B alleles, except one. IEDB ElliPro predicted discontinuous epitopes for spike protein of SARS-CoV-2. cache = ./cache/cord-351472-ch004jxy.txt txt = ./txt/cord-351472-ch004jxy.txt === reduce.pl bib === id = cord-350821-0qfoc553 author = Jahromi, Reza title = Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 date = 2020-06-01 pages = extension = .txt mime = text/plain words = 1941 sentences = 113 flesch = 46 summary = title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Twelve sanitizing fluids with different recipes, as shown in Table 1 , were prepared to examine the effect of individual components and mixtures on evaporation rate and SARS-CoV-2 virucidal efficiency of the solutions. Furthermore, the addition of 3% dish soap to the ethanol solution (S1) increased the evaporation time by about 63% from 24 to 39 s (of fluid S9), as shown in Figure 2 . cache = ./cache/cord-350821-0qfoc553.txt txt = ./txt/cord-350821-0qfoc553.txt === reduce.pl bib === id = cord-353554-98uzivsk author = Zhang, Zheng title = Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors date = 2018-03-08 pages = extension = .txt mime = text/plain words = 2190 sentences = 122 flesch = 56 summary = title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. 64 The virus-receptor interaction was reported to be a principal determinant of viral host 65 range, tissue tropism and cross-species infection [11, 16, 22] . However, we found the viral receptor tended not to interact with each 248 other ( Figure S3D 270 Since the virus has to compete with other proteins for binding to the receptor, proteins (Table S5) . cache = ./cache/cord-353554-98uzivsk.txt txt = ./txt/cord-353554-98uzivsk.txt === reduce.pl bib === id = cord-352073-rdhjj72g author = Taniwaki, S.A title = Resource optimization in COVID-19 diagnosis date = 2020-06-26 pages = extension = .txt mime = text/plain words = 1910 sentences = 98 flesch = 57 summary = The emergence and rapid dissemination worldwide of a novel Coronavirus (SARS-CoV-2) results in decrease of swabs availability for clinical samples collection, as well as, reagents for RT-qPCR diagnostic kits considered a confirmatory test for COVID-19 infection. This manuscript reports on the optimization of the Charité and the CDC RT-qPCR protocols for SARS-CoV-2 detection regarding concentration and volumes of reagents for both probe and intercalant agent-based platforms, as well as on the substitution of rayon swabs for cotton swabs for sample collection. Performance of E and RdRp genes of SARS-CoV-2 RT-qPCRs, based on final reaction volume of 10 µL with 2 µL of RNA (Table 1) , were verified with a relative standard curve built with 10 -2 to 10 -8 dilutions of positive RNA control. Tabela 4 -Probe-based RT-qPCR to the E gene of serial dilutions of SARS-CoV-2 sampled with cotton and rayon swabs. cache = ./cache/cord-352073-rdhjj72g.txt txt = ./txt/cord-352073-rdhjj72g.txt === reduce.pl bib === id = cord-350817-tmszrtju author = Hoepel, Willianne title = Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses date = 2020-07-13 pages = extension = .txt mime = text/plain words = 5626 sentences = 296 flesch = 47 summary = Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. Taken together, these data demonstrate that anti-Spike IgG immune complexes generated from serum of severely ill COVID-19 patients induce a strong pro-inflammatory response by (otherwise immunosuppressive) human M2 macrophages, which is characterized by high production of classical cytokine storm mediators such as IL-1β, IL-6, IL-8, and TNF. As shown in Figure 4A , the used human macrophage model highly expressed all FcγRs. To determine whether FcγRs are involved in activation by anti-Spike immune complexes, we blocked the different FcγRs with specific antibodies during stimulation, and analyzed cytokine production. In conclusion, our data show that anti-Spike IgG from serum of severely ill COVID-19 patients strongly amplifies pro-inflammatory responses by human macrophages, and can contribute to subsequent endothelial barrier disruption and thrombosis. cache = ./cache/cord-350817-tmszrtju.txt txt = ./txt/cord-350817-tmszrtju.txt === reduce.pl bib === id = cord-353911-hp6s6ebh author = Petráš, Marek title = Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein date = 2020-11-03 pages = extension = .txt mime = text/plain words = 2119 sentences = 134 flesch = 54 summary = title: Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein Our aim was to design a semi-split inactivated vaccine offering a wide range of multi-epitope determinants important for the immune system including not only the spike (S) protein but also the envelope, membrane and nucleocapsid proteins. The above laboratory procedure generated a semi-split inactivated vaccine, i.e., a vaccine with 307 the S protein separated from the viral particle exhibiting an early, both humoral and cellular, 308 immune response. Safety and immunogenicity of the ChAdOx1 nCoV-386 19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, 387 randomised controlled trial An in-depth investigation of the safety and immunogenicity of an 468 inactivated SARS-CoV-2 vaccine A double-inactivated 499 whole virus candidate SARS coronavirus vaccine stimulates neutralising and 500 protective antibody responses. Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity 526 cache = ./cache/cord-353911-hp6s6ebh.txt txt = ./txt/cord-353911-hp6s6ebh.txt === reduce.pl bib === id = cord-353129-ivbf4kuq author = Faryami, Ahmad title = Open source 3D printed Ventilation Device date = 2020-05-22 pages = extension = .txt mime = text/plain words = 2331 sentences = 118 flesch = 50 summary = The following is intended to review the development and testing of a 3D printed and open-source mechanical ventilation device that is capable of adjusting breathing rate, volume, and pressure simultaneously and was designed according to the latest clinical observations of the current pandemic. This open-source positive pressure ventilation device (OSPPVD) is a response to the shortages in the hospitals' ventilation capacity, which has been reported to be essential to many COVID-19 patients throughout the world. According to the initial reports published by healthcare providers, the loss of compliance due to the onset of fibrosis in the lungs is observed in patients diagnosed with severe cases of COVID-19 infection 9 . An advantage of OSPPVD presented here is its capability to perform hyperventilation with high flow rates under relatively wide pressure range from 5 2 that would allow the delivery of oxygen without the over-expansion of the lungs while being able to supply pressurized air as high as 40 or 50 2 even though the current setup is designed to only reach 30 2 . cache = ./cache/cord-353129-ivbf4kuq.txt txt = ./txt/cord-353129-ivbf4kuq.txt === reduce.pl bib === id = cord-352943-ztonp62x author = Nagpal, Sunil title = What if we perceive SARS-CoV-2 genomes as documents? Topic modelling using Latent Dirichlet Allocation to identify mutation signatures and classify SARS-CoV-2 genomes date = 2020-08-20 pages = extension = .txt mime = text/plain words = 2776 sentences = 174 flesch = 47 summary = Here we describe how SARS-CoV-2 genomic mutation profiles can be structured into a 'Bag of Words' to enable identification of signatures (topics) and their probabilistic distribution across various genomes using LDA. Use of the non-phylogenetic albeit classical approaches like topic modeling and other data centric pattern mining algorithms is therefore proposed for supplementing the efforts towards understanding the genomic diversity of the evolving SARS-CoV-2 genomes (and other pathogens/microbes). In fact, Latent Dirichlet Allocation (LDA), an unsupervised machine learning approach, is particularly known for identifying latent topics in large document collections and deciphering the words that define the inferred topics using a generative statistical model. Classical LDA was employed to generate topic models leading to identification of 16 amino acid mutation signatures and 18 nucleotide mutation signatures (equivalent to topics) in the corpus of chosen genomes through rigorous hyper-parameter tuning for coherence optimization (Figure 2) . cache = ./cache/cord-352943-ztonp62x.txt txt = ./txt/cord-352943-ztonp62x.txt === reduce.pl bib === id = cord-353099-38bz0acw author = Tang, Mei San title = Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays date = 2020-07-02 pages = extension = .txt mime = text/plain words = 1034 sentences = 70 flesch = 51 summary = Methods 67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Results The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. Conclusion COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. The correlation of the SARS-CoV-2 neutralizing titer with the ratio reported by the 162 Roche, Abbott, and EI assays was 0.29, 0.47, and 0.46 respectively (Figure 2A-C) . Increased neutralizing antibody titers were also higher in patients that were intubated, 201 had cardiac injury, or AKI relative to those with milder COVID-19 symptoms ( Figure 202 4B-D). cache = ./cache/cord-353099-38bz0acw.txt txt = ./txt/cord-353099-38bz0acw.txt === reduce.pl bib === id = cord-353742-k4gxww2c author = Arévalo, AP title = Ivermectin reduces coronavirus infection in vivo: a mouse experimental model date = 2020-11-02 pages = extension = .txt mime = text/plain words = 721 sentences = 66 flesch = 48 summary = SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases. cache = ./cache/cord-353742-k4gxww2c.txt txt = ./txt/cord-353742-k4gxww2c.txt === reduce.pl bib === id = cord-353209-qkhfp66l author = Steiner, Daniel J. title = Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date = 2020-06-16 pages = extension = .txt mime = text/plain words = 2517 sentences = 129 flesch = 45 summary = We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. Aminereactive substrates for fabrication of AIR arrays were provided by Adarza BioSystems, Inc. For ELISA assays, SARS-CoV-2 full-length spike and RBD were produced in-house using a mammalian expression system, 20,21 as was influenza A/H1N1/California 2009 hemagglutinin. To that end, we have presented preliminary data on a 15-plex array on the AIR platform, developed in response to the need to study SARS-CoV-2 but incorporating antigens for other coronaviruses and influenza. Responses to SARS-CoV-2 antigens on the array effectively discriminated between serum samples from uninfected and COVID-19 convalescent subjects, with generally good correlation to ELISA data. cache = ./cache/cord-353209-qkhfp66l.txt txt = ./txt/cord-353209-qkhfp66l.txt === reduce.pl bib === id = cord-353877-wzndpcq3 author = Albagi, Sahar Obi Abd title = A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach date = 2020-05-20 pages = extension = .txt mime = text/plain words = 3747 sentences = 264 flesch = 58 summary = Due to the current COVID-19 pandemic, the rapid discovery of a safe and effective vaccine is an essential issue, consequently, this study aims to predict potential COVID-19 peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. Consistent with global efforts, this study aims to predict potential COVID-19 Peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. The molecular docking results showed that the Spike peptide FTISVTTEI has the lowest docking energy score with the MHC I HLA-B1503 allele, hence it is predicted to have the highest binding affinity. Regarding the interaction with the MHC II molecule, the Spike peptide EVFNATRFASVYAWN showed the lowest docking energy score with the three MHC II alleles HLA-DPA1*01:03/DPB1*02:01, HLA-DQA1*01:02/DQB1*06:02, and HLA-DRB1, hence it is predicted to have the highest binding affinity to the three alleles. cache = ./cache/cord-353877-wzndpcq3.txt txt = ./txt/cord-353877-wzndpcq3.txt === reduce.pl bib === id = cord-355728-wivk0bm0 author = Schoof, Michael title = An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation date = 2020-08-17 pages = extension = .txt mime = text/plain words = 3613 sentences = 377 flesch = 68 summary = Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Class I nanobodies emerged with highly 144 variable activity in this assay with Nb6 and Nb11 as two of the most potent clones with IC50 145 values of 370 and 540 nM, respectively (Table 1) To define the binding sites of Nb6 and Nb11, we determined their cryogenic electron 156 microscopy (cryo-EM) structures bound to Spike* ( Fig. 2A state RBDs only contacts a single RBD (Fig. 2D) . 277 278 mNb6-tri displays further gains in potency in both pseudovirus and live SARS-CoV-2 infection 279 assays with IC50 values of 120 pM (5.0 ng/mL) and 54 pM (2.3 ng/mL), respectively (Fig. 4H-I, 280 Table 1). cache = ./cache/cord-355728-wivk0bm0.txt txt = ./txt/cord-355728-wivk0bm0.txt === reduce.pl bib === id = cord-355811-aq7p1uxo author = Węglarz-Tomczak, Ewelina title = Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds date = 2020-05-21 pages = extension = .txt mime = text/plain words = 2008 sentences = 151 flesch = 57 summary = A collection of twelve organoselenium compounds, structural analogues of antioxidant drug ebselen were screened for inhibition of the papain-like protease (PLpro) from the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, CoV2). In recent studies, peptide analogues [11] and ebselen [12] have been identified as highly active inhibitors for PL pro . We show that some of them indeed possess higher activity than ebselen, that has been recently reported as PL pro CoV2 inhibitor [12] , and, thus, could be considered as novel potential drugs against COVID-19. In this work, we used the ebselen derivatives/analogues library and performed a comprehensive inhibition study of PL pro CoV2. In the case of PL pro SARS, none of the presented ebselen derivatives was able to block the enzyme. Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design Ebselen as a highly active inhibitor of PL pro CoV2 cache = ./cache/cord-355811-aq7p1uxo.txt txt = ./txt/cord-355811-aq7p1uxo.txt === reduce.pl bib === id = cord-356005-zhwtlik6 author = Yazhini, Arangasamy title = D614G substitution enhances the stability of trimeric SARS-CoV-2 spike protein date = 2020-11-02 pages = extension = .txt mime = text/plain words = 2626 sentences = 142 flesch = 47 summary = Here, using in-silico mutagenesis and energy calculations, we analyzed inter-residue interaction energies and thermodynamic stability of the dominant (G614) and the ancestral (D614) variants of spike protein trimer in 'closed' and 'partially open' conformations. Such changes in the local interaction energies enhance the thermodynamic stability of the spike protein trimer as free energy difference (ΔΔG) upon glycine substitution is −2.6 kcal/mol for closed conformation and −2.0 kcal/mol for open conformation. Our results on the structural and energetic basis of enhanced stability hint that G614 may confer increased availability of functional form of spike protein trimer and consequent in higher infectivity than the D614 variant. To study the effect of D614G variation on the thermodynamic stability of the spike protein trimer, we calculated free energy changes upon aspartate to glycine substitution using buildmodel function in FoldX (Schymkowitz et al., 2005) . The table contains details of frustration index of inter-residue contacts present at 614th position of spike protein trimer in closed and partially open conformations. cache = ./cache/cord-356005-zhwtlik6.txt txt = ./txt/cord-356005-zhwtlik6.txt === reduce.pl bib === id = cord-354725-lqio7l8k author = Arumugam, Arunkumar title = A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings date = 2020-04-30 pages = extension = .txt mime = text/plain words = 3478 sentences = 203 flesch = 64 summary = Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. 5 Despite its established performance in sensitivity and specificity, RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many resource limiting settings. Two water baths (one for denaturation and one for the reverse transcription and then the annealing/extension steps) were made using food storage plastic containers heated by sous vide immersion heaters. We tested this rapid water bath RT-PCR approach using untreated or heat-inactivated samples directly added to one-step RT-PCR master mixes without an RNA extraction step. Extracted templates from COVID-19 positive clinical specimens and contrived negative samples were tested using water bath-based RT-PCR. With a 3-minute RNA extraction protocol, we were able to get positive RT-PCR results with all ten COVID-19 positive clinical samples. cache = ./cache/cord-354725-lqio7l8k.txt txt = ./txt/cord-354725-lqio7l8k.txt === reduce.pl bib === id = cord-355758-tk7eturq author = Berrio, Alejandro title = Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function date = 2020-09-22 pages = extension = .txt mime = text/plain words = 2175 sentences = 156 flesch = 49 summary = Background The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease (COVID-19) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein based on the ratio of synonymous to nonsynonymous substitution. In addition, we find other likely targets of positive selection within the genome of SARS-CoV-2, specifically within the genes encoding Nsp4 and Nsp16. In Importantly, we also detected signals of positive selection in two additional regions of the 414 SARS-CoV-2 genome, specifically within the genes encoding Nsp4 and Nsp16 (Fig 1A) . Comparative analysis of coronavirus genomic RNA structure reveals 718 conservation in SARS-like coronaviruses. cache = ./cache/cord-355758-tk7eturq.txt txt = ./txt/cord-355758-tk7eturq.txt === reduce.pl bib === id = cord-356090-oj3d9ail author = Gorgun, D. title = Binding Mode of SARS-CoV2 Fusion Peptide to Human Cellular Membrane date = 2020-10-27 pages = extension = .txt mime = text/plain words = 6065 sentences = 277 flesch = 51 summary = Here, we use an array of molecular dynamics (MD) simulations taking advantage of the Highly Mobile Membrane Mimetic (HMMM) model, to investigate the interaction of the SARS-CoV2 FP with a lipid bilayer representing mammalian cellular membranes at an atomic level, and to characterize the membrane-bound form of the peptide. Taken into account the sequence conservation among the viral FPs and the results of mutagenesis studies establishing the role of specific residues in the helical portion of the FP in membrane association, we propose that the helix-binding mode represents more closely the biologically relevant form. In this study, using molecular dynamics simulations, we describe how the fusion peptide from the SARS-CoV2 virus binds human cellular membranes and characterize, at an atomic level, lipid-protein interactions important for the stability of the bound state. In this study, using a large set of simulations, we describe how the SARS-CoV2 FP binds mammalian cellular membranes and characterize, at atomic details, lipid-protein interactions important for the stability of the bound state. cache = ./cache/cord-356090-oj3d9ail.txt txt = ./txt/cord-356090-oj3d9ail.txt === reduce.pl bib === id = cord-351011-v4zmksio author = Golden, Joseph W. title = Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date = 2020-07-09 pages = extension = .txt mime = text/plain words = 4650 sentences = 268 flesch = 52 summary = In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. In comparison with the normal lung architecture in uninfected control animals, infected mice necropsied on day 3, and those succumbing to disease on days 5-11, had varying levels of lung injury including area of lung consolidation characterized by inflammation/expansion of 145 alveolar septa with fibrin, edema and mononuclear leukocytes and infiltration of vessel walls by numerous mononuclear leukocytes (Fig 3A, Fig S4, and Table S1 ). Importantly, in our study some animals at the lower dose survived infection despite significant Infection of K18-hACE2 mice by SARS-CoV-2 produces a disease similar to that observed in acute human cases, with development of an acute lung injury associated with edema, production 285 of inflammatory cytokines and the accumulation of mononuclear cells in the lung. cache = ./cache/cord-351011-v4zmksio.txt txt = ./txt/cord-351011-v4zmksio.txt === reduce.pl bib === id = cord-354868-pqn59ojj author = Yao, Hebang title = A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2 date = 2020-09-25 pages = extension = .txt mime = text/plain words = 3231 sentences = 236 flesch = 58 summary = title: A high-affinity RBD-targeting nanobody improves fusion partner's potency against SARS-CoV-2 Considerable research have been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. A high-affinity RBD binder without neutralizing activity 85 Previously, we generated 99 sybodies from three highly diverse synthetic libraries by ribosome and phage display with in vitro selections against the SARS-CoV-2 RBD. Consistent with its inability to neutralize SARS-CoV-2 pseudovirus, SR31 did not affect RBD-ACE2 binding (Fig. 1C) . Most RBD-targeting neutralizing antibodies, including neutralizing nanobodies characterized so far (8, 13-15, 19, 20, 22-24, 26-28, 34, 35, 37) , engage the RBD at the receptor-binding motif (RBM) (Fig. 3A) , thus competing off ACE2 and preventing viral entry. Taken together, the structural data rationalize the high-affinity binding between SR31 and RBD, and its inability to neutralize SARS-CoV-2. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 cache = ./cache/cord-354868-pqn59ojj.txt txt = ./txt/cord-354868-pqn59ojj.txt === reduce.pl bib === id = cord-353777-t8q99tlq author = Jia, Yong title = Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date = 2020-04-11 pages = extension = .txt mime = text/plain words = 3217 sentences = 180 flesch = 58 summary = The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. The discrepant phylogenies for the spike protein and its 23 receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARSDespite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that 25 leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27 th January 2020 from 26 cache = ./cache/cord-353777-t8q99tlq.txt txt = ./txt/cord-353777-t8q99tlq.txt === reduce.pl bib === id = cord-353731-7xn7m662 author = Heaton, Brook E. title = SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2 date = 2020-08-18 pages = extension = .txt mime = text/plain words = 2233 sentences = 139 flesch = 51 summary = sgRNA sequencing data indicated that the host gene with the highest probability of being 125 required for SARS-CoV-2 infection was the serine/arginine-rich protein kinase, SRPK1 126 ( Figure 1B) . We next wanted to define the degree to which inhibition of SRPK1 mediated N 141 phosphorylation would affect viral replication, especially since other non-SRPK1 kinases 142 have been predicted to be responsible for SARS-CoV-2 protein phosphorylation 12,13 . SRPIN340 treatment of cells infected with the 183 alphacoronavirus 229E (which is only distantly related to betacoronavirus SARS-CoV-2) 184 inhibited the virus by more than 1,000-fold at non-toxic concentrations of the drug ( Figure 185 2G-H). Human papillomavirus type 1 E1^E4 protein is a potent 533 inhibitor of the serine-arginine (SR) protein kinase SRPK1 and inhibits 534 phosphorylation of host SR proteins and of the viral transcription and replication 535 regulator E2 cache = ./cache/cord-353731-7xn7m662.txt txt = ./txt/cord-353731-7xn7m662.txt === reduce.pl bib === id = cord-354315-yfn9vaan author = Meirson, Tomer title = Structural basis of SARS-CoV-2 spike protein induced by ACE2 date = 2020-05-24 pages = extension = .txt mime = text/plain words = 5190 sentences = 253 flesch = 49 summary = This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The critical step in SARS-CoV-2 infection which involves the transition between a metastable prefusion state to a stable post-fusion state is triggered by binding to ACE2 which induces conformational changes in the RBD and the hinge region (Gui, et al., 2017; Pallesen, et al., 2017; Song, et al., 2018; Walls, et al., 2020) . To gain insights into the effects of ACE2 interaction on the S protein of SARS-COV-2, we analyzed the intramolecular structural variations in the bound versus the unbound-closed Numerous structures of the prefusion human CoV S proteins were determined at different states, and the key regions responsible for the interaction with the receptor were previously reported (Lan, et al., 2020; Shang, et al., 2020; Walls, et al., 2020; Wan, et al., 2020; Wrapp, et al., 2020; Yan, et al., 2020) . cache = ./cache/cord-354315-yfn9vaan.txt txt = ./txt/cord-354315-yfn9vaan.txt === reduce.pl bib === id = cord-356264-q0yqnlyl author = Armijos-Jaramillo, Vinicio title = SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability date = 2020-03-23 pages = extension = .txt mime = text/plain words = 4974 sentences = 253 flesch = 53 summary = With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor hACE2. We employ a multidisciplinary approach to look for evidence of diversifying selection on the S-protein gene, and model the interactions between human ACE2 (hACE2) and the RBD of selected coronavirus strains, which ultimately afforded us novel insights detailing virus and host cell interactions. All these experiments were performed again using the S-protein genes of a shorter list of accessions and more distantly related (broad dataset) to SARS-COV-2 (AY304488, AY395003, DQ412043, FJ882957, KY417144, MG772933, MG772934, MN908947, NC_004718) to test the reproducibility of the predicted branches and sites under positive selection. Modeling results suggest that interference with the hot spot 353 could be and effective strategy for inhibiting the recognition of the RBD of the SARS-COV-2 spike protein by its human host receptor ACE2 and hence prevent infections. cache = ./cache/cord-356264-q0yqnlyl.txt txt = ./txt/cord-356264-q0yqnlyl.txt === reduce.pl bib === id = cord-355397-y69bk5jc author = Caruso, Ícaro P. title = Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism date = 2020-09-06 pages = extension = .txt mime = text/plain words = 5105 sentences = 297 flesch = 55 summary = Here, we used molecular dynamics (MD) simulations to study the binding of SARS-CoV-2 N-NTD to non-specific (NS) and TRS dsRNAs. We probed dsRNAs' Watson and Crick (WC) base-pairing over 25 replicas of 100 ns MD simulations, showing that only one N-NTD of dimeric N is enough to destabilize dsRNAs, initiating melting. We calculated the structural model of the N-NTD:dsTRS complex based on the experimental data for the N-NTD interaction with a non-specific dsRNA (5'-CACUGAC-3') (dsNS) (16) using the HADDOCK 2.2 server (20) . In contrast to the decrease in the number of intramolecular hydrogen bonds between the sense and anti-sense strands of dsRNAs (WC base-pairing) due to N-NTD binding, we observed an increase in the average number of intermolecular hydrogen bonds formed between the nitrogenous bases of dsTRS and N-NTD (protein-RNA interaction) along the 100 ns MD simulation, whereas for dsNS, this average value was constant ( Figure 3B top). cache = ./cache/cord-355397-y69bk5jc.txt txt = ./txt/cord-355397-y69bk5jc.txt ===== Reducing email addresses cord-102376-wk70iipl cord-102588-vpu5w9wh cord-102356-knvfbuzv cord-102502-hroxg2u1 cord-102823-zult69f2 cord-102511-7zgd45fl cord-102749-tgka0pl0 cord-102916-t2lcd300 cord-103081-k7ev5qkn cord-103105-iqjksoim cord-103015-3dxwbmd2 cord-103108-vmze2mdx cord-103204-gt6upfri cord-103377-j1mmx7k7 cord-103688-n7hzpbyf cord-103876-2rg2qtdq cord-103915-rzy7mejb cord-103895-dt0ers70 cord-104001-5clslvqb cord-267482-afqfymbq cord-264051-ps0x2es1 cord-271978-j5enftje cord-277487-jgbjxgh1 cord-280025-4hmecfi0 cord-286001-pu1fetq7 cord-285592-0in22wzv cord-293826-2p7dqacd cord-302733-rfuyd041 cord-311114-ggcpsjk8 cord-312305-ll29frwc cord-321166-nvphu1fm cord-329102-2y49kcwu cord-346670-34wfy52f cord-347804-kxhasabe Creating transaction Updating adr table ===== Reducing keywords cord-102219-d3gkfo7s cord-102145-bi8jyz6r cord-102156-v98vrely cord-102184-8u73adnk cord-102206-mb0qcd0b cord-102189-wo9gg7nx cord-102279-ena1usqv cord-102376-wk70iipl cord-102350-e1vc2q4j cord-102158-5xg40s4o cord-102178-ju826pao cord-102231-cquxqbc2 cord-102364-t5bt2eb4 cord-102151-26lumewy cord-102336-ex3zlq38 cord-102463-d440jsek cord-102530-wetqqt2i cord-102270-rfhtlodc cord-102383-m5ahicqb cord-102504-d840uu3e cord-102226-aioqogaw cord-102321-csdezu6y cord-102199-mc6zruyx cord-102257-da4zn49x cord-102406-9gnbe3n1 cord-102324-tu804znm cord-102370-5uy8dq18 cord-102486-llmfgavd cord-102451-pcuzylva cord-102449-6foh1uvn cord-102412-cnlvyey4 cord-102358-kf04tra6 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cord-355728-wivk0bm0 cord-355811-aq7p1uxo cord-356005-zhwtlik6 cord-355758-tk7eturq cord-354725-lqio7l8k cord-350286-n7ylgqfu cord-353777-t8q99tlq cord-353731-7xn7m662 cord-354868-pqn59ojj cord-351011-v4zmksio cord-354315-yfn9vaan cord-356090-oj3d9ail cord-356264-q0yqnlyl cord-355397-y69bk5jc Creating transaction Updating pos table Building ./etc/reader.txt cord-262119-s6hc7fxs cord-333703-1ku3jc9s cord-262470-nkql7h9x cord-350286-n7ylgqfu cord-308428-zw26usmh cord-335075-6wo2o5pp number of items: 701 sum of words: 2,524,922 average size in words: 3,970 average readability score: 52 nouns: cells; protein; cell; virus; data; analysis; infection; expression; proteins; coronavirus; sequence; sequences; structure; samples; study; model; receptor; results; time; spike; genes; patients; gene; genome; number; disease; host; response; mice; mutations; antibody; studies; activity; antibodies; type; viruses; control; system; residues; site; lung; domain; acid; levels; replication; treatment; binding; mutation; detection; drug verbs: using; shown; bound; based; identify; including; found; performed; compare; suggested; observe; followed; indicate; provide; increasing; containing; associated; revealed; induces; reported; expressed; predict; detect; determine; generated; describe; saw; tested; infected; obtained; reduced; cause; resulting; given; known; represents; developing; targeting; allowing; demonstrate; related; making; required; mediated; lead; analyzed; considered; neutralize; treated; added adjectives: viral; human; high; different; specific; immune; single; respiratory; severe; non; positive; similar; clinical; low; new; higher; first; molecular; structural; multiple; acute; novel; potential; significant; large; available; antiviral; anti; several; many; covid-19; small; key; possible; negative; functional; important; lower; present; cellular; like; dependent; inflammatory; full; genomic; total; previous; global; infected; consistent adverbs: also; however; well; respectively; highly; therefore; previously; significantly; even; first; together; directly; finally; recently; furthermore; still; next; less; interestingly; specifically; relatively; moreover; currently; prior; additionally; potentially; especially; much; likely; often; rather; indeed; rapidly; notably; least; particularly; approximately; strongly; similarly; already; fully; hence; now; importantly; closely; differentially; instead; clearly; subsequently; widely pronouns: we; it; our; their; its; they; i; them; us; his; itself; one; themselves; he; you; your; my; her; she; me; imagej; em; ourselves; hao; si3n4; s; igg1; cbae-1; u; rrbd-15; ours; nlrp12; mine; iosns; il-1β; directms1; ıt; y-27632; usa_wa1/2020; rad5; nsp7; mrnas; l452; l270; ippa17-a04; igfbp2; https://github.com/ababaian/serratus; hace2; fncas9; etn proper nouns: SARS; CoV-2; Fig; RNA; ACE2; COVID-19; T; S; RBD; CoV; C; Table; S1; Figure; PCR; Coronavirus; S2; Supplementary; N; MERS; M; China; RT; G; TMPRSS2; Human; Spike; DOI; Vero; sha; A; B; Protein; IFN; Data; Wuhan; PBS; CD8; F; K; II; Virus; ±; HLA; pH; CD4; L; D; USA; Disease keywords: sars; rna; ace2; cov-2; cell; rbd; covid-19; protein; dna; pcr; supplementary; spike; sequence; virus; tmprss2; hla; gene; structure; mutation; mers; ifn; drug; data; antibody; vero; disease; cd8; mouse; d614; cd4; bat; variant; vaccine; tms; site; sample; human; elisa; eeg; crispr; coronavirus; zikv; usa; time; table; sequencing; selection; receptor; read; pro one topic; one dimension: sars file(s): https://doi.org/10.1101/823781 titles(s): Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex three topics; one dimension: sars; sars; cells file(s): https://doi.org/10.1101/2019.12.26.888511, https://doi.org/10.1101/2020.04.15.037564, https://doi.org/10.1101/2020.10.05.326850 titles(s): Neurophysiological Correlates of the Dunning-Kruger Effect | Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment | Taxonomic revision of the threatened African genus Pseudohydrosme Engl. (Araceae), with P. ebo, a new, Critically Endangered species from Ebo, Cameroon five topics; three dimensions: sars cov protein; sars cov data; rna cells using; mice sars infection; cells cell virus file(s): https://doi.org/10.1101/2020.06.30.177097, https://doi.org/10.1101/2019.12.26.888511, https://doi.org/10.1101/2020.08.11.245068, https://doi.org/10.1101/2020.06.30.180927, https://doi.org/10.1101/2020.10.05.326850 titles(s): Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM | Neurophysiological Correlates of the Dunning-Kruger Effect | Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus | Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury | Taxonomic revision of the threatened African genus Pseudohydrosme Engl. (Araceae), with P. ebo, a new, Critically Endangered species from Ebo, Cameroon Type: cord title: journal-biorxiv-cord date: 2021-05-30 time: 16:05 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: facet_journal:"bioRxiv" ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-347714-vxxhglx7 author: Abitogun, Folagbade title: COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding date: 2020-10-14 words: 3707.0 sentences: 191.0 pages: flesch: 44.0 cache: ./cache/cord-347714-vxxhglx7.txt txt: ./txt/cord-347714-vxxhglx7.txt summary: (10, 11) The structure of the spike glycoprotein of the virus is also an extended similarity with SARS-CoV, (4) which together with COVID19: Exploring uncommon epitopes for a stable immune response through MHC1 binding other proteins of the virus are candidates for vaccine development and are being explored in different settings due to the active roles of the proteins in the infectivity of the virus. (18) However studies have shown that full length spike protein vaccines for SARS-CoV may lead to antibody mediated disease enhancement causing inflammatory and liver damage in animal models (19, 20) which is why in this manuscript, we applied immuno-informatics "in silico" approaches to identify potential CD8+ cytotoxic T Cell epitopes from proteins of SARS-CoV-2, SARS-CoV and MERS-CoV. Multi-epitope Based Peptide Vaccine Design Using Three Structural Proteins (S, E, and M) of SARS-CoV-2: An In Silico Approach abstract: The COVID19 pandemic has resulted in 1,092,342 deaths as of 14th October 2020, indicating the urgent need for a vaccine. This study highlights novel protein sequences generated by shot gun sequencing protocols that could serve as potential antigens in the development of novel subunit vaccines and through a stringent inclusion criterion, we characterized these protein sequences and predicted their 3D structures. We found distinctly antigenic sequences from the SARS-CoV-2 that have led to identification of 4 proteins that demonstrate an advantageous binding with Human leukocyte antigen-1 molecules. Results show how previously unexplored proteins may serve as better candidates for subunit vaccine development due to their high stability and immunogenicity, reinforce by their HLA-1 binding propensities and low global binding energies. This study thus takes a unique approach towards furthering the development of vaccines by employing multiple consensus strategies involved in immuno-informatics technique. url: https://doi.org/10.1101/2020.10.14.339689 doi: 10.1101/2020.10.14.339689 id: cord-315982-iuez41zj author: Achdout, Hagit title: COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning date: 2020-10-30 words: 4103.0 sentences: 223.0 pages: flesch: 54.0 cache: ./cache/cord-315982-iuez41zj.txt txt: ./txt/cord-315982-iuez41zj.txt summary: title: COVID Moonshot: Open Science Discovery of SARS-CoV-2 Main Protease Inhibitors by Combining Crowdsourcing, High-Throughput Experiments, Computational Simulations, and Machine Learning Herein we provide a living summary of the data generated during the COVID Moonshot project focused on the development of SARS-CoV-2 main protease (Mpro) inhibitors. The COVID Moonshot project has focused on progressing early fragment-screening results into potent compounds with activity against both the main protease and the virus. The rationales for each design include docking-based approaches, by-eye structure-based designs, machine learning approaches, crawling of the past literature on SARS and MERS compounds, and other general medicinal-chemistry insights that can be visualised at https://postera.ai/covid. At 24 h post-seeding, cell culture medium was discarded, cells were washed twice with PBS and infected with SARS-CoV-2 at an MOI of 0.01 in the presence of six concentrations of the inhibitors (25 M -0.06 M). abstract: Herein we provide a living summary of the data generated during the COVID Moonshot project focused on the development of SARS-CoV-2 main protease (Mpro) inhibitors. Our approach uniquely combines crowdsourced medicinal chemistry insights with high throughput crystallography, exascale computational chemistry infrastructure for simulations, and machine learning in triaging designs and predicting synthetic routes. This manuscript describes our methodologies leading to both covalent and non-covalent inhibitors displaying protease IC50 values under 150 nM and viral inhibition under 5 uM in multiple different viral replication assays. Furthermore, we provide over 200 crystal structures of fragment-like and lead-like molecules in complex with the main protease. Over 1000 synthesized and ordered compounds are also reported with the corresponding activity in Mpro enzymatic assays using two different experimental setups. The data referenced in this document will be continually updated to reflect the current experimental progress of the COVID Moonshot project, and serves as a citable reference for ensuing publications. All of the generated data is open to other researchers who may find it of use. url: https://doi.org/10.1101/2020.10.29.339317 doi: 10.1101/2020.10.29.339317 id: cord-103448-xa5zgkd3 author: Adachi, Hiroaki title: Jurassic NLR: conserved and dynamic evolutionary features of the atypically ancient immune receptor ZAR1 date: 2020-10-12 words: 9758.0 sentences: 484.0 pages: flesch: 48.0 cache: ./cache/cord-103448-xa5zgkd3.txt txt: ./txt/cord-103448-xa5zgkd3.txt summary: The phylogenetic tree was generated in MEGA7 by the neighbour-joining method using NB-ARC domain sequences of ZAR1-like proteins identified from the prior BLAST searches and 1019 NLRs identified from 6 representative plant species, taro, stout camphor, columbine, tomato, sugar beet and Arabidopsis. The overall conservation of the 120 ZAR1 orthologs enabled us to perform phylogenetic analyses using the full-length protein sequence and not just the NB-ARC domain as generally done with NLRs ( ZAR1 phylogenetic tree with well-supported branches that generally mirrored established phylogenetic relationships between the examined plant species (Smith and Brown, 2018; Chaw et al., 2019) . Taken together, based on the conserved motifs depicted in Figure 3A , we propose that angiosperm ZAR1 orthologs share the main functional features of Arabidopsis ZAR1: 1) effector recognition via RLCK binding, 2) remodelling of intramolecular interactions via ADP/ATP switch, 3) oligomerisation via the NBD-NBD interface and 4) α1 helix/MADA motifmediated activation of hypersensitive cell death. abstract: NLR immune receptors form one of the most diverse protein families in flowering plants (angiosperms). NLRs have massively expanded through birth-and-death evolution and typically exhibit hallmarks of rapid evolution even at the intraspecific level. Here, we reconstructed the evolutionary history of ZAR1, an atypically conserved NLR that traces its origin to early angiosperm lineages ~220 to 150 million years ago (Jurassic period). We used iterative sequence similarity searches coupled with phylogenetic analyses to determine the degree to which ZAR1 orthologs and paralogs occur in plants. We discovered 120 ZAR1 orthologs in 88 species, including the monocot Colacasia esculenta, the magnoliid Cinnamomum micranthum and the majority of eudicots, notably the early diverging eudicot species Aquilegia coerulea. Analyses of the ortholog sequences revealed highly conserved features of ZAR1, including regions for pathogen effector recognition, intramolecular interactions and cell death activation. This also uncovered a new conserved surface on the underside of the activated ZAR1 resistosome wheel. Throughout its evolution, ZAR1 also acquired novel features. Nine ZAR1 orthologs from cassava and cotton carry an integrated thioredoxin-like domain at their C-termini. ZAR1 also duplicated into two paralog families ZAR1-SUB and ZAR1-CIN. ZAR1-SUB, which emerged in the eudicots, is a large class of sequence diverse ZAR1 paralogs that lack several of the conserved motifs of ZAR1. A second family, ZAR1-CIN, comprises an expansion of 11 paralogs unique to a ~500 kb locus in the C. micranthum genome and located about 48 Mb from ZAR1. We conclude that ZAR1 stands out among angiosperm NLRs for having an ancient origin and having experienced relatively limited gene duplication and expansion throughout its deep evolutionary history. Nonetheless, ZAR1 did also give rise to non-canonical NLR proteins with integrated domains and degenerated molecular features. url: https://doi.org/10.1101/2020.10.12.333484 doi: 10.1101/2020.10.12.333484 id: cord-102595-3lbrfsrh author: Adam, Kirsten C.S. title: Steady-state visually evoked potentials and feature-based attention: Pre-registered null results and a focused review of methodological considerations date: 2020-10-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Feature-based attention is the ability to selectively attend to a particular feature (e.g., attend to red but not green items while looking for the ketchup bottle in your refrigerator), and steady-state visually evoked potentials (SSVEPs) measured from the human electroencephalogram (EEG) signal have been used to track the neural deployment of feature-based attention. Although many published studies suggest that we can use trial-by-trial cues to enhance relevant feature information (i.e., greater SSVEP response to the cued color), there is ongoing debate about whether participants may likewise use trial-bytrial cues to voluntarily ignore a particular feature. Here, we report the results of a preregistered study in which participants either were cued to attend or to ignore a color. Counter to prior work, we found no attention-related modulation of the SSVEP response in either cue condition. However, positive control analyses revealed that participants paid some degree of attention to the cued color (i.e., we observed a greater P300 component to targets in the attended versus the unattended color). In light of these unexpected null results, we conducted a focused review of methodological considerations for studies of feature-based attention using SSVEPs. In the review, we quantify potentially important stimulus parameters that have been used in the past (e.g., stimulation frequency; trial counts) and we discuss the potential importance of these and other task factors (e.g., feature-based priming) for SSVEP studies. url: https://doi.org/10.1101/2020.08.31.275602 doi: 10.1101/2020.08.31.275602 id: cord-103396-jiuqk6kg author: Adler, Paul N. title: Short distance non-autonomy and intercellular transfer of chitin synthase in Drosophila date: 2020-05-26 words: 4072.0 sentences: 246.0 pages: flesch: 63.0 cache: ./cache/cord-103396-jiuqk6kg.txt txt: ./txt/cord-103396-jiuqk6kg.txt summary: In experiments where we imaged Kkv::NG in living pupae we noticed fluorescent puncta in the 219 extracellular space between the pupal cuticle and the epidermal cells that were in the process of 220 synthesizing the adult cuticle (Fig. 6BC ). No fluorescence was observed in the region 227 between the pupal cuticle and the apical surface of the epithelial cells in Ore-R pupae (Fig. 6EF) . We also observed puncta in very young pupae (20 237 hr awp) prior to the detachment of the epithelial cells from the pupal cuticle (Fig. S6B) . These animals showed a large 253 number of fluorescent puncta present in the space between the pupal cuticle and the apical surface of 254 the epithelial cells ( Fig 6GHI) . However, in carrying out these in vivo imaging experiments we observed that the autofluorescence of 259 the thoracic and abdominal pupal cuticles was quite distinct (Fig S8) . abstract: The complex structure of insect exoskeleton has inspired material scientists and engineers. Chitin is a major component of the cuticle and it is synthesized by the enzyme chitin synthase. There is a single chitin synthase gene (kkv) in Drosophila facilitating research on the function of chitin. Previous editing of kkv lead to the recovery of a viable hypomorphic allele. Experiments described in this paper argue that a reduction in chitin synthase leads to the shafts of sensory bristles becoming fragile and frequently breaking off as the animals age. This is likely due to reduced chitin levels and further suggests that chitin plays a role in resilience of insect cuticle. The different layers in cuticle are continuous across the many epidermal cells that secrete the cuticle that covers the body. Little is known about the mechanisms responsible for this continuity. Using genetic mosaics and scanning electron microscopy this paper establishes that kkv shows short range cell non-autonomy. It also provides evidence for 2 possible mechanisms. One is the intercellular transfer of Kkv protein from one cell to its neighbors and the second is the deposition of cuticular material across the boundaries of neighboring cells. url: https://doi.org/10.1101/2020.05.24.113803 doi: 10.1101/2020.05.24.113803 id: cord-336343-qbcb9qi3 author: Agarwal, Ajay title: in-silica Analysis of SARS-CoV-2 viral strain using Reverse Vaccinology Approach: A Case Study for USA date: 2020-06-16 words: 2332.0 sentences: 154.0 pages: flesch: 56.0 cache: ./cache/cord-336343-qbcb9qi3.txt txt: ./txt/cord-336343-qbcb9qi3.txt summary: Using in-silica analysis and reverse vaccinology, two leader proteins were identified to be potential vaccine candidates for development of a multi-epitope drug. This study aims to utilize a reverse-vaccinology approach in order to identify potential vaccine candidates for COVID19 for the country USA. For MHC Class-I T-cell epitope prediction for ORF1ab leader proteins, NetMHCpan EL 4.0 method was used. The T-cell epitopes of the MHC Class-I for both the leader protein were determined using the NetMHCpan EL 4.0 prediction method of the IEDB server keeping the sequence length at 9. For MHC class-II, T-cell epitopes (HLA DRB1*04-01 allele) of the proteins were also determined using the IEDB Analysis tools. The potential T-cell epitopes, whose topology, antigenicity, allergenicity, toxicity and conservancy was analysed, for ORF1ab leader proteins MT326102 and MT326175 are depicted in the following tables. Out of the two MHC Class-I epitopes selected for leader proteins ORF1ab MT326102 and MT326175, the global energy was lowest for LSLPVLQVR. abstract: The recent pandemic of COVID19 that has struck the world is yet to be battled by a potential cure. Countless lives have been claimed due to the existing pandemic and the societal normalcy has been damaged permanently. As a result, it becomes crucial for academic researchers in the field of bioinformatics to combat the existing pandemic. The study involved collecting the virulent strain sequence of SARS-nCoV19 for the country USA against human host through publically available bioinformatics databases. Using in-silica analysis and reverse vaccinology, two leader proteins were identified to be potential vaccine candidates for development of a multi-epitope drug. The results of this study can provide further researchers better aspects and direction on developing vaccine and immune responses against COVID19. This work also aims at promoting the use of existing bioinformatics tools to faster streamline the pipeline of vaccine development. The Situation of COVID19 A new infection respiratory disease was first observed in the month of December 2019, in Wuhan, situated in the Hubei province, China. Studies have indicated that the reason of this disease was the emergence of a genetically-novel coronavirus closely related to SARS-CoV. This coronavirus, now named as nCoV-19, is the reason behind the spread of this fatal respiratory disease, now named as COVID-19. The initial group of infections is supposedly linked with the Huanan seafood market, most likely due to animal contact. Eventually, human-to-human interaction occurred and resulted in the transmission of the virus to humans. [13]. Since then, nCoV-19 has been rapidly spreading within China and other parts of World. At the time of writing this article (mid-March 2020), COVID-19 has spread across 146 countries. A count of 164,837 cases have been confirmed of being diagnosed with COVID-19, and a total of 6470 deaths have occurred. The cumulative cases have been depicting a rising trend and the numbers are just increasing. WHO has declared COVID-19 to be a “global health emergency”. [14]. Current Scenario and Objectives Currently, research is being conducted on a massive level to understand the immunology and genetic characteristics of the disease. However, no cure or vaccine of nCoV-19 has been developed at the time of writing this article. Though, nCoV-19 and SARS-CoV are almost genetically similar, the respiratory syndrome caused by both of them, COVID-19 and SARS respectively, are completely different. Studies have indicated that – “SARS was more deadly but much less infectious than COVID-19”. -World Health Organization url: https://doi.org/10.1101/2020.06.16.154559 doi: 10.1101/2020.06.16.154559 id: cord-102720-ka95resa author: Aguilar, César title: Convergent evolution of Streptomyces protease inhibitors involving a tRNA-mediated condensation-minus NRPS date: 2020-10-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Small peptide aldehydes (SPAs) with protease inhibitory activity are natural products typically synthesized by nonribosomal peptide synthetases (NRPS). SPAs are widely used in biotechnology, as therapeutic agents, they are physiologically relevant and regulate development of the natural hosts. During genome evolutionary analysis of Streptomyces lividans 66 we identified an NRPS-like biosynthetic gene cluster (BGC) that lacked a condensation (C) domain but included a tRNA-Utilizing Enzyme (tRUE) belonging to the leucyl/phenylalanyl (L/F) transferase family. This system was predicted to direct the synthesis of a novel SPA with protease inhibitory activity, called livipeptin. Following genome mining and phylogenomic analyses we confirmed the presence of tRUEs within diverse Streptomyces genomes, including fusions with a C-minus NRPS-like protein. We further demonstrate functional cooperation between these enzymes and provide the biosynthetic rules for the synthesis of livipeptin, expanding the known universe of acetyl-leu/phe-arginal SPAs. The L/F-transferase C-minus NRPS productive interaction was shown to be tRNA-dependent after semisynthetic assays in the presence of RNAse, which contrasts with leupeptin, an acetyl-leu-arginal SPA that we show to be produced by Streptomyces roseous ATCC 31245 via a tRUE-minus BGC with multiple complete NRPSs. Thus, livipeptin and leupeptin are the result of convergent evolution, which has driven the appearance of unprecedented biosynthetic logics directing the synthesis of protease inhibitors thought to be at the core of Streptomyces colony biology. Our results pave the way for understanding this Streptomyces trait, as well as for the discovery of novel natural products following evolutionary genome mining approaches. Abstract importance Convergent evolution in microbiology is believed to be highly recurrent yet examples that have been comprehensively characterized are scarce. Proteases inhibition by small peptide aldehydes is at the core of many microbiological processes, both within the cell and during colony development, and in microbial ecology. Here we report the biosynthetic foundations of leupeptin, the main Streptomyces protease inhibitor, and of livipeptin, a protease inhibitor produced by Streptomyces lividans. Although these peptides belong to the same chemical class, here we show that their biosynthetic routes result from convergent evolution, as they involve unrelated biosynthetic mechanisms, including the recruitment of a tRNA-utilizing enzyme that functionally replaces the condensation domain of a nonribosomal peptide synthetase during livipeptin biosynthesis. Thus, these results pave the way for understanding Streptomyces protease inhibitors as a trait and provide unprecedented knowledge for genome mining of natural products and synthetic biology where proteases inhibition is desirable. url: https://doi.org/10.1101/2020.10.26.356543 doi: 10.1101/2020.10.26.356543 id: cord-333089-ufyzqgqk author: Aguilar-Pineda, Jorge Alberto title: Structural and functional analysis of female sex hormones against SARS-Cov2 cell entry date: 2020-07-29 words: 6957.0 sentences: 359.0 pages: flesch: 51.0 cache: ./cache/cord-333089-ufyzqgqk.txt txt: ./txt/cord-333089-ufyzqgqk.txt summary: Based on the structural complementarity and steric impediments between the S protein and human ACE2 (hACE2) protein membranes, we mapped the glycosylation sites of both models [21] [22] [23] [24] and performed molecular dynamics simulations (MDS) by 250 ns to stabilize the glycosylated SARS-CoV2 spike (S) and hACE2 complex (suppl. Given the possibility that occupancy at glycosylated residues or S-RBD binding sites by estrogens could modify the affinity of the SARS-CoV2 virus and alter entry into the cell thereby reducing infectivity, we sought to further examine these interactions using a range of complementary experimental approaches (see Table S1 ). In an effort to explore the potential protective effects of female sex hormones against SARS-CoV-2 infection, we examined the impact of estradiol (17β-diol) and a dietary-derived phytoestrogen (S-equol) on hACE2 structure and protein expression by a combination of in silico modeling, in vitro, and in vivo analysis. abstract: Emerging evidence suggests that males are more susceptible to severe infection by the SARS-CoV-2 virus than females. A variety of mechanisms may underlie the observed gender-related disparities including differences in sex hormones. However, the precise mechanisms by which female sex hormones may provide protection against SARS-CoV-2 infectivity remains unknown. Here we report new insights into the molecular basis of the interactions between the SARS-CoV-2 spike (S) protein and the human ACE2 receptor. We further observed that glycosylation of the ACE2 receptor enhances SARS-CoV-2 infectivity. Importantly estrogens can disrupt glycan-glycan interactions and glycan-protein interactions between the human ACE2 and the SARS-CoV2 thereby blocking its entry into cells. In a mouse model, estrogens reduced ACE2 glycosylation and thereby alveolar uptake of the SARS-CoV-2 spike protein. These results shed light on a putative mechanism whereby female sex hormones may provide protection from developing severe infection and could inform the development of future therapies against COVID-19. url: https://doi.org/10.1101/2020.07.29.227249 doi: 10.1101/2020.07.29.227249 id: cord-103528-3tib5o1m author: Ahmed, Asad title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity date: 2020-09-28 words: 3798.0 sentences: 242.0 pages: flesch: 54.0 cache: ./cache/cord-103528-3tib5o1m.txt txt: ./txt/cord-103528-3tib5o1m.txt summary: title: DEELIG: A Deep Learning-based approach to predict protein-ligand binding affinity Here, we have incorporated Convolutional Neural Networks that find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies towards a diverse set of ligands. Initial raw data database created contained protein structures in PDB format, protein sequences in FASTA format, ligand in SDF format and binding affinity values of corresponding protein-ligand pairs for 5464 complexes. We propose a deep-learning based approach to predict ligand (eg., drug)-target binding affinity using only structures of target protein (PDB format) and ligand (SDF format) as inputs. We have trained two models to predict the binding affinity between protein and ligand in a given complex. We have constructed a novel dataset that represents a diverse set of ligands and using a novel deep learning based approach we have achieved significant improvement in prediction of binding affinity of protein-ligand complexes. abstract: Protein-ligand binding prediction has extensive biological significance. Binding affinity helps in understanding the degree of protein-ligand interactions and has wide protein applications. Protein-ligand docking using virtual screening and molecular dynamic simulations are required to predict the binding affinity of a ligand to its cognate receptor. In order to perform such analyses, it requires intense computational power and it becomes impossible to cover the entire chemical space of small molecules. It has been aided by a shift towards using Machine Learning-based methodologies that aids in binding prediction using regression. Recent developments using deep learning has enabled us to make sense of massive amounts of complex datasets. Herein, the ability of the model to “learn” intrinsic patterns in a complex plane of data is the strength of the approach. Here, we have incorporated Convolutional Neural Networks that find spatial relationships among data to help us predict affinity of binding of proteins in whole superfamilies towards a diverse set of ligands. The models were trained and validated using a detailed methodology for feature extraction. We have also tested DEELIG on protein complexes relevant to the current public health scenario. Our approach to network construction and training on protein-ligand dataset prepared in-house has provided significantly better results than previously existing methods in the field. url: https://doi.org/10.1101/2020.09.28.316224 doi: 10.1101/2020.09.28.316224 id: cord-290445-vb53bih9 author: Ahmed, Shiek SSJ title: Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery date: 2020-04-23 words: 3793.0 sentences: 208.0 pages: flesch: 42.0 cache: ./cache/cord-290445-vb53bih9.txt txt: ./txt/cord-290445-vb53bih9.txt summary: Secondly, the viral replication machinery network from SET-B with 332 seed proteins extended to 1486 neighboring proteins with 11438 interacting edges which representing the mechanism attributed to evasion of the SARS-CoV2 genome into the host. Similarly, the viral replication machinery network was acquired with 1522 proteins with 9747 interacting edges showing the complex SARS-CoV-2 mechanism in the human lungs. These common molecules represent the inter-connecting mechanism involved in the transcription machinery, immune response, cell growth and/or maintenance, transport, metabolism, protein metabolism, cell communication and signal transduction that activated upon virus binding and has been subsequently utilized for viral replication process (S5 Table) Also mapping with other viral infection dataset, 50 hub proteins of the replication machinery network have noticed in influenza virus infection (S4 Table) , which suggests SARS-CoV2 and influenza may have a similar mode of host infection machinery [17] . The molecular pathways of interconnecting protein hubs could be the intermediate phase that connects the receptor activation mechanism and viral replication process (Fig 10) . abstract: We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2. url: https://doi.org/10.1101/2020.04.20.050138 doi: 10.1101/2020.04.20.050138 id: cord-297754-d4xnj551 author: Aktas, Emre title: Bioinformatic Analysis Reveals That Some Mutations May Affect On Both Spike Structure Damage and Ligand Binding Site date: 2020-09-03 words: 2891.0 sentences: 346.0 pages: flesch: 75.0 cache: ./cache/cord-297754-d4xnj551.txt txt: ./txt/cord-297754-d4xnj551.txt summary: It might be thought like case of influenza(where mutations slowly accumulate in the hemagglutinin protein during a flu season),and there is a complex interplay between mutations that can confer immune resistance to the virus, and the fitness landscape of the particular variant in which they arise [5] .The SARS-CoV-2 ,which mutation rate rate remarkable high and many variation have already characterized, has shown to have gone through certain mutations both in its structural and non structural proteins within several months while spreading throughout the world [8, 10] I focused my study on both determining some mutations that occurred based on the regions and evaluating whether this new mutation had an effect on the shapes of spike proteins.Besides I tried to predict that how mutations affect on ligand site. abstract: There are some mutations are known related to SARS-CoV-2. Together with these mutations known, I tried to show other newly mutations regionally. According to my results which 4326 whole sequences are used, I found that some mutations occur only in a certain region, while some other mutations are found in each regions. Especially in Asia, more than one mutation(three different mutations are found in QLA46612 isolated from South Korea) was seen in the same sequence. Although I detected a huge number of mutations (more than seventy in Asia) by regions, some of them were predicted that damage spike’s protein structure by using bioinformatic tools.The predicted results are G75V(isolated from North America), T95I(isolated from South Korea), G143V(isolated from North America), M177I(isolated Asia), L293M(isolated from Asia), P295H(isolated from Asia), T393P(isolated from Europe), P507S(isolated from Asia), D614G(isolated from all regions) respectively. Also, in this study, I tried to show how possible binding sites of ligands change if the spike protein structure is damaged and whether more than one mutation affects ligand binding was estimated using bioinformatics tools. Interestingly, mutations that predicted to damage the structure do not affect ligand binding sites, whereas ligands’ binding sites were affected in those with multiple mutations.Focusing on mutations may opens up the window to exploit new future therapeutic targets. url: https://doi.org/10.1101/2020.08.10.244632 doi: 10.1101/2020.08.10.244632 id: cord-330384-yujbcwg5 author: Al-Mulla, Fahd title: A comprehensive germline variant and expression analyses of ACE2, TMPRSS2 and SARS-CoV-2 activator FURIN genes from the Middle East: Combating SARS-CoV-2 with precision medicine date: 2020-05-16 words: 4684.0 sentences: 249.0 pages: flesch: 52.0 cache: ./cache/cord-330384-yujbcwg5.txt txt: ./txt/cord-330384-yujbcwg5.txt summary: The increased cleavage activity of this protease was suggested to diminish viral recognition by neutralizing antibodies and by activating SARS spike (S) protein for virus-cell fusion 11 and facilitates the active binding of SARS-CoV-2 through ACE2 receptor, which is a risk factor for a more serious COVID-19 presentation [8] [9] [10] . Recent studies, assessed the genetic variations and eQTL (expression quantitative trait locus) expression profiles in the candidate genes ACE2, TMPRSS2, and FURIN to demonstrate the sex and population-wise differences that may influence the pathogenicity of SARS-CoV-2 9, [15] [16] [17] [18] [19] . Therefore, we screened the genetic variations and eQTL expression of the SARS-CoV-2 candidate genes, ACE2, TMPRSS2 and FURIN in three Middle Eastern populations: Kuwaiti, Iranian, and Qatari and compared them to available MAF data in the gnomAD database 41 . abstract: The severity of the new COVID-19 pandemic caused by the SARS-CoV-2 virus is strikingly variable in different global populations. SARS-CoV-2 uses ACE2 as a cell receptor, TMPRSS2 protease, and FURIN peptidase to invade human cells. Here, we investigated 1,378 whole-exome sequences of individuals from the Middle Eastern populations (Kuwait, Qatar, and Iran) to explore natural variations in the ACE2, TMPRSS2, and FURIN genes. We identified two activating variants (K26R and N720D) in the ACE2 gene that are more common in Europeans than in the Middle Eastern, East Asian, and African populations. We postulate that K26R can activate ACE2 and facilitate binding to S-protein RBD while N720D enhances TMPRSS2 cutting and, ultimately, viral entry. We also detected deleterious variants in FURIN that are frequent in the Middle Eastern but not in the European populations. This study highlights specific genetic variations in the ACE2 and FURIN genes that may explain SARS-CoV-2 clinical disparity. We showed structural evidence of the functionality of these activating variants that increase the SARS-CoV-2 aggressiveness. Finally, our data illustrate a significant correlation between ACE2 variants identified in people from Middle Eastern origins that can be further explored to explain the variation in COVID-19 infection and mortality rates globally. url: https://doi.org/10.1101/2020.05.16.099176 doi: 10.1101/2020.05.16.099176 id: cord-102766-n6mpdhyu author: Alam, Md. Nafis Ul title: Short k-mer Abundance Profiles Yield Robust Machine Learning Features and Accurate Classifiers for RNA Viruses date: 2020-06-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: High throughout sequencing technologies have greatly enabled the study of genomics, transcriptomics and metagenomics. Automated annotation and classification of the vast amounts of generated sequence data has become paramount for facilitating biological sciences. Genomes of viruses can be radically different from all life, both in terms of molecular structure and primary sequence. Alignment-based and profile-based searches are commonly employed for characterization of assembled viral contigs from high-throughput sequencing data. Recent attempts have highlighted the use of machine learning models for the task but these models rely entirely on DNA genomes and owing to the intrinsic genomic complexity of viruses, RNA viruses have gone completely overlooked. Here, we present a novel short k-mer based sequence scoring method that generates robust sequence information for training machine learning classifiers. We trained 18 classifiers for the task of distinguishing viral RNA from human transcripts. We challenged our models with very stringent testing protocols across different species and evaluated performance against BLASTn, BLASTx and HMMER3 searches. For clean sequence data retrieved from curated databases, our models display near perfect accuracy, outperforming all similar attempts previously reported. On de-novo assemblies of raw RNA-Seq data from cells subjected to Ebola virus, the area under the ROC curve varied from 0.6 to 0.86 depending on the software used for assembly. Our classifier was able to properly classify the majority of the false hits generated by BLAST and HMMER3 searches on the same data. The outstanding performance metrics of our model lays the groundwork for robust machine learning methods for the automated annotation of sequence data. Author Summary In this age of high-throughput sequencing, proper classification of copious amounts of sequence data remains to be a daunting challenge. Presently, sequence alignment methods are immediately assigned to the task. Owing to the selection forces of nature, there is considerable homology even between the sequences of different species which draws ambiguity to the results of alignment-based searches. Machine Learning methods are becoming more reliable for characterizing sequence data, but virus genomes are more variable than all forms of life and viruses with RNA-based genomes have gone overlooked in previous machine learning attempts. We designed a novel short k-mer based scoring criteria whereby a large number of highly robust numerical feature sets can be derived from sequence data. These features were able to accurately distinguish virus RNA from human transcripts with performance scores better than all previous reports. Our models were able to generalize well to distant species of viruses and mouse transcripts. The model correctly classifies the majority of false hits generated by current standard alignment tools. These findings strongly imply that this k-mer score based computational pipeline forges a highly informative, rich set of numerical machine learning features and similar pipelines can greatly advance the field of computational biology. url: https://doi.org/10.1101/2020.06.25.170779 doi: 10.1101/2020.06.25.170779 id: cord-353877-wzndpcq3 author: Albagi, Sahar Obi Abd title: A Multiple Peptides Vaccine against nCOVID-19 Designed from the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics Approach date: 2020-05-20 words: 3747.0 sentences: 264.0 pages: flesch: 58.0 cache: ./cache/cord-353877-wzndpcq3.txt txt: ./txt/cord-353877-wzndpcq3.txt summary: Due to the current COVID-19 pandemic, the rapid discovery of a safe and effective vaccine is an essential issue, consequently, this study aims to predict potential COVID-19 peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. Consistent with global efforts, this study aims to predict potential COVID-19 Peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. The molecular docking results showed that the Spike peptide FTISVTTEI has the lowest docking energy score with the MHC I HLA-B1503 allele, hence it is predicted to have the highest binding affinity. Regarding the interaction with the MHC II molecule, the Spike peptide EVFNATRFASVYAWN showed the lowest docking energy score with the three MHC II alleles HLA-DPA1*01:03/DPB1*02:01, HLA-DQA1*01:02/DQB1*06:02, and HLA-DRB1, hence it is predicted to have the highest binding affinity to the three alleles. abstract: Due to the current COVID-19 pandemic, the rapid discovery of a safe and effective vaccine is an essential issue, consequently, this study aims to predict potential COVID-19 peptide-based vaccine utilizing the Nucleocapsid phosphoprotein (N) and Spike Glycoprotein (S) via the Immunoinformatics approach. To achieve this goal, several Immune Epitope Database (IEDB) tools, molecular docking, and safety prediction servers were used. According to the results, The Spike peptide peptides SQCVNLTTRTQLPPAYTNSFTRGVY is predicted to have the highest binding affinity to the B-Cells. The Spike peptide FTISVTTEI has the highest binding affinity to the MHC I HLA-B1503 allele. The Nucleocapsid peptides KTFPPTEPK and RWYFYYLGTGPEAGL have the highest binding affinity to the MHC I HLA-A0202 allele and the three MHC II alleles HLA-DPA1*01:03/DPB1*02:01, HLA-DQA1*01:02/DQB1- *06:02, HLA-DRB1, respectively. Furthermore, those peptides were predicted as non-toxic and non-allergen. Therefore, the combination of those peptides is predicted to stimulate better immunological responses with respectable safety. url: https://doi.org/10.1101/2020.05.20.106351 doi: 10.1101/2020.05.20.106351 id: cord-103735-nil1vv6h author: Alfano, Niccolo title: Non-invasive surveys of mammalian viruses using environmental DNA date: 2020-03-29 words: 5829.0 sentences: 373.0 pages: flesch: 53.0 cache: ./cache/cord-103735-nil1vv6h.txt txt: ./txt/cord-103735-nil1vv6h.txt summary: Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. In filtered water and sediment samples collected from the same waterhole, only one virus per sample was generally identified and in one location (WM20 and SM20) contigs from different viral families were isolated based on sample type. We provide evidence that environmental and invertebrate-derived DNA samples including waterhole water, sediment and wild haematophagous terrestrial leeches can be used to survey known and unknown viruses. abstract: Environmental DNA (eDNA) and its subdiscipline, invertebrate-derived DNA (iDNA) have been used to survey biodiversity non-invasively [1,2]. Water is ubiquitous in most ecosystems, and, among invertebrates, terrestrial haematophagous leeches are abundant and can be easily collected in many tropical rainforests [3,4]. Such non-invasive nucleic acid sources can mitigate difficulties of obtaining wildlife samples, particularly in remote areas or for rare species. Recently, eDNA/iDNA sources have been applied to monitoring specific wildlife pathogens [5,6]. However, previous studies have focused on known pathogens, whereas most wildlife pathogens are uncharacterized and unknown. Non-invasive approaches to monitoring known and novel pathogens may be of particular benefit in ecosystems prone to viral emergence, many of which occur in areas where invasive sampling is challenging, such as tropical rainforests. Here, we show that both eDNA from natural waterholes, and iDNA from terrestrial haematophagous leeches, can be used to detect unknown viruses circulating in mammalian hosts (Figure 1). Using a curated set of RNA oligonucleotides based on the ViroChip microarray assay [7] as baits in a hybridization capture system, multiple mammalian RNA and DNA viruses were detected from both eDNA and iDNA samples. Congruence was found between host DNA assignment and viruses identified in leeches, and between animals observed visiting the waterholes and the viruses detected. Our results demonstrate that eDNA/iDNA samples may represent an effective non-invasive resource for studying wildlife viral diversity. Several of the detected viruses were novel, highlighting the potential of eDNA/iDNA for epidemiological analysis of emerging viruses prior to their emergence. Highlights Environmental DNA (water and blood-sucking leeches) provided a non-invasive method of screening wildlife for viruses A comprehensive viral RNA oligonucleotide bait set was developed to capture known and unknown mammalian virus diversity Leech blood meal host determination and viruses identified were congruent Viruses determined from water correlated with known and observed species visiting the water sources In brief Alfano, Dayaram, et al. demonstrate that environmental DNA from southeast Asian leech bloodmeals and waterholes from Africa and Mongolia can be used as to detect viruses circulating in wildlife. These nucleic acid sources may represent an effective non-invasive resource for studying wildlife viral diversity and emerging viruses pre-emergence. url: https://doi.org/10.1101/2020.03.26.009993 doi: 10.1101/2020.03.26.009993 id: cord-344236-qp3ianzf author: Ali, Fedaa title: ACE2 coding variants in different populations and their potential impact on SARS-CoV-2 binding affinity date: 2020-05-08 words: 2465.0 sentences: 163.0 pages: flesch: 54.0 cache: ./cache/cord-344236-qp3ianzf.txt txt: ./txt/cord-344236-qp3ianzf.txt summary: Classical electrostatic calculations based on solving Poisson-Boltzmann (PB) equation is used to investigate the interaction energies between SARS-CoV-2 and ACE2 for different mutated ACE2 structures. In an attempt to better understand the susceptibility of different populations to infection by SARS-CoV-2, we gathered data on ACE2 missense variants from different projects and databases that aggregate allele frequencies (AF). These projects and databases included Single Nucleotide Polymorphism Database (dbSNP) 12, 13 , 1000 genomes project phase 3 (1KGP3) 14 , Allele Frequency Aggregator (ALFA project) a , Exome Aggregation Consortium (ExAC) 15 SARS-CoV-2 was reported to bind to human ACE2 via different ACE2 residues; Q24, D30, H34, Y41, Q42, M82, K353 and R357 5 . The electrostatic and the van der Waal contribution to the interaction energies of SARS-CoV-2/ACE2 were compared between single mutated and WT protein at pH =7 (Table 1 ). abstract: The susceptibility of different populations to the SARS-CoV-2 infection is not yet understood. A deeper analysis of the genomes of individuals from different populations might explain their risk for infection. In this study, a combined analysis of ACE2 coding variants in different populations and computational chemistry calculations are conducted in order to probe the potential effects of ACE2 coding variants on SARS-CoV-2/ACE2 binding affinity. Our study reveals novel interaction data on the variants and SARS-CoV-2. We could show that ACE2-K26R; which is more frequent in the Ashkenazi Jewish population decrease the electrostatic attraction between SARS-CoV-2 and ACE2. On the contrary, ACE2-I468V, R219C, K341R, D206G, G211R were found to increase the electrostatic attraction and increase the binding to SARS-CoV-2; ordered by the strength of binding from weakest to strongest. I468V, R219C, K341R, D206G and G211R were more frequent in East Asian, South Asian, African and African American, European and European and South Asian populations, respectively. SARS-CoV-2/ACE2 interface in the WT protein and corresponding variants is showed to be a dominated by van der Waals (vdW) interactions. All the mutations except K341R induce an increase in the vdW attractions between the ACE2 and the SARS-CoV-2. The largest increase of is observed for the R219C mutant. url: https://doi.org/10.1101/2020.05.08.084384 doi: 10.1101/2020.05.08.084384 id: cord-102481-obig3mu1 author: Alić, Ivan title: “Patient-specific Alzheimer-like pathology in trisomy 21 cerebral organoids reveals BACE2 as a gene-dose-sensitive AD-suppressor in human brain” date: 2020-01-31 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A population of >6 million people worldwide at high risk of Alzheimer’s disease (AD) are those with Down Syndrome (DS, caused by trisomy 21 (T21)), 70% of whom develop dementia during lifetime, caused by an extra copy of β-amyloid-(Aβ)-precursor-protein gene. We report AD-like pathology in cerebral organoids grown in vitro from non-invasively sampled strands of hair from 71% of DS donors. The pathology consisted of extracellular diffuse and fibrillar Aβ deposits, hyperphosphorylated/pathologically conformed Tau, and premature neuronal loss. Presence/absence of AD-like pathology was donor-specific (reproducible between individual organoids/iPSC lines/experiments). Pathology could be triggered in pathology-negative T21 organoids by CRISPR/Cas9-mediated elimination of the third copy of chromosome-21-gene BACE2, but prevented by combined chemical β and γ-secretase inhibition. We found that T21-organoids secrete increased proportions of Aβ-preventing (Aβ1-19) and Aβ-degradation products (Aβ1-20 and Aβ1-34). We show these profiles mirror in cerebrospinal fluid of people with DS. We demonstrate that this protective mechanism is mediated by BACE2-trisomy and cross-inhibited by clinically trialled BACE1-inhibitors. Combined, our data prove the physiological role of BACE2 as a dose-sensitive AD-suppressor gene, potentially explaining the dementia delay in ∼30% of people with DS. We also show that DS cerebral organoids could be explored as pre-morbid AD-risk population detector and a system for hypothesis-free drug screens as well as identification of natural suppressor genes for neurodegenerative diseases. url: https://doi.org/10.1101/2020.01.29.918037 doi: 10.1101/2020.01.29.918037 id: cord-102257-da4zn49x author: Almodaresi, Fatemeh title: Puffaligner: An Efficient and Accurate Aligner Based on the Pufferfish Index date: 2020-08-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Motivation Sequence alignment is one of the first steps in many modern genomic analyses, such as variant detection, transcript abundance estimation and metagenomic profiling. Unfortunately, it is often a computationally expensive procedure. As the quantity of data and wealth of different assays and applications continue to grow, the need for accurate and fast alignment tools persists. Results In this paper, we introduce PuffAligner, a fast, accurate and versatile aligner built on top of the Pufferfish index. PuffAligner is able to produce highly-sensitive alignments, similar to those of Bowtie2, but much more quickly. While exhibiting similar speed to the ultrafast STAR aligner, PuffAligner requires considerably less memory to construct its index and align reads. PuffAligner strikes a desirable balance with respect to the time, space, and accuracy tradeoffs made by different alignment tools, and provides a promising foundation on which to test new alignment ideas over large collections of sequences. Availability PuffAligner is a free and open-source software. It is implemented in C++14 and can be obtained from https://github.com/COMBINE-lab/pufferfish/tree/cigar-strings url: https://doi.org/10.1101/2020.08.11.246892 doi: 10.1101/2020.08.11.246892 id: cord-104031-vodwptdo author: Altshuler, Anna title: Capturing limbal epithelial stem cell population dynamics, signature, and their niche date: 2020-07-01 words: 10255.0 sentences: 580.0 pages: flesch: 53.0 cache: ./cache/cord-104031-vodwptdo.txt txt: ./txt/cord-104031-vodwptdo.txt summary: Tremendous efforts have been made by many research groups to discover markers for the identification of LSCs. Keratin 15 (Krt15) 33 41 , C/EBPdelta and BMI1 42 , ABCB5 43 , ABCG2 44 and P63 45 represent a partial list of genes proposed to identify LSCs. Recently, we have shown that the Krt15-GFP transgene (green fluorescent protein coding gene under the promoter of Krt15) labeled a discrete population of murine LSCs. Krt15-GFP + basal limbal epithelial cells were located at close proximity to the site of corneal regeneration origin, as evident by lineage tracing of Krt14 + cells 33 . In silico analysis revealed discrete cell states in the corneal epithelial lineage Cell filtering and unbiased clustering were performed with R package Seurat 46 revealing 11 cell populations displaying a markedly distinct signature of gene expression (Fig. 1b, S1b) . abstract: Stem cells (SCs) are traditionally viewed as rare, slow-cycling cells that follow deterministic rules dictating their self-renewal or differentiation. It was several decades ago, when limbal epithelial SCs (LSCs) that regenerate the corneal epithelium were one of the first sporadic, quiescent SCs ever discovered. However, LSC dynamics, heterogeneity and genetic signature are largely unknown. Moreover, recent accumulating evidence strongly suggested that epithelial SCs are actually abundant, frequently dividing cells that display stochastic behavior. In this work, we performed an in-depth analysis of the murine limbal epithelium by single-cell RNA sequencing and quantitative lineage tracing. The generated data provided an atlas of cell states of the corneal epithelial lineage, and particularly, revealed the co-existence of two novel LSC populations that reside in separate and well-defined sub-compartments. In the “outer” limbus, we identified a primitive widespread population of quiescent LSCs (qLSCs) that uniformly express Krt15/Gpha2/Ifitm3/Cd63 proteins, while the “inner” limbus host prevalent active LSCs (aLSCs) co-expressing Krt15-GFP/Atf3/Mt1-2/Socs3. Analysis of LSC population dynamics suggests that while qLSCs and aLSCs possess different proliferation rates, they both follow similar stochastic rules that dictate their self-renewal and differentiation. Finally, T cells were distributed in close proximity to qLSCs. Indeed, their absence or inhibition resulted in the loss of quiescence and delayed wound healing. Taken together, we propose that divergent regenerative strategies are tailored to properly support tissue-specific physiological constraints. The present study suggests that in the case of the cornea, quiescent epithelial SCs are abundant, follow stochastic rules and neutral drift dynamics. url: https://doi.org/10.1101/2020.06.30.179754 doi: 10.1101/2020.06.30.179754 id: cord-103990-qvuv289g author: Amster, Guy title: Changes in life history and population size can explain relative neutral diversity levels on X and autosomes in extant human populations date: 2019-09-09 words: 5518.0 sentences: 280.0 pages: flesch: 47.0 cache: ./cache/cord-103990-qvuv289g.txt txt: ./txt/cord-103990-qvuv289g.txt summary: We revisit this question in light of our new theory about the effects of life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly higher generation times in males than females, likely had multiple effects on human X-to-autosomes (X:A) polymorphism ratios, through the extent of male mutation bias, the equilibrium X:A ratios of effective population sizes, and differential responses to changes in population size. Our results suggest that ancestral human populations were highly polygynous; that non-African populations experienced a substantial reduction in polygyny and/or increase in male-biased generation times around the out of Africa bottleneck; and that extant diversity levels were affected by fairly recent changes in sex-specific life history. Indeed, we show that the ratios observed across human populations can be explained by demographic history, assuming plausible, sex-specific mutation rates, generation times and reproductive variances. abstract: In human populations, relative levels of neutral polymorphism on the X and autosomes differ markedly from each other and from the naive theoretical expectation of ¾. These differences have attracted considerable attention, with studies highlighting several potential causes, including male biased mutation and reproductive variance, historical changes in population size, and selection at linked loci. We revisit this question in light of our new theory about the effects of life history and given pedigree-based estimates of the dependence of human mutation rates on sex and age. We demonstrate that life history effects, particularly higher generation times in males than females, likely had multiple effects on human X-to-autosomes (X:A) polymorphism ratios, through the extent of male mutation bias, the equilibrium X:A ratios of effective population sizes, and differential responses to changes in population size. We also show that the standard approach of using divergence between species to correct for the male bias in mutation results in biased estimates of X:A effective population size ratios. We obtain alternative estimates using pedigree-based estimates of the male mutation bias, which reveal X:A ratios of effective population sizes to be considerably greater than previously appreciated. We then show that the joint effects of historical changes in life history and population size can explain X:A polymorphism ratios in extant human populations. Our results suggest that ancestral human populations were highly polygynous; that non-African populations experienced a substantial reduction in polygyny and/or increase in male-biased generation times around the out of Africa bottleneck; and that extant diversity levels were affected by fairly recent changes in sex-specific life history. Significance Statement All else being equal, the ratio of diversity levels on X and autosomes at selectively neutral sites should mirror the ratio of their numbers in the population and thus equal ¾. In reality, the ratios observed across human populations differ markedly from ¾ and from each other. Because from a population perspective, autosomes spend an equal number of generations in both sexes while the X spends twice as many generations in females, these departures from the naïve expectations likely reflect differences between male and female life histories and their effects on mutation processes. Indeed, we show that the ratios observed across human populations can be explained by demographic history, assuming plausible, sex-specific mutation rates, generation times and reproductive variances. url: https://doi.org/10.1101/763524 doi: 10.1101/763524 id: cord-348635-1pb2ag9j author: Anand, Praveen title: SARS-CoV-2 selectively mimics a cleavable peptide of human ENaC in a strategic hijack of host proteolytic machinery date: 2020-04-30 words: 1658.0 sentences: 94.0 pages: flesch: 51.0 cache: ./cache/cord-348635-1pb2ag9j.txt txt: ./txt/cord-348635-1pb2ag9j.txt summary: We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site (RRARSVAS), absent in any previous coronavirus sequenced, that results in mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). We extrapolate that the evolution of SARS-CoV-2 into a global coronavirus pandemic may be in part due to its targeted mimicry of human ENaC and hijack of the associated host proteolytic network. The overlap of the cell-types expressing ACE2 and ENaC-ɑ, and similar spatial distributions at the apical surfaces, suggest that SARS-CoV-2 may be leveraging the protease network responsible for ENaC cleavage. In order to extrapolate the tissue tropism of SARS-CoV-2 from the lens of the host proteolytic network, we assessed the co-expression of these proteases concomitant with the viral receptor ACE2 and ENaC-ɑ (Figure 2) . abstract: Molecular mimicry of host proteins is an evolutionary strategy adopted by viruses to evade immune surveillance and exploit host cell systems. We report that SARS-CoV-2 has evolved a unique S1/S2 cleavage site (RRARSVAS), absent in any previous coronavirus sequenced, that results in mimicry of an identical FURIN-cleavable peptide on the human epithelial sodium channel α-subunit (ENaC-α). Genetic truncation at this ENaC-α cleavage site causes aldosterone dysregulation in patients, highlighting the functional importance of the mimicked SARS-CoV-2 peptide. Single cell RNA-seq from 65 studies shows significant overlap between the expression of ENaC-α and ACE2, the putative receptor for the virus, in cell types linked to the cardiovascular-renal-pulmonary pathophysiology of COVID-19. Triangulating this cellular fingerprint with amino acid cleavage signatures of 178 human proteases shows the potential for tissue-specific proteolytic degeneracy wired into the SARS-CoV-2 lifecycle. We extrapolate that the evolution of SARS-CoV-2 into a global coronavirus pandemic may be in part due to its targeted mimicry of human ENaC and hijack of the associated host proteolytic network. url: https://doi.org/10.1101/2020.04.29.069476 doi: 10.1101/2020.04.29.069476 id: cord-259084-lwh3rww4 author: Anderson, Cole title: Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2 date: 2020-05-22 words: 1002.0 sentences: 66.0 pages: flesch: 52.0 cache: ./cache/cord-259084-lwh3rww4.txt txt: ./txt/cord-259084-lwh3rww4.txt summary: title: Pooling nasopharyngeal swab specimens to increase testing capacity for SARS-CoV-2 Current diagnosis of COVID-19 relies on the detection of SARS-CoV-2 RNA by RT-PCR in upper and lower respiratory specimens. Implementing a pooling strategy can significantly increase laboratory testing capacity while simultaneously reducing turnaround times for rapid identification and isolation of positive COVID-19 cases in high risk populations. This protocol allows for 35 the rapid detection of SARS-CoV-2 RNA from clinical specimens such as, nasopharyngeal and 36 oropharyngeal swabs, sputum, bronchoalveolar lavage, and tracheal aspirates. 43 In this study, we examined the feasibility of pooling nasopharyngeal swab specimens submitted 44 for COVID-19 testing using the CDC 2019-nCoV RT-PCR diagnostic panel without compromising 45 Specimens were submitted to 54 the Virology laboratory at Landstuhl Regional Medical Center for routine SARS-CoV-2 testing 55 using the CDC 2019-nCoV RT-PCR assay. Pooling nasopharyngeal/throat swab specimens to increase testing 176 capacity for influenza viruses by PCR abstract: The recent emergence of SARS-CoV-2 has lead to a global pandemic of unprecedented proportions. Current diagnosis of COVID-19 relies on the detection of SARS-CoV-2 RNA by RT-PCR in upper and lower respiratory specimens. While sensitive and specific, these RT-PCR assays require considerable supplies and reagents, which are often limited during global pandemics and surge testing. Here, we show that a nasopharyngeal swab pooling strategy can detect a single positive sample in pools of up to 10 samples without sacrificing RT-PCR sensitivity and specificity. We also report that this pooling strategy can be applied to rapid, moderate complexity assays, such as the BioFire COVID-19 test. Implementing a pooling strategy can significantly increase laboratory testing capacity while simultaneously reducing turnaround times for rapid identification and isolation of positive COVID-19 cases in high risk populations. url: https://doi.org/10.1101/2020.05.22.110932 doi: 10.1101/2020.05.22.110932 id: cord-321027-64y43o0y author: Andreano, Emanuele title: Identification of neutralizing human monoclonal antibodies from Italian Covid-19 convalescent patients date: 2020-05-09 words: 2287.0 sentences: 114.0 pages: flesch: 51.0 cache: ./cache/cord-321027-64y43o0y.txt txt: ./txt/cord-321027-64y43o0y.txt summary: The SARS-CoV-2 spike glycoprotein (S-protein) has a pivotal role in viral pathogenesis and it is 63 considered the main target to elicit potent neutralizing antibodies and the focus for the development 64 of therapeutic and prophylactic tools against this virus (3, 4) . Results shown in Table 1 and Figure 1 show that, among the seven donors 97 included in this study, six were able to produce high titers of SARS-CoV-2 S-protein specific 98 antibodies and in particular donors R-042, R-122 and R-188 showed the highest virus neutralizing 99 titers. In the case of SARS-CoV-2, where so far we do not have any effective therapeutic nor prophylactic 154 interventions, mAbs have the possibility to become one of the first drugs that can be used for 155 immediate therapy of any patient testing positive for the virus, and even to provide immediate 156 protection from infection in high risk populations. abstract: In the absence of approved drugs or vaccines, there is a pressing need to develop tools for therapy and prevention of Covid-19. Human monoclonal antibodies have very good probability of being safe and effective tools for therapy and prevention of SARS-CoV-2 infection and disease. Here we describe the screening of PBMCs from seven people who survived Covid-19 infection to isolate human monoclonal antibodies against SARS-CoV-2. Over 1,100 memory B cells were single-cell sorted using the stabilized prefusion form of the spike protein and incubated for two weeks to allow natural production of antibodies. Supernatants from each cell were tested by ELISA for spike protein binding, and positive antibodies were further tested for neutralization of spike binding to receptor(s) on Vero E6 cells and for virus neutralization in vitro. From the 1,167 memory B specific for SARS-CoV-2, we recovered 318 B lymphocytes expressing human monoclonals recognizing the spike protein and 74 of these were able to inhibit the binding of the spike protein to the receptor. Finally, 17 mAbs were able to neutralize the virus when assessed for neutralization in vitro. Lead candidates to progress into the drug development pipeline will be selected from the panel of neutralizing antibodies identified with the procedure described in this study. One Sentence Summary Neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for therapeutic and prophylactic interventions. url: https://doi.org/10.1101/2020.05.05.078154 doi: 10.1101/2020.05.05.078154 id: cord-321369-xzu2faol author: Andreano, Emanuele title: Extremely potent human monoclonal antibodies from convalescent Covid-19 patients date: 2020-10-07 words: 3685.0 sentences: 192.0 pages: flesch: 52.0 cache: ./cache/cord-321369-xzu2faol.txt txt: ./txt/cord-321369-xzu2faol.txt summary: By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2. As for the authentic virus neutralization assay, supernatants containing naturally produced IgG or IgA were tested for their ability to protect the layer of Vero E6 cells from the cytopathic effect triggered by SARS-CoV-2 infection (Fig. S2) . This work describes a systematic screening of memory B cells from convalescent people to identify extremely potent human monoclonal antibodies against the spike protein of the SARS-CoV-2 virus, to be used for prevention and therapy of Covid-19. abstract: Human monoclonal antibodies are safe, preventive and therapeutic tools, that can be rapidly developed to help restore the massive health and economic disruption caused by the Covid-19 pandemic. By single cell sorting 4277 SARS-CoV-2 spike protein specific memory B cells from 14 Covid-19 survivors, 453 neutralizing antibodies were identified and 220 of them were expressed as IgG. Up to 65,9% of monoclonals neutralized the wild type virus at a concentration of >500 ng/mL, 23,6% neutralized the virus in the range of 100 - 500 ng/mL and 9,1% had a neutralization potency in the range of 10 - 100 ng/mL. Only 1,4% neutralized the authentic virus with a potency of 1-10 ng/mL. We found that the most potent neutralizing antibodies are extremely rare and recognize the RBD, followed in potency by antibodies that recognize the S1 domain, the S-protein trimeric structure and the S2 subunit. The three most potent monoclonal antibodies identified were able to neutralize the wild type and D614G mutant viruses with less than 10 ng/mL and are good candidates for the development of prophylactic and therapeutic tools against SARS-CoV-2. One Sentence Summary Extremely potent neutralizing human monoclonal antibodies isolated from Covid-19 convalescent patients for prophylactic and therapeutic interventions. url: https://doi.org/10.1101/2020.10.07.328302 doi: 10.1101/2020.10.07.328302 id: cord-261662-d0tg9i90 author: Andres, Cristina title: Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients date: 2020-06-08 words: 4673.0 sentences: 214.0 pages: flesch: 52.0 cache: ./cache/cord-261662-d0tg9i90.txt txt: ./txt/cord-261662-d0tg9i90.txt summary: title: Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. Because of the importance of the S protein, we carried out a deep-sequencing study of the S gene in upper respiratory tract samples from 18 patients with mild or severe SARS-CoV-2 disease. The fact that the truncated S protein was present in only a low percentage of the entire viral quasispecies suggests that natural selection may have designed a favorable equilibrium in which a limited number of deleted virions are generated to balance virus production with infection of new cells during disease progression. abstract: The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We propose that natural selection has favored a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability. url: https://doi.org/10.1101/2020.06.03.129585 doi: 10.1101/2020.06.03.129585 id: cord-102555-vnmc9ii8 author: Araki, Takuma title: Sphingobium sp. SYK-6 syringate O-demethylase gene is regulated by DesX, unlike other vanillate and syringate catabolic genes regulated by DesR date: 2020-07-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Syringate and vanillate are the major metabolites of lignin biodegradation. In Sphingobium sp. strain SYK-6, syringate is O demethylated to gallate by consecutive reactions catalyzed by DesA and LigM, and vanillate is O demethylated to protocatechuate by a reaction catalyzed by LigM. The gallate ring is cleaved by DesB, and protocatechuate is catabolized via the protocatechuate 4,5-cleavage pathway. The transcriptions of desA, ligM, and desB are induced by syringate and vanillate, while that of ligM and desB are negatively regulated by the MarR-type transcriptional regulator DesR, which is not involved in desA regulation. Here we clarified the regulatory system for desA transcription by analyzing the IclR-type transcriptional regulator desX, located downstream of desA. Quantitative reverse transcription (RT)-PCR analyses of a desX mutant indicates that the transcription of desA was negatively regulated by DesX. In contrast, DesX was not involved in the regulation of ligM and desB. The ferulate catabolic genes (ferBA) under the control of a MarR-type transcriptional regulator FerC are located upstream of desA. RT-PCR analyses suggest that the ferB-ferA-SLG_25010-desA gene cluster consists of the ferBA operon and the SLG_25010-desA operon. Promoter assays reveal that a syringate- and vanillate-inducible promoter is located upstream of SLG_25010. Purified DesX bound to this promoter region, which overlaps with an 18-bp-inverted repeat sequence that appears to be essential for the DNA binding of DesX. Syringate and vanillate inhibited the DNA binding of DesX, indicating that these compounds are effector molecules of DesX. IMPORTANCE Syringate is a major degradation product in the microbial and chemical degradation of syringyl lignin. Along with other low-molecular-weight aromatic compounds, syringate is produced by chemical lignin depolymerization. Converting this mixture into value-added chemicals using bacterial metabolism (i.e., biological funneling) is a promising option for lignin valorization. To construct an efficient microbial lignin conversion system, it is necessary to identify and characterize the genes involved in the uptake and catabolism of lignin-derived aromatic compounds and elucidate their transcriptional regulation. In this study, we found that the transcription of desA, encoding syringate O-demethylase in SYK-6, is regulated by an IclR-type of transcriptional regulator, DesX. The findings of this study, combined with our previous results on desR (a MarR transcriptional regulator that controls the transcription of ligM and desB), provide an overall picture of the transcriptional regulatory systems for syringate and vanillate catabolism in SYK-6. url: https://doi.org/10.1101/2020.07.27.224295 doi: 10.1101/2020.07.27.224295 id: cord-356264-q0yqnlyl author: Armijos-Jaramillo, Vinicio title: SARS-CoV-2, an evolutionary perspective of interaction with human ACE2 reveals undiscovered amino acids necessary for complex stability date: 2020-03-23 words: 4974.0 sentences: 253.0 pages: flesch: 53.0 cache: ./cache/cord-356264-q0yqnlyl.txt txt: ./txt/cord-356264-q0yqnlyl.txt summary: With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor hACE2. We employ a multidisciplinary approach to look for evidence of diversifying selection on the S-protein gene, and model the interactions between human ACE2 (hACE2) and the RBD of selected coronavirus strains, which ultimately afforded us novel insights detailing virus and host cell interactions. All these experiments were performed again using the S-protein genes of a shorter list of accessions and more distantly related (broad dataset) to SARS-COV-2 (AY304488, AY395003, DQ412043, FJ882957, KY417144, MG772933, MG772934, MN908947, NC_004718) to test the reproducibility of the predicted branches and sites under positive selection. Modeling results suggest that interference with the hot spot 353 could be and effective strategy for inhibiting the recognition of the RBD of the SARS-COV-2 spike protein by its human host receptor ACE2 and hence prevent infections. abstract: The emergence of SARS-CoV-2 has resulted in more than 200,000 infections and nearly 9,000 deaths globally so far. This novel virus is thought to have originated from an animal reservoir, and acquired the ability to infect human cells using the SARS-CoV cell receptor hACE2. In the wake of a global pandemic it is essential to improve our understanding of the evolutionary dynamics surrounding the origin and spread of a novel infectious disease. One way theory predicts selection pressures should shape viral evolution is to enhance binding with host cells. We first assessed evolutionary dynamics in select betacoronavirus spike protein genes to predict where these genomic regions are under directional or purifying selection between divergent viral lineages at various scales of relatedness. With this analysis, we determine a region inside the receptor-binding domain with putative sites under positive selection interspersed among highly conserved sites, which are implicated in structural stability of the viral spike protein and its union with human receptor hACE2. Next, to gain further insights into factors associated with coronaviruses recognition of the human host receptor, we performed modeling studies of five different coronaviruses and their potential binding to hACE2. Modeling results indicate that interfering with the salt bridges at hot spot 353 could be an effective strategy for inhibiting binding, and hence for the prevention of coronavirus infections. We also propose that a glycine residue at the receptor binding domain of the spike glycoprotein can have a critical role in permitting bat variants of the coronaviruses to infect human cells. url: https://doi.org/10.1101/2020.03.21.001933 doi: 10.1101/2020.03.21.001933 id: cord-103580-6rf1xs0d author: Arokiaraj, Mark Christopher title: A Novel Method of Immunomodulation of Endothelial cells Using Streptococcus Pyogenes and its Lysate date: 2020-05-15 words: 3669.0 sentences: 253.0 pages: flesch: 44.0 cache: ./cache/cord-103580-6rf1xs0d.txt txt: ./txt/cord-103580-6rf1xs0d.txt summary: In this study, a novel method of immune-modulation to modify the endothelial function was studied to modulate the features of the endothelial cells, and thereby to reduce coronary artery disease and other disorders modulated by endothelium. Conclusion There is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using streptococcus pyogenes and its lysates. The study was performed in search of novel applications of streptococcus pyogenes in regulating immune functions, and its related effects on cardiovascular and its pleiotropic functions. When the cells were treated with streptococcus pyogenes'' lysate, the levels of BLC -the B lymphocyte chemoattractant protein (CXCL13) was increased. 72 The heat map analysis shows a significant change in more proteins, and thereby it is possible to infer that streptococcus has a role in immune regulation. 78 Our study also reflects the immune regulation changes due to streptococcus pyogenes as well as by its lysate. abstract: Background Coronary artery diseases and autoimmune disorders are common in clinical practice. In this study, a novel method of immune-modulation to modify the endothelial function was studied to modulate the features of the endothelial cells, and thereby to reduce coronary artery disease and other disorders modulated by endothelium. Methods HUVEC cells were seeded in the cell culture, and streptococcus pyogenes were added to the cell culture, and the supernatant was studied for the secreted proteins. In the second phase, the bacterial lysate was synthesized, and the lysate was added to cell culture; and the proteins in the supernatant were studied at various time intervals. Results When streptococcus pyogenes alone was added to culture, E Cadherin, Angiostatin, EpCAM and PDGF-AB were some of the biomarkers elevated significantly. HCC1, IGFBP2 and TIMP were some of the biomarkers which showed a reduction. When the lysate was added, the cell-culture was maintained for a longer time, and it showed the synthesis of immune regulatory cytokines. Heatmap analysis showed a significant number of proteins/cytokines concerning the immune/pathways, and toll-like receptors superfamily were modified. BLC, IL 17, BMP 7, PARC, Contactin2, IL 10 Rb, NAP 2 (CXCL 7), Eotaxin 2 were maximally increased. By principal component analysis, the results observed were significant. Conclusion There is potential for a novel method of immunomodulation of the endothelial cells, which have pleiotropic functions, using streptococcus pyogenes and its lysates. url: https://doi.org/10.1101/2020.05.13.082180 doi: 10.1101/2020.05.13.082180 id: cord-328636-1q71gjwt author: Arora, Kajal title: Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate date: 2020-05-19 words: 2249.0 sentences: 118.0 pages: flesch: 55.0 cache: ./cache/cord-328636-1q71gjwt.txt txt: ./txt/cord-328636-1q71gjwt.txt summary: title: Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). In this study, we report the first successful self-assembly of the SARS CoV-2 VLP by co-expression of the S, E and M proteins in Saccharomyces cerevisiae expression platform. cerevisiae, recombinant construct for the expression of S and E protein, pYRE100_CSP_CEP_His and M protein, pYRI100_CMP_His construct were cotransformed into the host and the positive clones were selected on YNB-URA-LEU plates. Episomal constructs of S, E and M with His tag, pYRE100_CSP_His, pYRE100_CMP_His and pYRE100_CEP_His plasmid and host vector pYRE100 plasmid were transformed into proprietary protease deficient PYPD yeast expression strain using Lithium acetate/SS-DNA/PEG mediated protocol and transformants were selected over selective YNB Glucose minus URA plates. abstract: Spike, Envelope and Membrane proteins from the SARS CoV-2 virus surface coat are important vaccine targets. We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). This design as a multi-antigenic VLP for SARS CoV-2 has the potential to be a scalable vaccine candidate. The VLP is confirmed by transmission electron microscopy (TEM) images of the SARS CoV-2, along with supportive HPLC, Dynamic Light Scattering (DLS) and allied analytical data. The images clearly outline the presence of a “Corona” like morphology, and uniform size distribution. url: https://doi.org/10.1101/2020.05.18.099234 doi: 10.1101/2020.05.18.099234 id: cord-104133-d01joq23 author: Arthur, Ronan F. title: Adaptive social contact rates induce complex dynamics during epidemics date: 2020-07-14 words: 5240.0 sentences: 300.0 pages: flesch: 55.0 cache: ./cache/cord-104133-d01joq23.txt txt: ./txt/cord-104133-d01joq23.txt summary: We develop a model for adaptive optimal control of the effective social contact rate within a Susceptible-Infectious-Susceptible (SIS) epidemic model using a dynamic utility function with delayed information. To represent endogenous behavior-change, we start with the classical discrete-time 112 susceptible-infected-susceptible (SIS) model [28] , which, when incidence is relatively 113 small compared to the total population [29, 30] , can be written in terms of the recursions 114 In order to introduce human behavior, we 121 substitute for b a time-dependent b t , which is a function of both b 0 , the probability that 122 disease transmission takes place on contact, and a dynamic social rate of contact c t 123 whose optimal value, c * t , is determined at each time t as in economic epidemiological 124 models [31] , namely abstract: The COVID-19 pandemic has posed a significant dilemma for governments across the globe. The public health consequences of inaction are catastrophic; but the economic consequences of drastic action are likewise catastrophic. Governments must therefore strike a balance in the face of these trade-offs. But with critical uncertainty about how to find such a balance, they are forced to experiment with their interventions and await the results of their experimentation. Models have proved inaccurate because behavioral response patterns are either not factored in or are hard to predict. One crucial behavioral response in a pandemic is adaptive social contact: potentially infectious contact between people is deliberately reduced either individually or by fiat; and this must be balanced against the economic cost of having fewer people in contact and therefore active in the labor force. We develop a model for adaptive optimal control of the effective social contact rate within a Susceptible-Infectious-Susceptible (SIS) epidemic model using a dynamic utility function with delayed information. This utility function trades off the population-wide contact rate with the expected cost and risk of increasing infections. Our analytical and computational analysis of this simple discrete-time deterministic model reveals the existence of a non-zero equilibrium, oscillatory dynamics around this equilibrium under some parametric conditions, and complex dynamic regimes that shift under small parameter perturbations. These results support the supposition that infectious disease dynamics under adaptive behavior-change may have an indifference point, may produce oscillatory dynamics without other forcing, and constitute complex adaptive systems with associated dynamics. Implications for COVID-19 include an expectation of fluctuations, for a considerable time, around a quasi-equilibrium that balances public health and economic priorities, that shows multiple peaks and surges in some scenarios, and that implies a high degree of uncertainty in mathematical projections. Author summary Epidemic response in the form of social contact reduction, such as has been utilized during the ongoing COVID-19 pandemic, presents inherent tradeoffs between the economic costs of reducing social contacts and the public health costs of neglecting to do so. Such tradeoffs introduce an interactive, iterative mechanism which adds complexity to an infectious disease system. Consequently, infectious disease modeling typically has not included dynamic behavior change that must address such a tradeoff. Here, we develop a theoretical model that introduces lost or gained economic and public health utility through the adjustment of social contact rates with delayed information. We find this model produces an equilibrium, a point of indifference where the tradeoff is neutral, and at which a disease will be endemic for a long period of time. Under small perturbations, this model exhibits complex dynamic regimes, including oscillatory behavior, runaway exponential growth, and eradication. These dynamics suggest that for epidemic response that relies on social contact reduction, secondary waves and surges with accompanied business re-closures and shutdowns may be expected, and that accurate projection under such circumstances is unlikely. url: https://doi.org/10.1101/2020.04.14.028407 doi: 10.1101/2020.04.14.028407 id: cord-283109-ka3n9pft author: Arumugam, Arunkumar title: The Potential Use of Unprocessed Sample for RT-qPCR Detection of COVID-19 without an RNA Extraction Step date: 2020-04-08 words: 1725.0 sentences: 103.0 pages: flesch: 58.0 cache: ./cache/cord-283109-ka3n9pft.txt txt: ./txt/cord-283109-ka3n9pft.txt summary: Using flu and RSV clinical specimens, we have collected evidence that the RT-qPCR assay can be performed directly on patient sample material from a nasal swab immersed in virus transport medium (VTM) without an RNA extraction step. Using Inf and RSV clinical specimens, we successfully performed RT-qPCR reactions by simply adding a few microliters of the unprocessed sample in viral transport medium (VTM) directly into the RT-qPCR assay master mix. We next tested whether the RNA from SARS-CoV-2 can be detected by directly spiking samples of the non-replicative recombinant virus particles (SeraCare AccuPlex SARS-CoV-2 reference material) in VTM to master mix without an extraction step. As shown in Fig. 3 , the SARS-CoV-2 RNA from directly spiked samples was successfully detected by the RT-qPCR reaction without a nucleic acid extraction step (N1 target shown). abstract: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection.1–4 It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. With many PCR-based molecular assays, an extraction step is routinely used as part of the protocol. This step can take up a significant amount of time and labor, especially if the extraction is performed manually. Long assay time, partly caused by slow sample preparation steps, has created a large backlog when testing patient samples suspected of COVID-19. Using flu and RSV clinical specimens, we have collected evidence that the RT-qPCR assay can be performed directly on patient sample material from a nasal swab immersed in virus transport medium (VTM) without an RNA extraction step. We have also used this approach to test for the direct detection of SARS-CoV-2 reference materials spiked in VTM. Our data, while preliminary, suggest that using a few microliters of these untreated samples still can lead to sensitive test results. If RNA extraction steps can be omitted without significantly affecting clinical sensitivity, the turn-around time of COVID-19 tests and the backlog we currently experience can be reduced drastically. Next, we will confirm our findings using patient samples. url: https://doi.org/10.1101/2020.04.06.028811 doi: 10.1101/2020.04.06.028811 id: cord-354725-lqio7l8k author: Arumugam, Arunkumar title: A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings date: 2020-04-30 words: 3478.0 sentences: 203.0 pages: flesch: 64.0 cache: ./cache/cord-354725-lqio7l8k.txt txt: ./txt/cord-354725-lqio7l8k.txt summary: Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. 5 Despite its established performance in sensitivity and specificity, RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many resource limiting settings. Two water baths (one for denaturation and one for the reverse transcription and then the annealing/extension steps) were made using food storage plastic containers heated by sous vide immersion heaters. We tested this rapid water bath RT-PCR approach using untreated or heat-inactivated samples directly added to one-step RT-PCR master mixes without an RNA extraction step. Extracted templates from COVID-19 positive clinical specimens and contrived negative samples were tested using water bath-based RT-PCR. With a 3-minute RNA extraction protocol, we were able to get positive RT-PCR results with all ten COVID-19 positive clinical samples. abstract: Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection. It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many low resource settings and developing countries. As a pandemic, COVID-19 has quickly spread to the rest of the world. Many underdeveloped and developing counties do not have the means for fast and accurate COVID-19 detection to control this outbreak. Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. Rapid RT-PCR was achieved using thin-walled PCR tubes and a setup including sous vide immersion heaters/circulators. Our data suggest that rapid RT-PCR can be implemented for sensitive and specific molecular diagnosis of COVID-19 in situations where sophisticated laboratory instruments are not available. url: https://doi.org/10.1101/2020.04.29.069591 doi: 10.1101/2020.04.29.069591 id: cord-353742-k4gxww2c author: Arévalo, AP title: Ivermectin reduces coronavirus infection in vivo: a mouse experimental model date: 2020-11-02 words: 721.0 sentences: 66.0 pages: flesch: 48.0 cache: ./cache/cord-353742-k4gxww2c.txt txt: ./txt/cord-353742-k4gxww2c.txt summary: SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases. abstract: SARS-CoV2 is a single strand RNA virus member of the type 2 coronavirus family, responsible for causing COVID-19 disease in humans. The objective of this study was to test the ivermectin drug in a murine model of coronavirus infection using a type 2 family RNA coronavirus similar to SARS-CoV2, the mouse hepatitis virus (MHV). BALB/cJ female mice were infected with 6,000 PFU of MHV-A59 (Group Infected; n=20) and immediately treated with one single dose of 500 μg/kg of ivermectin (Group Infected + IVM; n=20), or were not infected and treated with PBS (Control group; n=16). Five days after infection/treatment, mice were euthanized to obtain different tissues to check general health status and infection levels. Overall results demonstrated that viral infection induces the typical MHV disease in infected animals, with livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while ivermectin administration showed a better health status with lower viral load (23,192 AU; p<0.05) and few livers with histopathological damage (p<0.05), not showing statistical differences with control mice (P=NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in treated mice compared to infected animals. In conclusion, ivermectin seems to be effective to diminish MHV viral load and disease in mice, being a useful model for further understanding new therapies against coronavirus diseases. url: https://doi.org/10.1101/2020.11.02.363242 doi: 10.1101/2020.11.02.363242 id: cord-268034-7id7sfsu author: Auerswald, Heidi title: Assessment of Inactivation Procedures for SARS-CoV-2 date: 2020-05-28 words: 1620.0 sentences: 100.0 pages: flesch: 47.0 cache: ./cache/cord-268034-7id7sfsu.txt txt: ./txt/cord-268034-7id7sfsu.txt summary: This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. The buffers used in this lysis step yield varying results [11, 13, 15, 16] ; however, unlike 224 previous studies [11] , this study found that AVL buffer alone was successfully able to fully 225 inactivate up to 5 log10 of virus from three different primary isolates of SARS-CoV-2. Previous 234 studies have shown that GITC-lysis buffers are able to inactivate SARS-CoV-2 samples [11, 12] ; 235 however, the addition of Triton-X may be necessary for complete inactivation [11] . Therefore, formaldehyde treatment does not appear to be a 247 solution for increased molecular SARS-CoV-2 testing; however, it does remain a viable alternative 248 for sample inactivation or disinfection. abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of Coronavirus disease 2019 (COVID-19), presents a challenge to laboratorians and healthcare workers around the world. Handling of biological samples from individuals infected with the SARS-CoV-2 virus requires strict biosafety and biosecurity measures. Within the laboratory, non-propagative work with samples containing the virus requires, at minimum, Biosafety Level-2 (BSL-2) techniques and facilities. Therefore, handling of SARS-CoV-2 samples remains a major concern in areas and conditions where biosafety and biosecurity for specimen handling is difficult to maintain, such as in rural laboratories or austere field testing sites. Inactivation through physical or chemical means can reduce the risk of handling live virus and increase testing ability worldwide. Herein we assess several chemical and physical inactivation techniques employed against SARS-CoV-2 isolates from Cambodian COVID-19 patients. This data demonstrates that all chemical (AVL, inactivating sample buffer and formaldehyde) and heat treatment (56°C and 98°C) methods tested completely inactivated viral loads of up to 5 log10. url: https://doi.org/10.1101/2020.05.28.120444 doi: 10.1101/2020.05.28.120444 id: cord-102270-rfhtlodc author: Azhar, Mohd. title: Rapid, field-deployable nucleobase detection and identification using FnCas9 date: 2020-04-21 words: 3971.0 sentences: 217.0 pages: flesch: 50.0 cache: ./cache/cord-102270-rfhtlodc.txt txt: ./txt/cord-102270-rfhtlodc.txt summary: We then fixed the position of this mutation with respect to PAM and changed every other base in the sgRNA sequence to identify which combination led to complete loss of cleavage of a wild type substrate in an in vitro cleavage (IVC) assay with FnCas9 ( Figure 1B, Supplementary Figure 1A ). Taken together, these experiments suggest that FELUDA design can be universally used for detection of SNVs and and would not require extensive optimization or validation steps for new SNVs. To aid users for quick design and implementation of FELUDA for a target SNV, we have developed a webtool JATAYU (Junction for Analysis and Target Design for Your FELUDA assay) that incorporates the above features and generates primer sequences for amplicon and sgRNA synthesis (https:// jatayu.igib.res.in, Supplementary Figure 2 ). abstract: Detection of pathogenic sequences or variants in DNA and RNA through a point-of-care diagnostic approach is valuable for rapid clinical prognosis. In recent times, CRISPR based detection of nucleic acids has provided an economical and quicker alternative to sequencing-based platforms which are often difficult to implement in the field. Here, we present FnCas9 Editor Linked Uniform Detection Assay (FELUDA) that employs a highly accurate enzymatic readout for detecting nucleotide sequences, identifying nucleobase identity and inferring zygosity with precision. We demonstrate that FELUDA output can be adapted to multiple signal detection platforms and can be quickly designed and deployed for versatile applications including rapid diagnosis during infectious disease outbreaks like COVID-19. url: https://doi.org/10.1101/2020.04.07.028167 doi: 10.1101/2020.04.07.028167 id: cord-104142-0nfprn2a author: Azmi, Maryam A. title: A laboratory module that explores RNA interference and codon optimization through fluorescence microscopy using Caenorhabditis elegans date: 2020-10-19 words: 5438.0 sentences: 276.0 pages: flesch: 50.0 cache: ./cache/cord-104142-0nfprn2a.txt txt: ./txt/cord-104142-0nfprn2a.txt summary: In this laboratory module, students learn about RNA interference (RNAi) and codon optimization using the research organism Caenorhabditis elegans (C. elegans Understand the process of RNA interference and importance of codon optimization Learn basic microscopy techniques and image analysis Learn how to properly use the scientific method Enhance critical thinking skills Learning Objectives Students will be able to: Lab 1 and 2: Identify specific larval stages of C. elegans larvae using alkaline hypochlorite treatment Understand codon usage Formulate hypotheses and design a controlled experiment Lab 3 and 4: Acquire images using an epifluorescence microscope Effectively communicate results and formulate conclusions from data Describe what RNAi is and how it affects gene expression/activity Calculate mean fluorescent intensity from acquired fluorescence micrographs Perform statistical tests to determine the significance of results Generate publication quality figures and figure legends abstract: Authentic research experiences are beneficial to students allowing them to gain laboratory and problem-solving skills as well as foundational research skills in a team-based setting. We designed a laboratory module to provide an authentic research experience to stimulate curiosity, introduce students to experimental techniques, and promote higher-order thinking. In this laboratory module, students learn about RNA interference (RNAi) and codon optimization using the research organism Caenorhabditis elegans (C. elegans). Students are given the opportunity to perform a commonly used method of gene downregulation in C. elegans where they visualize gene depletion using fluorescence microscopy and quantify the efficacy of depletion using quantitative image analysis. The module presented here educates students on how to report their results and findings by generating publication quality figures and figure legends. The activities outlined exemplify ways by which students can acquire the critical thinking, data interpretation, and technical skills, which are beneficial for future laboratory classes, independent inquiry-based research projects and careers in the life sciences and beyond. SCIENTIFIC TEACHING CONTENT Learning Goals Gain experience working with C. elegans Understand the process of RNA interference and importance of codon optimization Learn basic microscopy techniques and image analysis Learn how to properly use the scientific method Enhance critical thinking skills Learning Objectives Students will be able to: Lab 1 and 2: Identify specific larval stages of C. elegans Synchronize C. elegans larvae using alkaline hypochlorite treatment Understand codon usage Formulate hypotheses and design a controlled experiment Lab 3 and 4: Acquire images using an epifluorescence microscope Effectively communicate results and formulate conclusions from data Describe what RNAi is and how it affects gene expression/activity Calculate mean fluorescent intensity from acquired fluorescence micrographs Perform statistical tests to determine the significance of results Generate publication quality figures and figure legends url: https://doi.org/10.1101/2020.10.17.344069 doi: 10.1101/2020.10.17.344069 id: cord-103592-lkngp2u6 author: Bachmaier, Kurt title: Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date: 2020-07-02 words: 6316.0 sentences: 336.0 pages: flesch: 47.0 cache: ./cache/cord-103592-lkngp2u6.txt txt: ./txt/cord-103592-lkngp2u6.txt summary: Using cecal ligation and puncture (CLP), a reproducible and clinically relevant mouse model of polymicrobial infection that causes ALI, we found that in naïve control mice after 2 sequential i.v. injections of ANP only ~4% of lung PMN endocytosed ANP as evidenced by ANP-specific fluorescence ( Figure 1B) . Importantly, we found that CCR1 receptor cell surface expression, consistent with the mRNA data, was significantly greater on lung ANP high PMN than in ANP low PMN before and 3h, 6h, and 12h after LPS stimulation ( Figure 3B ). We observed that nitrotyrosine-specific staining in inflammatory and parenchymal cells was significantly reduced in lungs and livers of mice treated with PANP when compared to ANP-treated controls ( Figure 6D ,E). Measuring a markers of overall cell damage, lactic dehydrogenase (LDH) (34) , revealed that the polymicrobial sepsis-induced increased serum activity of LDH was significantly reduced by PANP treatment when compared to ANP treated controls ( Figure 6G ). abstract: Inflammatory tissue injury such as acute lung injury (ALI) is a disorder that leads to respiratory failure, a major cause of morbidity and mortality worldwide. Excessive neutrophil influx is a critical pathogenic factor in the development of ALI. Here, we identify the subset of neutrophils that is responsible for ALI and lethality in polymicrobial sepsis. The pro-inflammatory neutrophil subpopulation was characterized by its unique ability to endocytose albumin nanoparticles (ANP), upregulation of pro-inflammatory cytokines and chemokines as well as the excessive production of reactive oxygen species (ROS) in models of endotoxemia and septicemia. ANP delivery of the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, to the susceptible subset of neutrophils, prevented ALI and mortality in mice subjected to polymicrobial infection. Targeted inhibition of Syk in ANP-susceptible neutrophils had no detrimental effect on neutrophil-dependent host defense because the subset of ANPlow neutrophils effectively controlled polymicrobial infection. The results show that neutrophil heterogeneity can be leveraged therapeutically to prevent ALI without compromising host defense. url: https://doi.org/10.1101/2020.06.30.180927 doi: 10.1101/2020.06.30.180927 id: cord-309512-d8n9711b author: Bacus, Michael G. title: Global genetic patterns reveal host tropism versus cross-taxon transmission of bat Betacoronaviruses date: 2020-05-05 words: 1025.0 sentences: 71.0 pages: flesch: 50.0 cache: ./cache/cord-309512-d8n9711b.txt txt: ./txt/cord-309512-d8n9711b.txt summary: Emerging infectious diseases due to coronavirus (CoV) infections have received significant global attention in the past decade and have been linked to bats as the original source. As such, deviant patterns were observed such as for 2D-IV, wherein cross-taxon transmission due to overlap in bat habitats and geographic range among genetically divergent African bat hosts could have played a strong role on their shared CoV lineages. In fact, a few bat taxa especially the subfamily Pteropodinae were shown to host diverse groups of BetaCoVs. Therefore, ecological imbalances that disturb bat distribution may lead to loss of host specificity through cross-taxon transmission and multi-CoV infection. Importance Bat Betacoronaviruses (BetaCoVs) pose a significant threat to global public health and have been implicated in several epidemics such as the recent pandemic by severe acute respiratory syndrome coronavirus 2. Although bat BetaCoVs are host taxon-specific, their evolutionary pathways are different from evolution with its host. abstract: Emerging infectious diseases due to coronavirus (CoV) infections have received significant global attention in the past decade and have been linked to bats as the original source. The diversity, distribution, and host associations of bat CoVs were investigated to assess their potential for zoonotic transmission. Phylogenetic, network, and principal coordinate analysis confirmed the classification of betacoronaviruses (BetaCoVs) into five groups (2A to 2E) and a potentially novel group, with further division of 2D into five subgroups. The genetic co-clustering of BetaCoVs among closely related bats reflects host taxon-specificity with each bat family as the host for a specific BetaCoV group, potentially a natural barrier against random transmission. The divergent pathway of BetaCoV and host evolution suggests that the viruses were introduced just prior to bat dispersal and speciation. As such, deviant patterns were observed such as for 2D-IV, wherein cross-taxon transmission due to overlap in bat habitats and geographic range among genetically divergent African bat hosts could have played a strong role on their shared CoV lineages. In fact, a few bat taxa especially the subfamily Pteropodinae were shown to host diverse groups of BetaCoVs. Therefore, ecological imbalances that disturb bat distribution may lead to loss of host specificity through cross-taxon transmission and multi-CoV infection. Hence, initiatives that minimize the destruction of wildlife habitats and limit wildlife-livestock-human interfaces are encouraged to help maintain the natural state of bat BetaCoVs in the wild. Importance Bat Betacoronaviruses (BetaCoVs) pose a significant threat to global public health and have been implicated in several epidemics such as the recent pandemic by severe acute respiratory syndrome coronavirus 2. Here, we show that bat BetaCoVs are predominantly host-specific, which could be a natural barrier against infection of other host types. However, a strong overlap in bat habitat and geographic range may facilitate viral transmission to unrelated hosts, and a few bat families have already been shown to host multi-CoV variants. We predict that continued disturbances on the ecological balance may eventually lead to loss of host specificity. When combined with enhanced wildlife-livestock-human interfaces, spillover to humans may be further facilitated. We should therefore start to define the ecological mechanisms surrounding zoonotic events. Global surveillance should be expanded and strengthened to assess the complete picture of bat coronavirus diversity and distribution and their potential to cause spillover infections. url: https://doi.org/10.1101/2020.05.04.076281 doi: 10.1101/2020.05.04.076281 id: cord-300423-q2i328sz author: Bai, Lei title: Co-infection of influenza A virus enhances SARS-CoV-2 infectivity date: 2020-10-14 words: 1470.0 sentences: 106.0 pages: flesch: 64.0 cache: ./cache/cord-300423-q2i328sz.txt txt: ./txt/cord-300423-q2i328sz.txt summary: Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. The results demonstrate that the pre-infection of 57 IAV strongly enhances the infectivity of SARS-CoV-2 by boosting viral entry in the cells 58 and by elevating viral load plus more severe lung damage in infected mice. We 75 further tested more cell lines to show that the enhancement of the pSARS-CoV-2 infectivity 76 by IAV was a general effect although the increased folds were different (lower basal level 77 of infectivity, higher enhancement fold) (Fig.1D ). We found that the pre-infection of IAV 80 strongly increased the copy numbers of the SARS-CoV-2 genome (E and N genes) in both 81 cell lysates and supernatants of A549 (~15 folds) (Fig.1F) . The histological data in Fig. 2D further illustrated that IAV and 98 SARS-CoV-2 co-infection induced more severe lung pathologic changes with massive 99 infiltrating cells and obvious alveolar necrosis as compared to SARS-CoV-2 single 100 infection or mock infection. abstract: The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic. url: https://doi.org/10.1101/2020.10.14.335893 doi: 10.1101/2020.10.14.335893 id: cord-270550-if748w2n author: Bailey, Adam L. title: SARS-CoV-2 Infects Human Engineered Heart Tissues and Models COVID-19 Myocarditis date: 2020-11-05 words: 5808.0 sentences: 440.0 pages: flesch: 49.0 cache: ./cache/cord-270550-if748w2n.txt txt: ./txt/cord-270550-if748w2n.txt summary: To ascertain whether human pluripotent stem cell-derived cardiomyocytes (hPSC-derived 150 CMs) can serve as an appropriate model to study cardiac SARS-CoV-2 infection, we measured 151 ACE2 mRNA expression in hPSC-derived CMs. Quantitative RT-PCR revealed that hPSC-152 derived CMs abundantly expressed ACE2 mRNA. We identified numerous host genes that were differentially 226 regulated upon SARS-CoV-2 infection in each of the examined cell types and two-dimensional 227 tissues (Fig. 3c) . 236 GO pathway analysis revealed that infected hPSC-derived CMs and two-dimensional co-237 culture tissues showed upregulation of genes associated with immune cell activation, stress-238 induced transcription, and responses to pathogens including viruses. Consistent with the 343 possibility that disrupted sarcomere gene expression might contribute to reduced EHT 344 contractility, immunostaining of hPSC-derived CMs infected with SARS-CoV-2 revealed evidence 345 of sarcomere loss 3 days following infection (Fig. 6c) , a time point that preceded cell death. abstract: Epidemiological studies of the COVID-19 pandemic have revealed evidence of cardiac involvement and documented that myocardial injury and myocarditis are predictors of poor outcomes. Nonetheless, little is understood regarding SARS-CoV-2 tropism within the heart and whether cardiac complications result directly from myocardial infection. Here, we develop a human engineered heart tissue model and demonstrate that SARS-CoV-2 selectively infects cardiomyocytes. Viral infection is dependent on expression of angiotensin-I converting enzyme 2 (ACE2) and endosomal cysteine proteases, suggesting an endosomal mechanism of cell entry. After infection with SARS-CoV-2, engineered tissues display typical features of myocarditis, including cardiomyocyte cell death, impaired cardiac contractility, and innate immune cell activation. Consistent with these findings, autopsy tissue obtained from individuals with COVID-19 myocarditis demonstrated cardiomyocyte infection, cell death, and macrophage-predominate immune cell infiltrate. These findings establish human cardiomyocyte tropism for SARS-CoV-2 and provide an experimental platform for interrogating and mitigating cardiac complications of COVID-19. url: https://doi.org/10.1101/2020.11.04.364315 doi: 10.1101/2020.11.04.364315 id: cord-332271-slouuryl author: Baker, Jeremy D. title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease date: 2020-08-27 words: 2683.0 sentences: 172.0 pages: flesch: 52.0 cache: ./cache/cord-332271-slouuryl.txt txt: ./txt/cord-332271-slouuryl.txt summary: title: A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV-2 main protease Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing 27 as selective and potent inhibitors of SARS-CoV-2 Mpro. Taken together this work suggests previous large-scale commercial 35 drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some 36 previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for 37 rapid repurposing. Taken together this work suggests previous large-scale commercial 35 drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some 36 previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for 37 rapid repurposing. Before screening the Broad library, 100 we piloted our assay conditions against the NIH Clinical collections library (~650 compounds) and 101 calculated our Z''-factor for each plate at 0.780 and 0.784 (Fig 1C and D) . abstract: The SARS coronavirus type 2 (SARS-CoV-2) emerged in late 2019 as a zoonotic virus highly transmissible between humans that has caused the COVID-19 pandemic 1,2. This pandemic has the potential to disrupt healthcare globally and has already caused high levels of mortality, especially amongst the elderly. The overall case fatality rate for COVID-19 is estimated to be ∼2.3% overall 3 and 32.3% in hospitalized patients age 70-79 years 4. Therapeutic options for treating the underlying viremia in COVID-19 are presently limited by a lack of effective SARS-CoV-2 antiviral drugs, although steroidal anti-inflammatory treatment can be helpful. A variety of potential antiviral targets for SARS-CoV-2 have been considered including the spike protein and replicase. Based upon previous successful antiviral drug development for HIV-1 and hepatitis C, the SARS-CoV-2 main protease (Mpro) appears an attractive target for drug development. Here we show the existing pharmacopeia contains many drugs with potential for therapeutic repurposing as selective and potent inhibitors of SARS-CoV-2 Mpro. We screened a collection of ∼6,070 drugs with a previous history of use in humans for compounds that inhibit the activity of Mpro in vitro. In our primary screen we found ∼50 compounds with activity against Mpro (overall hit rate <0.75%). Subsequent dose validation studies demonstrated 8 dose responsive hits with an IC50 ≤ 50 μM. Hits from our screen are enriched with hepatitis C NS3/4A protease targeting drugs including Boceprevir (IC50=0.95 μM), Ciluprevir (20.77μM). Narlaprevir (IC50=1.10μM), and Telaprevir (15.25μM). These results demonstrate that some existing approved drugs can inhibit SARS-CoV-2 Mpro and that screen saturation of all approved drugs is both feasible and warranted. Taken together this work suggests previous large-scale commercial drug development initiatives targeting hepatitis C NS3/4A viral protease should be revisited because some previous lead compounds may be more potent against SARS-CoV-2 Mpro than Boceprevir and suitable for rapid repurposing. url: https://doi.org/10.1101/2020.07.10.197889 doi: 10.1101/2020.07.10.197889 id: cord-284627-qvz63m93 author: Banerjee, Shuvam title: Decoding the lethal effect of SARS-CoV-2 (novel coronavirus) strains from global perspective: molecular pathogenesis and evolutionary divergence date: 2020-04-09 words: 3691.0 sentences: 336.0 pages: flesch: 67.0 cache: ./cache/cord-284627-qvz63m93.txt txt: ./txt/cord-284627-qvz63m93.txt summary: The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. Interpretation The fatality outcome depends on three important factors (a) number of mutation (b) rarity of the allelic variation and (c) functional consequence of the mutation at protein level. 12, 14 In this study, we comprehensively analyzed the whole genome sequence homology from the available patient data uploaded by affected countries in NCBI Virus database, identified the mutations developed by different strains from the ancestor strain and studied the impact of those mutations at functional level. In summary, the present study reveals that the fatality rate increases with not only the number of mutations but also depending on its allelic rarity as well as functional alteration of protein. abstract: Background COVID-19 is a disease with global public health emergency that have shook the world since its’ first detection in China in December, 2019. Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) is the pathogen responsible behind this pandemic. The lethality of different viral strains is found to vary in different geographical locations but the molecular mechanism is yet to be known. Methods Available data of whole genome sequencing of different viral strains published by different countries were retrieved and then analysed using Multiple Sequence Alignment and Pair-wise Sequence Alignment leading to Phylogenetic tree construction. Each location and the corresponding genetic variations were screened in depth. Then the variations are analysed at protein level giving special emphasis on Non Synonymous amino acid substitutions. The fatality rates in different countries were matched against the mutation number, rarity of the nucleotide alterations and functional impact of the Non Synonymous changes at protein level, separately and in combination. Findings All the viral strains have been found to evolve from the viral strain of Taiwan (MT192759) which is 100% identical with the ancestor SARS-CoV-2 sequences of Wuhan (NC 045512.2; submitted on 5th Jan, 2020). Transition from C to T (C>T) is the most frequent mutation in this viral genome and mutations A>T, G>A, T>A are the rarest ones, found in countries with maximum fatality rate i.e Italy, Spain and Sweden. 20 Non Synonymous mutations are located in viral genome spanning Orf1ab polyprotein, Surface glycoprotein, Nucleocapsid protein etc. The functional effect on the structure and function of the protein can favourably or unfavourably interact with the host body. Interpretation The fatality outcome depends on three important factors (a) number of mutation (b) rarity of the allelic variation and (c) functional consequence of the mutation at protein level. The molecular divergence, evolved from the ancestral strain (S) lead to extremely lethal (E), lethal(L) and non lethal (N) strains with the involvement of an Intermediate strain(I). url: https://doi.org/10.1101/2020.04.06.027854 doi: 10.1101/2020.04.06.027854 id: cord-335075-6wo2o5pp author: Bangaru, Sandhya title: Structural analysis of full-length SARS-CoV-2 spike protein from an advanced vaccine candidate date: 2020-08-06 words: 4715.0 sentences: 240.0 pages: flesch: 51.0 cache: ./cache/cord-335075-6wo2o5pp.txt txt: ./txt/cord-335075-6wo2o5pp.txt summary: Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Site-specific glycosylation of the SARS-CoV-2 prefusion spike protein produced in SF9 insect cells was analyzed using our recently described mass spectrometry proteomics-based method, involving treatment with proteases followed by sequential treatment with the endoglycosidases (Endo H and PNGase F) to introduce mass signatures in peptides with N-linked sequons (Asn-X-Thr/Ser) to assess the extent of glycosylation and the degree of glycan processing from high mannose/hybrid type to complex type (24) . In this study, we performed structural analysis of the Novavax SARS-CoV We also observed two non-spike densities within the spike trimer that corresponded with linoleic acid and polysorbate 80 detergent. abstract: Vaccine efforts against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) responsible for the current COVID-19 pandemic are focused on SARS-CoV-2 spike glycoprotein, the primary target for neutralizing antibodies. Here, we performed cryo-EM and site-specific glycan analysis of one of the leading subunit vaccine candidates from Novavax based on a full-length spike protein formulated in polysorbate 80 (PS 80) detergent. Our studies reveal a stable prefusion conformation of the spike immunogen with slight differences in the S1 subunit compared to published spike ectodomain structures. Interestingly, we also observed novel interactions between the spike trimers allowing formation of higher order spike complexes. This study confirms the structural integrity of the full-length spike protein immunogen and provides a basis for interpreting immune responses to this multivalent nanoparticle immunogen. url: https://www.biorxiv.org/content/biorxiv/early/2020/08/06/2020.08.06.234674.full.pdf doi: 10.1101/2020.08.06.234674 id: cord-311445-b6bc6vwd author: Bansal, Kanika title: Codon pattern reveals SARS-CoV-2 to be a monomorphic strain that emerged through recombination of replicase and envelope alleles of bat and pangolin origin date: 2020-10-12 words: 2749.0 sentences: 169.0 pages: flesch: 60.0 cache: ./cache/cord-311445-b6bc6vwd.txt txt: ./txt/cord-311445-b6bc6vwd.txt summary: Systematic analysis of CUP of replicase (rdrp), spike, envelope (E), membrane glycoprotein (M), and nucleocapsid (N) encoding genes of SARS-CoV-2 from reported diverse lineages to suggest one-time host jump of a SARS-CoV-2 isolate into the human host. In contrast to human isolates, a high degree of variation in CUP of these genes suggests that bats, pangolins, and dogs are natural reservoirs of diverse strains. In the present study, we have focused on codon usage pattern (CUP) of SARS coronavirus from different hosts under debate (bat, pangolin, and dog) as a probable origin for SARS-CoV-2. However, another study comparing the codon usage pattern of SARS-CoV-2 with other betacoronaviruses suggested that current pandemic coronavirus is subjected to different evolutionary pressures (Gu et al., 2020) . The above analysis reveals single patterns for all five genes in different lineages of SARS-CoV-2 affirms a single event of host jump of codon-optimized SARS strain from its animal reservoir. abstract: Viruses are dependent on the host tRNA pool, and an optimum codon usage pattern (CUP) is a driving force in its evolution. Systematic analysis of CUP of replicase (rdrp), spike, envelope (E), membrane glycoprotein (M), and nucleocapsid (N) encoding genes of SARS-CoV-2 from reported diverse lineages to suggest one-time host jump of a SARS-CoV-2 isolate into the human host. In contrast to human isolates, a high degree of variation in CUP of these genes suggests that bats, pangolins, and dogs are natural reservoirs of diverse strains. At the same time, our analysis suggests that dogs are not a source of SARS-CoV-2. Interestingly, CUP of rdrp displays conservation with two bat SARS isolates RaTG13 and RmYN02. CUP of the SARS-CoV-2 E gene is also conserved with bat and pangolin isolates with variations for a few amino acids. This suggests role allele replacement in these two genes involving SARS strains of least two hosts. At the same time, a relatively conserved CUP pattern in replicase and envelope across hosts suggests them it to be an ideal target in antiviral development for SARS-CoV-2. url: https://doi.org/10.1101/2020.10.12.335521 doi: 10.1101/2020.10.12.335521 id: cord-311843-un6urdb1 author: Baray, Juwel Chandra title: BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response date: 2020-09-30 words: 3173.0 sentences: 230.0 pages: flesch: 62.0 cache: ./cache/cord-311843-un6urdb1.txt txt: ./txt/cord-311843-un6urdb1.txt summary: title: BANCOVID, the first D614G variant mRNA-based vaccine candidate against SARS-CoV-2 elicits neutralizing antibody and balanced cellular immune response The anti-sera and purified IgGs from immunized mice on day 7 and 14 neutralized SARS-CoV-2 pseudovirus in ACE2-expressing HEK293 cells in a dose dependent manner. The reactivity of the sera from each 221 group of mice immunized with BANCOVID was measured against SARS-CoV-2 S antigen 222 (SinoBiologicals, China). Analysis revealed IgG binding against SARS-CoV-2 S protein 223 antigens in the sera of the immunized mice. Flow cytometric analysis of total T cell (CD4 + ) populations producing TFN alpha on mouse splenocyte upon SARS-CoV-2 S protein stimulation. Flow cytometric analysis of total T cell (CD4 + ) populations producing IL-6 on mouse splenocyte upon SARS-CoV-2 S protein stimulation. Flow cytometric analysis of total T cell (CD4 + ) populations producing IL-6 on mouse splenocyte upon SARS-CoV-2 S protein stimulation. abstract: Effective vaccine against SARS-CoV-2 is the utmost importance in the current world. More than 1 million deaths are accounted for relevant pandemic disease COVID-19. Recent data showed that D614G genotype of the virus is highly infectious and responsible for almost all infection for 2nd wave. Despite of multiple vaccine development initiatives, there are currently no report that has addressed this critical variant D614G as vaccine candidate. Here we report the development of an mRNA-LNP vaccine considering the D614G variant and characterization of the vaccine in preclinical trial. The surface plasmon resonance (SPR) data with spike protein as probe and competitive neutralization with RBD and S2 domain revealed that immunization generated specific antibody pools against the whole extracellular domain (RBD and S2) of the spike protein. The anti-sera and purified IgGs from immunized mice on day 7 and 14 neutralized SARS-CoV-2 pseudovirus in ACE2-expressing HEK293 cells in a dose dependent manner. Importantly, immunization protected mice lungs from pseudovirus entry and cytopathy. The immunologic responses have been implicated by a balanced and stable population of CD4+ cells with a Th1 bias. The IgG2a to IgG1 and (IgG2a+IgG2b) to (IgG1+IgG3) ratios were found 1±0.2 and 1.24±0.1, respectively. These values are comparatively higher than relevant values for other published SARS-CoV-2 vaccine in development,1, 2 and suggesting higher viral clearance capacity for our vaccine. The data suggested great promise for immediate translation of the technology to the clinic. url: https://doi.org/10.1101/2020.09.29.319061 doi: 10.1101/2020.09.29.319061 id: cord-103208-krann2ir author: Barber-Axthelm, Isaac M title: Coformulation with tattoo ink for immunological assessment of vaccine immunogenicity in the draining lymph node date: 2020-08-29 words: 2931.0 sentences: 146.0 pages: flesch: 43.0 cache: ./cache/cord-103208-krann2ir.txt txt: ./txt/cord-103208-krann2ir.txt summary: In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. We tested if sampling accuracy, and the characterisation of vaccine-elicited immune responses ex vivo, could be improved using tattoo ink to label vaccine-draining LNs in NHPs. Pigtail macaques (Macaca nemastrina) were immunised in the right quadriceps with SARS-CoV-2 spike (100μg) formulated with monophosphoryl lipid A (MPLA) liposomal adjuvant ( 2 9 ) , and were boosted IM in the right and left quadriceps with SARS-CoV-2 spike (100μg) formulated with MPLA and tattoo ink (1.0%). . Animals were additionally immunised in the right and left deltoids with human immunodeficiency virus-1 (HIV-1) fixed trimeric envelope protein (SOSIP) vaccines (100μg) formulated with MPLA and 1.0% tattoo ink (ink in the right deltoid only), with expected drainage to the axillary LNs (Fig 3A) ( abstract: Characterisation of germinal centre B and T cell responses yields critical insights into vaccine immunogenicity. Non-human primates are a key pre-clinical animal model for human vaccine development, allowing both lymph node and circulating immune responses to be longitudinally sampled for correlates of vaccine efficacy. However, patterns of vaccine antigen drainage via the lymphatics after intramuscular immunisation can be stochastic, driving uneven deposition between lymphoid sites, and between individual lymph nodes within larger clusters. In order to improve the accurate isolation of antigen-exposed lymph nodes during biopsies and necropsies, we developed and validated a method for co-formulating candidate vaccines with tattoo ink, which allows for direct visual identification of vaccine-draining lymph nodes and evaluation of relevant antigen-specific B and T cell responses by flow cytometry. This approach improves the assessment of vaccine-induced immunity in highly relevant non-human primate models. url: https://doi.org/10.1101/2020.08.27.270975 doi: 10.1101/2020.08.27.270975 id: cord-347982-omxcdiwt author: Basso, Fernanda Gisele title: Cooperative efforts on developing vaccines and therapies for COVID-19 Cooperative efforts for COVID-19 date: 2020-09-06 words: 3433.0 sentences: 168.0 pages: flesch: 36.0 cache: ./cache/cord-347982-omxcdiwt.txt txt: ./txt/cord-347982-omxcdiwt.txt summary: The present research analyzes how the cooperation networks were set off considering the clinical trials on therapies and vaccines that were developed specifically to treat or prevent COVID-19. For the construction of cooperation networks, it was assumed that organizations signed agreements and/or treaties to develop specific studies, establishing joint ownership of the results and the new drug or vaccine, with the purpose of forming an alliance for innovation [20] . Regarding the distribution of the types of organizations that cooperate by category (Fig 3) , a greater diversity of partnerships was observed in antibodies, followed by vaccines and proteins, because these categories address complex therapies and require complementarity among several disciplines (e.g., adjuvants in Because clinical adoption and commercial success are due to the incorporation degree of existing practices in innovation processes [23] , the diffusion of disruptive technologies in this field may encounter greater challenges. abstract: Health organizations have always sought partnership to join competencies in innovation, even with fierce competition in this sector. In this pandemic moment it is relevant to observe how organizations behave to seek quick and safe answers. The present research analyzes how the cooperation networks were set off considering the clinical trials on therapies and vaccines that were developed specifically to treat or prevent COVID-19. Social Network Analysis technique was used to build cooperation networks and apply metrics that characterize these connections. There was an evaluation of statistics of Strength of cooperation and Unilateral dependence of cooperation that identify the cooperation strength between two organizations, and the dependence of this relations. A total of 415 clinical trial were identified, of which 42% are in cooperation. From organizations that have partnership, firms are the first, followed by universities. We extracted the main categories that concentrate 74% of partnerships in the trials of antibody, and vaccine. Several organizations cooperate in multiple categories of trials, evidencing the efforts to focus on different strategies to treat the disease. We found high strength of cooperation and an assimetryc dependency between partners, which can be assigned to specialized models of partnership and it occurs in competitive enviroments like this pandemic moment. Cooperation were not limited to geographical proximity and the advent of Chinese players can represent a new change in the biotechnological development axis. Finally, the challenge of finding therapeutic or immunological solutions for COVID-19 demonstrates a clear composition of cooperation groups that complement their skills to manage organizational strategies to beat the pandemic. In this new paradigm, there can be partnerships not only in clinical trial but also in pre-competitive technologies development. This experience is expected to change the way of organizations define their R&D strategies and start to adopt more a collaborative innovation model. url: https://doi.org/10.1101/2020.09.06.282145 doi: 10.1101/2020.09.06.282145 id: cord-330337-d41imvo7 author: Basu, Souradip title: Impact of clade specific mutations on structural fidelity of SARS-CoV-2 proteins date: 2020-10-20 words: 6428.0 sentences: 311.0 pages: flesch: 52.0 cache: ./cache/cord-330337-d41imvo7.txt txt: ./txt/cord-330337-d41imvo7.txt summary: Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. The secondary structure of the wild type and the mutant proteins along with their degree of disordered residues and accessible surface area was predicted using the primary sequence of the protein. Each of the seven proteins were assigned a score of either ''-1'' or ''0'', for each of the four computational tools used for epitope prediction, where ''-1'' corresponds to any change in number or binding efficacy of antigenic determinants, that may have surfaced because of mutation and ''0'' corresponds to no changes between wild type and mutant forms. I-Mutant2.0: predicting stability changes upon mutation from the protein sequence or structure abstract: The SARS-CoV-2 is a positive stranded RNA virus with a genome size of ~29.9 kilobase pairs which spans 29 open reading frames. Studies have revealed that the genome encodes about 16 non-structural proteins (nsp), four structural proteins, and six or seven accessory proteins. Based on prevalent knowledge on SARS-CoV and other coronaviruses, functions have been assigned for majority of the proteins. While, researchers across the globe are engrossed in identifying a potential pharmacological intervention to control the viral outbreak, none of the work has come up with new antiviral drugs or vaccines yet. One possible approach that has shown some positive results is by treating infected patients with the plasma collected from convalescent COVID-19 patients. Several vaccines around the world have entered their final trial phase in humans and we expect that these will in time be available for application to worldwide population to combat the disease. In this work we analyse the effect of prevalent mutations in the major pathogenesis related proteins of SARS-COV2 and attempt to pinpoint the effects of those mutations on the structural stability of the proteins. Our observations and analysis direct us to identify that all the major mutations have a negative impact in context of stability of the viral proteins under study and the mutant proteins suffer both structural and functional alterations as a result of the mutations. Our binary scoring scheme identifies L84S mutation in ORF8 as the most disruptive of the mutations under study. We believe that, the virus is under the influence of an evolutionary phenomenon similar to Muller’s ratchet where the continuous accumulation of these mutations is making the virus less virulent which may also explain the reduction in fatality rates worldwide. url: https://doi.org/10.1101/2020.10.20.347021 doi: 10.1101/2020.10.20.347021 id: cord-103715-53v1qoyc author: Bauman, Neda title: Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts date: 2020-05-21 words: 1028.0 sentences: 62.0 pages: flesch: 53.0 cache: ./cache/cord-103715-53v1qoyc.txt txt: ./txt/cord-103715-53v1qoyc.txt summary: title: Computational image analysis reveals the structural complexity of Toxoplasma gondii tissue cysts A novel approach to analyze the structure of in vivo-derived tissue cysts may be the increasingly used computational image analysis. gondii cysts by morphological, particle, and fractal analysis, as well as to determine if and how it is impacted by parasite strain, cyst age, and host factors. The parameters of interest included diameter, circularity, relative particle count (RPC), fractal dimension (FD), lacunarity, and packing density (PD). Cysts were transferred to black background images for subsequent particle analysis. In that manner, all of the cyst cross-section images were subjected to an 148 automated processing and the obtained particle numbers, N p , were expected to be proportional to the Fig 2C. Novel approaches reveal that Toxoplasma 357 gondii bradyzoites within tissue cysts are dynamic and replicating entities in vivo Vet S2 Data -Fractal dimension and lacunarity of tissue cysts (n=31) abstract: Toxoplasma gondii is an obligate intracellular parasite infecting up to one third of the human population. The central event in the pathogenesis of toxoplasmosis is the conversion of tachyzoites into encysted bradyzoites. A novel approach to analyze the structure of in vivo-derived tissue cysts may be the increasingly used computational image analysis. The objective of this study was to quantify the geometrical complexity of T. gondii cysts by morphological, particle, and fractal analysis, as well as to determine if and how it is impacted by parasite strain, cyst age, and host factors. Analyses were performed on 31 images of T. gondii brain cysts of four type-2 strains (the reference Me49 strain and three local isolates, named BGD1, BGD14, and BGD26) using ImageJ software package. The parameters of interest included diameter, circularity, relative particle count (RPC), fractal dimension (FD), lacunarity, and packing density (PD). Although cyst diameter varied widely, its negative correlation with RPC was observed. Circularity was remarkably close to 1, indicating that the shape of the brain cysts was a perfect circle. RPC, FD, and PD did not vary among cysts of different strains, age, and derived from mice of different genetic background. Conversely, lacunarity, which is a measure of heterogeneity, was significantly lower for BGD1 strain vs. all other strains, and higher for Me49 vs. BGD14 and BGD26, but did not differ among Me49 cysts of different age, and derived from genetically different mice. This study is the first application of fractal analysis in describing the structural complexity of T. gondii cysts. Despite all the differences among the analyzed cysts, most parameters remained conserved. Fractal analysis is a novel and widely accessible approach, which along with particle analysis may be applied to gain further insight into T. gondii cyst morphology. url: https://doi.org/10.1101/2020.05.21.108118 doi: 10.1101/2020.05.21.108118 id: cord-102811-jlr4vb4u author: Baumeister, Sebastian E title: Physical activity and risk of Alzheimer’s disease: a two-sample Mendelian randomization study date: 2019-10-29 words: 2194.0 sentences: 111.0 pages: flesch: 38.0 cache: ./cache/cord-102811-jlr4vb4u.txt txt: ./txt/cord-102811-jlr4vb4u.txt summary: Several meta-analyses of observational studies suggested a protective effect of physical activity for cognitive decline and risk of dementia and AD [3] [4] [5] [6] [7] [8] [9] [10] . Mendelian randomization (MR) is a method that uses genetic variants as instrumental variables to uncover causal relationships in the presence of observational study bias such as unobserved confounding and reverse causation [15] . We selected eight SNPs associated with accelerometer-based physical activity (mean acceleration in milli-gravities) at a genome-wide significance level (P < 5 x 10 -8 ), using a PLINKclumping algorithm (r² threshold = 0.001 and window size = 10mB), from a genome-wide study of 91,084 UK Biobank participants [16] (Supplementary Table 1 ). Summary data for the association of SNPs for accelerometer-based physical activity with AD were obtained from a GWAS of 21,982 clinically-confirmed AD cases and 41,944 cognitively normal controls [17] . Physical activity can improve cognition in patients with Alzheimer''s disease: a systematic review and meta-analysis of randomized controlled trials abstract: Introduction Evidence from observational studies for the effect of physical activity on the risk of Alzheimer’s disease (AD) is inconclusive. We performed Mendelian randomization analysis to examine whether physical activity is a protective factor for AD. Methods Summary data of genome-wide association studies on physical activity and AD were identified using PubMed and the GWAS catalog. The study population included 21,982 AD cases and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNP) known at P < 5×10−8 to be associated with accelerometer-assessed physical activity served as instrumental variables. Results Genetically predicted accelerometer-assessed physical activity had no effect on the risk of AD (inverse variance weighted odds ratio [OR] per standard deviation (SD) increment: 1.03, 95% confidence interval: 0.97-1.10, P=0.332). Discussion The present study does not support a relationship between physical activity and risk of AD, and suggests that previous observational studies might have been biased. url: https://doi.org/10.1101/819821 doi: 10.1101/819821 id: cord-348727-o38uplxe author: Beaudoin-Bussières, Guillaume title: Decline of humoral responses against SARS-CoV-2 Spike in convalescent individuals date: 2020-07-09 words: 920.0 sentences: 63.0 pages: flesch: 54.0 cache: ./cache/cord-348727-o38uplxe.txt txt: ./txt/cord-348727-o38uplxe.txt summary: Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. Neutralizing activity against pseudoparticles bearing the SARS-CoV S 120 glycoprotein was detected in only 25% of convalescent plasma and exhibited low potency, as 121 previously reported (Figure 2) (14) . Of note, while we observed enhanced infectivity for the 122 D614G variant compared to its WT SARS-CoV-2 S counterpart ( Figure S3A ), no major 123 differences in neutralization with convalescent plasma were detected at both time-points ( Figure 124 S3B), thus suggesting that the D614G change does not affect the overall conformation of the 125 Spike, in agreement with recent findings (18) . 126 127 The capacity to neutralize SARS-CoV-2 S WT or D614G-pseudotyped particles 128 significantly correlated with the presence of RBD-specific IgG, IgM and anti-S antibodies 129 ( Figure S4 ). Interestingly, we observed a pronounced decrease (20-30%) in the percentage of 130 patients able to neutralize pseudoparticles bearing SARS-CoV-2 S glycoprotein between 6 and 131 10 weeks after symptoms onset. abstract: In the absence of effective vaccines and with limited therapeutic options, convalescent plasma is being collected across the globe for potential transfusion to COVID-19 patients. The therapy has been deemed safe and several clinical trials assessing its efficacy are ongoing. While it remains to be formally proven, the presence of neutralizing antibodies is thought to play a positive role in the efficacy of this treatment. Indeed, neutralizing titers of ≥1:160 have been recommended in some convalescent plasma trials for inclusion. Here we performed repeated analyses at one-month interval on 31 convalescent individuals to evaluate how the humoral responses against the SARS-CoV-2 Spike, including neutralization, evolve over time. We observed that receptor-binding domain (RBD)-specific IgG slightly decreased between six and ten weeks after symptoms onset but RBD-specific IgM decreased much more abruptly. Similarly, we observed a significant decrease in the capacity of convalescent plasma to neutralize pseudoparticles bearing SARS-CoV-2 S wild-type or its D614G variant. If neutralization activity proves to be an important factor in the clinical efficacy of convalescent plasma transfer, our results suggest that plasma from convalescent donors should be recovered rapidly after symptoms resolution. url: https://doi.org/10.1101/2020.07.09.194639 doi: 10.1101/2020.07.09.194639 id: cord-318499-uihof6k6 author: Beddingfield, Brandon title: The Integrin Binding Peptide, ATN-161, as a Novel Therapy for SARS-CoV-2 Infection date: 2020-06-16 words: 1550.0 sentences: 100.0 pages: flesch: 54.0 cache: ./cache/cord-318499-uihof6k6.txt txt: ./txt/cord-318499-uihof6k6.txt summary: Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting ACE2 binding with the SARS-CoV-2 spike protein. This work focuses on the potential to inhibit SARS-CoV-2 entry through a hypothesized α5β1integrin-based mechanism, and indicates that inhibiting α5β1 integrin interaction with ACE2 and the spike protein using a novel molecule ATN-161 represents a promising approach to treat COVID-19. In order to assess disruption of binding of α5β1 to SARS-CoV-2 Spike protein, 96-well plates were coated as before, but incubation with ATN-161 was performed in conjunction with 1µg/mL spike (produced under HHSN272201400008C and obtained through BEI Resources, NIAID, NIH: Spike Glycoprotein Receptor Binding Domain (RBD) from SARS-Related Coronavirus 2, Wuhan-Hu-1, Recombinant from HEK293 Cells, NR-52306) in the presence of 1mM MnCl2, followed by detection with an anti-spike antibody. Inhibition of SARS-CoV-2 spike protein binding to human ACE2 by ATN-161. abstract: Many efforts to design and screen therapeutics for the current severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic have focused on inhibiting viral host cell entry by disrupting ACE2 binding with the SARS-CoV-2 spike protein. This work focuses on the potential to inhibit SARS-CoV-2 entry through a hypothesized α5β1integrin-based mechanism, and indicates that inhibiting α5β1 integrin interaction with ACE2 and the spike protein using a novel molecule ATN-161 represents a promising approach to treat COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32587959/ doi: 10.1101/2020.06.15.153387 id: cord-262573-wdgbno9p author: Begum, Feroza title: Analyses of spike protein from first deposited sequences of SARS-CoV2 from West Bengal, India date: 2020-05-03 words: 1615.0 sentences: 96.0 pages: flesch: 60.0 cache: ./cache/cord-262573-wdgbno9p.txt txt: ./txt/cord-262573-wdgbno9p.txt summary: We report one unique mutation at position 723 and the other at 1124 in the S2 domain of spike protein of the isolates from West Bengal only and one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western part of India). We downloaded the five new SARS-CoV2 sequences from West Bengal (EPI_ISL_430468; EPI_ISL_430467; EPI_ISL_430465; EPI_ISL_430464; EPI_ISL_430466) from GISAID database and the spike protein sequences corresponding to Kerala isolates [2] and Gujarat isolate [3] from the NCBI virus database. Since, currently we have sequences against SARS-CoV2 only from three states in India i.e. Kerala, Gujarat and now West Bengal, we compared all the sequences to detect possible changes ( Figure 2) . This is the first report of mutations of such types in the isolates of the state of West Bengal and further sequencing followed by sequence analyses would help expanding the knowledge about variations of spike protein in human SARS-CoV. abstract: India has recently started sequencing SARS-CoV2 genome from clinical isolates. Currently only few sequences are available from three states in India. Kerala was the first state to deposit complete sequence from two isolates followed by one from Gujarat. On April 27, 2020, the first five sequences from the state of West Bengal (Eastern India) were deposited on ‘a global initiative on sharing avian flu data’ (GISAID) platform. In this paper we have analysed the spike protein sequences from all these five isolates and also compared for their similarities or differences with other sequences reported in India and with isolates of Wuhan origin. We report one unique mutation at position 723 and the other at 1124 in the S2 domain of spike protein of the isolates from West Bengal only and one mutation downstream of the receptor binding domain at position 614 in S1 domain which was common with the sequence from Gujarat (a state of western part of India). Mutation in the S2 domain showed changes in the secondary structure of the spike protein at region of mutation. We also studied molecular dynamics using normal mode analyses and found that this mutation decreases the flexibility of S2 domain. Since both S1 and S2 are important in receptor binding followed by entry in the host cells, such mutations may define the affinity or avidity of receptor binding. url: https://doi.org/10.1101/2020.04.28.066985 doi: 10.1101/2020.04.28.066985 id: cord-281565-v8s2ski3 author: Belmonte-Reche, Efres title: Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2 date: 2020-08-20 words: 4545.0 sentences: 253.0 pages: flesch: 53.0 cache: ./cache/cord-281565-v8s2ski3.txt txt: ./txt/cord-281565-v8s2ski3.txt summary: These PQS and PiMS have been assessed according to their potential to form, uniqueness, frequency of appearance, conservation rates between 3297 different 2019-nCoV clinical cases, confirmed quadruplex-forming sequence presence and localization within the genome. Then, these PQS and PiMS were evaluated by their frequency of appearance in the corresponding genome, the presence of known-to-form quadruplex structures sequences within and their probability of quadruplex-formation score (as the mean of G4Hunter (52) and the adaptation of the PQSfinder algorithm (53) ). A flexible configuration of quadruplex definitions will detect larger amounts of candidates at the expense of requiring more computing power and accepting sequences that are more ambiguous in forming quadruplex structures in vitro (as determined by their score; with longer loops, smaller runs, more bulges and more complementary G/C %, Figure 1 , B). Expanding the search for common candidates to the entire virus realm, we matched one PQS and PiMS from the 2019-nCoV with the potential quadruplexes found in four viruses from abstract: In this paper we report the analysis of the 2019-nCoV genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for 2019-nCoV. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, hundreds of potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over three thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were compared sequentially to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire realm. Sequences found in common with other species were further analyzed and characterized. Sequences with high scores unique to the 2019-nCoV were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates was then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable theranostic targets against the 2019-nCoV. GRAPHICAL ABSTRACT url: https://doi.org/10.1101/2020.08.19.257493 doi: 10.1101/2020.08.19.257493 id: cord-291156-zxg3dsm3 author: Bernasconi, Anna title: Empowering Virus Sequences Research through Conceptual Modeling date: 2020-05-01 words: 4600.0 sentences: 206.0 pages: flesch: 38.0 cache: ./cache/cord-291156-zxg3dsm3.txt txt: ./txt/cord-291156-zxg3dsm3.txt summary: We hereby present the Viral Conceptual Model (VCM), centered on the virus sequence and described from four perspectives: biological (virus type and hosts/sample), analytical (annotations and variants), organizational (sequencing project) and technical (experimental technology). -We propose a new Viral Conceptual Model (VCM), a general conceptual model for describing viral sequences, organized along specific dimensions that highlight a conceptual schema similar to GCM [6] ; -Focusing on SARS-CoV2, we show how VCM can be profitably linked to a phenotype database with information on COVID-19 infected patients; -We provide a list of interesting queries replicating newly released literature on infectious diseases; these can be easily performed on VCM. Some interesting portals have become interfaces to GISAID data with particular focuses: NextStrain [18] overviews emergent viral outbreaks based on the visualization of sequence data integrated with geographic information, serology, and host species; CoV-GLUE, 9 part of the GLUE suite [38] , contains a database of replacements, insertions and deletions observed in sequences sampled from the pandemic. abstract: The pandemic outbreak of the coronavirus disease has attracted attention towards the genetic mechanisms of viruses. We hereby present the Viral Conceptual Model (VCM), centered on the virus sequence and described from four perspectives: biological (virus type and hosts/sample), analytical (annotations and variants), organizational (sequencing project) and technical (experimental technology). VCM is inspired by GCM, our previously developed Genomic Conceptual Model, but it introduces many novel concepts, as viral sequences significantly differ from human genomes. When applied to SARS-CoV2 virus, complex conceptual queries upon VCM are able to replicate the search results of recent articles, hence demonstrating huge potential in supporting virology research. In addition to VCM, we also illustrate the data dictionary for patient’s phenotype used by the COVID-19 Host Genetic Initiative. Our effort is part of a broad vision: availability of conceptual models for both human genomics and viruses will provide important opportunities for research, especially if interconnected by the same human being, playing the role of virus host as well as provider of genomic and phenotype information. url: https://doi.org/10.1101/2020.04.29.067637 doi: 10.1101/2020.04.29.067637 id: cord-355758-tk7eturq author: Berrio, Alejandro title: Positive selection within the genomes of SARS-CoV-2 and other Coronaviruses independent of impact on protein function date: 2020-09-22 words: 2175.0 sentences: 156.0 pages: flesch: 49.0 cache: ./cache/cord-355758-tk7eturq.txt txt: ./txt/cord-355758-tk7eturq.txt summary: Background The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease (COVID-19) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein based on the ratio of synonymous to nonsynonymous substitution. In addition, we find other likely targets of positive selection within the genome of SARS-CoV-2, specifically within the genes encoding Nsp4 and Nsp16. In Importantly, we also detected signals of positive selection in two additional regions of the 414 SARS-CoV-2 genome, specifically within the genes encoding Nsp4 and Nsp16 (Fig 1A) . Comparative analysis of coronavirus genomic RNA structure reveals 718 conservation in SARS-like coronaviruses. abstract: Background The emergence of a novel coronavirus (SARS-CoV-2) associated with severe acute respiratory disease (COVID-19) has prompted efforts to understand the genetic basis for its unique characteristics and its jump from non-primate hosts to humans. Tests for positive selection can identify apparently nonrandom patterns of mutation accumulation within genomes, highlighting regions where molecular function may have changed during the origin of a species. Several recent studies of the SARS-CoV-2 genome have identified signals of conservation and positive selection within the gene encoding Spike protein based on the ratio of synonymous to nonsynonymous substitution. Such tests cannot, however, detect changes in the function of RNA molecules. Methods Here we apply a test for branch-specific oversubstitution of mutations within narrow windows of the genome without reference to the genetic code. Results We recapitulate the finding that the gene encoding Spike protein has been a target of both purifying and positive selection. In addition, we find other likely targets of positive selection within the genome of SARS-CoV-2, specifically within the genes encoding Nsp4 and Nsp16. Homology-directed modeling indicates no change in either Nsp4 or Nsp16 protein structure relative to the most recent common ancestor. Thermodynamic modeling of RNA stability and structure, however, indicates that RNA secondary structure within both genes in the SARS-CoV-2 genome differs from those of RaTG13, the reconstructed common ancestor, and Pan-CoV-GD (Guangdong). These SARS-CoV-2-specific mutations may affect molecular processes mediated by the positive or negative RNA molecules, including transcription, translation, RNA stability, and evasion of the host innate immune system. Our results highlight the importance of considering mutations in viral genomes not only from the perspective of their impact on protein structure, but also how they may impact other molecular processes critical to the viral life cycle. url: https://doi.org/10.1101/2020.09.16.300038 doi: 10.1101/2020.09.16.300038 id: cord-284191-05djnz4p author: Bert, Nina Le title: Different pattern of pre-existing SARS-COV-2 specific T cell immunity in SARS-recovered and uninfected individuals date: 2020-05-27 words: 1944.0 sentences: 103.0 pages: flesch: 53.0 cache: ./cache/cord-284191-05djnz4p.txt txt: ./txt/cord-284191-05djnz4p.txt summary: To study SARS-CoV-2 specific T cells associated with viral clearance, we collected peripheral blood of 24 individuals who recovered from mild to severe COVID-19 (demographic, clinical and virological information are summarized in Extended Data Table 1 ) and studied the T cell response against selected structural (nucleocapsid protein-NP) and non-structural proteins (NSP7 and NSP13 of ORF1) of the large SARS-CoV-2 proteome ( Figure 1A) . To confirm and further delineate the multispecificity of the NP-specific T cell response detected ex vivo in COVID-19 recovered patients, we defined in nine individuals, the distinctive sections of NP targeted by T cells. This is consistent with the findings of Grifoni et al 11 : using selected peptides, they detected ORF-1 specific T preferentially in some SARS-CoV-2 unexposed donors while T cells of COVID-19 recovered donors preferentially recognized structural proteins. Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals abstract: Memory T cells induced by previous infections can influence the course of new viral infections. Little is known about the pattern of SARS-CoV-2 specific pre-existing memory T cells in human. Here, we first studied T cell responses to structural (nucleocapsid protein, NP) and non-structural (NSP-7 and NSP13 of ORF1) regions of SARS-CoV-2 in convalescent from COVID-19 (n=24). In all of them we demonstrated the presence of CD4 and CD8 T cells recognizing multiple regions of the NP protein. We then show that SARS-recovered patients (n=23), 17 years after the 2003 outbreak, still possess long-lasting memory T cells reactive to SARS-NP, which displayed robust cross-reactivity to SARS-CoV-2 NP. Surprisingly, we observed a differential pattern of SARS-CoV-2 specific T cell immunodominance in individuals with no history of SARS, COVID-19 or contact with SARS/COVID-19 patients (n=18). Half of them (9/18) possess T cells targeting the ORF-1 coded proteins NSP7 and 13, which were rarely detected in COVID-19- and SARS-recovered patients. Epitope characterization of NSP7-specific T cells showed recognition of protein fragments with low homology to “common cold” human coronaviruses but conserved among animal betacoranaviruses. Thus, infection with betacoronaviruses induces strong and long-lasting T cell immunity to the structural protein NP. Understanding how pre-existing ORF-1-specific T cells present in the general population impact susceptibility and pathogenesis of SARS-CoV-2 infection is of paramount importance for the management of the current COVID-19 pandemic. url: https://doi.org/10.1101/2020.05.26.115832 doi: 10.1101/2020.05.26.115832 id: cord-102866-40s64455 author: Bhadra, Sanchita title: One enzyme reverse transcription qPCR using Taq DNA polymerase date: 2020-05-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Taq DNA polymerase, one of the first thermostable DNA polymerases to be discovered, has been typecast as a DNA-dependent DNA polymerase commonly employed for PCR. However, Taq polymerase belongs to the same DNA polymerase superfamily as the Molony murine leukemia virus reverse transcriptase and has in the past been shown to possess reverse transcriptase activity. We report optimized buffer and salt compositions that promote the reverse transcriptase activity of Taq DNA polymerase, and thereby allow it to be used as the sole enzyme in TaqMan RT-qPCR reactions. We demonstrate the utility of Taq-alone RT-qPCR reactions by executing CDC SARS-CoV-2 N1, N2, and N3 TaqMan RT-qPCR assays that could detect as few as 2 copies/µL of input viral genomic RNA. url: https://doi.org/10.1101/2020.05.27.120238 doi: 10.1101/2020.05.27.120238 id: cord-103320-2rpr7aph author: Bhandari, Bikash K. title: Solubility-Weighted Index: fast and accurate prediction of protein solubility date: 2020-03-26 words: 4889.0 sentences: 333.0 pages: flesch: 50.0 cache: ./cache/cord-103320-2rpr7aph.txt txt: ./txt/cord-103320-2rpr7aph.txt summary: Results We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli. Protein solubility, at least in part, depends upon extrinsic factors such as ionic strength, temperature and pH, as well as intrinsic factors-the physicochemical properties of the protein sequence and structure, including molecular weight, amino acid composition, hydrophobicity, aromaticity, isoelectric point, structural propensities and the polarity of surface residues (Wilkinson and Harrison 1991; Chiti et al. 2003 ) Among these sets of B-factors, sequence composition scoring using the most recently published set of normalised B-factors produced the highest AUC score ( To improve the prediction accuracy of solubility, we iteratively refined the weights of amino acid residues using the Nelder-Mead optimisation algorithm (Nelder and Mead 1965) . To understand the properties of soluble and insoluble proteins, we determined the enrichment of amino acid residues in the PSI:Biology targets relative to the eSOL sequences (see Methods). abstract: Motivation Recombinant protein production is a widely used technique in the biotechnology and biomedical industries, yet only a quarter of target proteins are soluble and can therefore be purified. Results We have discovered that global structural flexibility, which can be modeled by normalised B-factors, accurately predicts the solubility of 12,216 recombinant proteins expressed in Escherichia coli. We have optimised B-factors, and derived a new set of values for solubility scoring that further improves prediction accuracy. We call this new predictor the ‘Solubility-Weighted Index’ (SWI). Importantly, SWI outperforms many existing protein solubility prediction tools. Furthermore, we have developed ‘SoDoPE’ (Soluble Domain for Protein Expression), a web interface that allows users to choose a protein region of interest for predicting and maximising both protein expression and solubility. Availability The SoDoPE web server and source code are freely available at https://tisigner.com/sodope and https://github.com/Gardner-BinfLab/TISIGNER-ReactJS, respectively. The code and data for reproducing our analysis can be found at https://github.com/Gardner-BinfLab/SoDoPE_paper2020. url: https://doi.org/10.1101/2020.02.15.951012 doi: 10.1101/2020.02.15.951012 id: cord-326441-w8iyh59u author: Bhattacharjee, Sayan title: Transmission of allosteric response within the homotrimer of SARS-CoV-2 spike upon recognition of ACE2 receptor by the receptor-binding domain date: 2020-09-06 words: 2426.0 sentences: 129.0 pages: flesch: 48.0 cache: ./cache/cord-326441-w8iyh59u.txt txt: ./txt/cord-326441-w8iyh59u.txt summary: The pathogenesis of novel SARS-CoV-2 virus initiates through recognition of ACE2 receptor (Angiotensin-converting enzyme 2) of the host cells by the receptor-binding domain (RBD) located at spikes of the virus. Using MD simulations, we have demonstrated allosteric crosstalk within RBD in apoand receptor-bound states where dynamic correlated motions and electrostatic energy perturbations contribute. To probe deeper into the dynamicity of free and ACE2-bound RBD of the COVID spike protein, Cα atoms based root mean square fluctuations (RMSF) and Order parameter (S 2 ) considering the N-H vectors 9 of RBD, were calculated from the corresponding trajectories. The residue wise non-bonded interaction energy between free RBD and its bound state with ACE2 was described as: Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor abstract: The pathogenesis of novel SARS-CoV-2 virus initiates through recognition of ACE2 receptor (Angiotensin-converting enzyme 2) of the host cells by the receptor-binding domain (RBD) located at spikes of the virus. Following receptor-recognition, proteolytic cleavage between S1 and S2 subunits of the spike protein occurs with subsequent release of fusion peptide. Here, we report our study on allosteric communication within RBD that propagates the signal from ACE2-binding site towards allosteric site for the post-binding activation of proteolytic cleavage. Using MD simulations, we have demonstrated allosteric crosstalk within RBD in apo- and receptor-bound states where dynamic correlated motions and electrostatic energy perturbations contribute. While allostery, based on correlated motions, dominates inherent distal communication in apo-RBD, electrostatic energy perturbations determine favorable crosstalk within RBD upon binding to ACE2. Notably, allosteric path is constituted with evolutionarily conserved residues pointing towards their biological relevance. As revealed from recent structures, in the trimeric arrangement of spike, RBD of one copy interacts with S2 domain of another copy. Interestingly, the allosteric site identified is in direct contact (H-bonded) with a region in RBD that corresponds to the interacting region of RBD of one copy with S2 of another copy in trimeric constitution. Apparently, inter-monomer allosteric communication orchestrates concerted action of the trimer. Based on our results, we propose the allosteric loop of RBD as a potential drug target. url: https://doi.org/10.1101/2020.09.06.284901 doi: 10.1101/2020.09.06.284901 id: cord-260352-rhd0qqyn author: Bhattacharyya, Sumit title: Increased Expression of Chondroitin Sulfotransferases following AngII may Contribute to Pathophysiology Underlying Covid-19 Respiratory Failure: Impact may be Exacerbated by Decline in Arylsulfatase B Activity date: 2020-06-25 words: 2739.0 sentences: 162.0 pages: flesch: 50.0 cache: ./cache/cord-260352-rhd0qqyn.txt txt: ./txt/cord-260352-rhd0qqyn.txt summary: CHST15 (N-acetylgalactosamine 4ARSB activation requires oxygen for post-translational modification and activation, and ARSB activity is lower in hypoxic conditions [12, 13] ; b) decline in ARSB is associated with increased IL-6 expression in human bronchial epithelial cells and in patients with cystic fibrosis and asthma [14] ; c) decline in ARSB replicates effects of hypoxia and generation of sulfate by ARSB may be important in mitochondrial metabolism [12, 15] ; d) accumulation of sulfated glycosaminoglycans when ARSB is reduced can contribute to inflammation and pulmonary pathophysiology, as in cystic fibrosis [16] ; e) in patients with moderate COPD, refractoriness to oxygen therapy was associated with gene mutations regulating ARSB expression [17] ; and f) changes in chondroitin 4-sulfation affect binding of the critical molecules galectin-3 and SHP2 (PTPN11; protein tyrosine phosphatase non-receptor type 11) with impact on transcriptional events and vital cell signaling [18, 19] . abstract: The spike protein of SARS-CoV-2 binds to respiratory epithelium through the ACE2 receptor, an endogenous receptor for Angiotensin II (AngII). The mechanisms by which this viral infection leads to hypoxia and respiratory failure have not yet been elucidated. Interactions between the sulfated glycosaminoglycans heparin and heparan sulfate and the SARS-CoV-2 spike glycoprotein have been identified as participating in viral adherence and infectivity. In this brief report, we present data indicating that stimulation of vascular smooth muscle cells by AngII leads to increased expression of two chondroitin sulfotransferases (CHST11 and CHST15), which are required for the synthesis of the sulfated glycosaminoglycans chondroitin 4-sulfate (C4S) and chondroitin 4,6-disulfate (CSE). We suggest that increased expression of these chondroitin sulfotransferases and the ensuing production of chondroitin sulfates may contribute to viral adherence to bronchioalveolar cells and to the progression of respiratory disease in Covid-19. The enzyme Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase), which removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate residues, is required for degradation of C4S and CSE. In hypoxic conditions or following treatment with chloroquine, ARSB activity is reduced. Decline in ARSB can contribute to ongoing accumulation and airway obstruction by C4S and CSE. Decline in ARSB leads to increased expression of Interleukin(IL)-6 in human bronchial epithelial cells, and IL-6 is associated with cytokine storm in Covid-19. These findings indicate how chondroitin sulfates, chondroitin sulfotransferases, and chondroitin sulfatases may participate in the progression of hypoxic respiratory insufficiency in Covid-19 disease and suggest new therapeutic targets. url: https://doi.org/10.1101/2020.06.25.171975 doi: 10.1101/2020.06.25.171975 id: cord-259261-fmuozy3w author: Bickler, Stephen W. title: AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE date: 2020-06-16 words: 2039.0 sentences: 130.0 pages: flesch: 55.0 cache: ./cache/cord-259261-fmuozy3w.txt txt: ./txt/cord-259261-fmuozy3w.txt summary: title: AGE IS ASSOCIATED WITH INCREASED EXPRESSION OF PATTERN RECOGNITION RECEPTOR GENES AND ACE2, THE RECEPTOR FOR SARS-COV-2: IMPLICATIONS FOR THE EPIDEMIOLOGY OF COVID-19 DISEASE Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. We also asked the question if the differentially expressed genes between the oldest and youngest age groups encode proteins that interact with SARS-CoV-2 (see "Methods" section). Our analysis revealed eleven differentially expressed genes between the oldest and youngest age groups that encode proteins known to interact with SARS-CoV-2 (Fig. 3d) . Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts we show that expression of PRR genes and ACE2, the receptor for SARS-CoV-2 vary with age. abstract: Older aged adults and those with pre-existing conditions are at highest risk for severe COVID-19 associated outcomes. Using a large dataset of genome-wide RNA-seq profiles derived from human dermal fibroblasts (GSE113957) we investigated whether age affects the expression of pattern recognition receptor (PRR) genes and ACE2, the receptor for SARS-CoV-2. Older age was associated with increased expression of PRR genes, ACE2 and four genes that encode proteins that have been shown to interact with SAR2-CoV-2 proteins. Assessment of PRR expression might provide a strategy for stratifying the risk of severe COVID-19 disease at both the individual and population levels. url: https://doi.org/10.1101/2020.06.15.134403 doi: 10.1101/2020.06.15.134403 id: cord-265453-z6aux01t author: Bierig, Tobias title: Design, expression, purification and characterization of a YFP-tagged 2019-nCoV spike receptor-binding domain construct date: 2020-09-29 words: 3438.0 sentences: 183.0 pages: flesch: 58.0 cache: ./cache/cord-265453-z6aux01t.txt txt: ./txt/cord-265453-z6aux01t.txt summary: The receptor-binding domain (RBD) of the 2019-nCoV spike (S) protein contains disulfide bonds and N-linked glycosylations, therefore, it is typically produced by secretion. Here, we describe a construct and protocol for the expression and purification of yellow fluorescent protein (YFP) labeled 2019-nCoV spike RBD. The fusion protein, in the vector pcDNA 4/TO, comprises an N-terminal interferon alpha 2 (IFNα2) signal peptide, an eYFP, a FLAG-tag, a human rhinovirus 3C protease cleavage site, the RBD of the 2019-nCoV spike protein and a C-terminal 8x His-tag. Our experiments confirmed that the fusion protein (also after proteolytic removal of YFP) binds the human ACE2 peptidase domain. Ni-NTA IMAC After removal of detached cells by centrifugation, the expression medium containing the secreted fusion protein was supplemented with 1/4 tablet of protease inhibitor (complete EDTA-free protease inhibitor cocktail tablets, Roche Diagnostic GmbH, 45148300) and transferred to a 15 ml Falcon tube containing 200 l of washed, pre-equilibrated Ni-NTA agarose (Qiagen Cat. No. abstract: 2019-nCoV is the causative agent of the serious, still ongoing, worldwide COVID-19 pandemic. High quality recombinant virus proteins are required for research related to the development of vaccines and improved assays, and to the general understanding of virus action. The receptor-binding domain (RBD) of the 2019-nCoV spike (S) protein contains disulfide bonds and N-linked glycosylations, therefore, it is typically produced by secretion. Here, we describe a construct and protocol for the expression and purification of yellow fluorescent protein (YFP) labeled 2019-nCoV spike RBD. The fusion protein, in the vector pcDNA 4/TO, comprises an N-terminal interferon alpha 2 (IFNα2) signal peptide, an eYFP, a FLAG-tag, a human rhinovirus 3C protease cleavage site, the RBD of the 2019-nCoV spike protein and a C-terminal 8x His-tag. We stably transfected HEK 293 cells. Following expansion of the cells, the fusion protein was secreted from adherent cells into serum-free medium. Ni-NTA IMAC purification resulted in very high protein purity, based on analysis by SDS-PAGE. The fusion protein was soluble and monodisperse, as confirmed by size-exclusion chromatography (SEC) and negative staining electron microscopy. Deglycosylation experiments confirmed the presence of N-linked glycosylations in the secreted protein. Complex formation with the peptidase domain of human angiotensin-converting enzyme 2 (ACE2), the receptor for the 2019-nCoV spike RBD, was confirmed by SEC, both for the YFP-fused spike RBD and for spike RBD alone, after removal of YFP by proteolytic cleavage. Possible applications for the fusion protein include binding studies on cells or in vitro, fluorescent labeling of potential virus-binding sites on cells, the use as an antigen for immunization studies or as a tool for the development of novel virus- or antibody-detection assays. url: https://doi.org/10.1101/2020.09.29.318196 doi: 10.1101/2020.09.29.318196 id: cord-272513-umuiovrd author: Bindayna, Khalid Mubarak title: Variant analysis of SARS-CoV-2 genomes in the Middle East date: 2020-10-09 words: 3033.0 sentences: 217.0 pages: flesch: 59.0 cache: ./cache/cord-272513-umuiovrd.txt txt: ./txt/cord-272513-umuiovrd.txt summary: We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19. Methods The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID). Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East. • Our hypothesis is that variants found in SARS-CoV-2 genomes from Middle Eastern samples will indicate delivery from Iran. • The aim is to explore the structure of Middle Eastern genome strains using multiple sequence alignment, tree generation and variant prediction (and others). abstract: Background Coronavirus (COVID-19) was introduced into society in late 2019 and has now reached over 26 million cases and 850,000 deaths. The Middle East has a death toll of ∼50,000 and over 20,000 of these are in Iran, which has over 350,000 confirmed cases. We expect that Iranian cases caused outbreaks in the neighbouring countries and that variant mapping and phylogenetic analysis can be used to prove this. We also aim to analyse the variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) to characterise the common genome variants and provide useful data in the global effort to prevent further spread of COVID-19. Methods The approach uses bioinformatics approaches including multiple sequence alignment, variant calling and annotation and phylogenetic analysis to identify the genomic variants found in the region. The approach uses 122 samples from the 13 countries of the Middle East sourced from the Global Initiative on Sharing All Influenza Data (GISAID). Findings We identified 2200 distinct genome variants including 129 downstream gene variants, 298 frame shift variants, 789 missense variants, 1 start lost, 13 start gained, 1 stop lost, 249 synonymous variants and 720 upstream gene variants. The most common, high impact variants were 10818delTinsG, 2772delCinsC, 14159delCinsC and 2789delAinsA. Variant alignment and phylogenetic tree generation indicates that samples from Iran likely introduced COVID-19 to the rest of the Middle East. Interpretation The phylogenetic and variant analysis provides unique insight into mutation types in genomes. Initial introduction of COVID-19 was most likely due to Iranian transmission. Some countries show evidence of novel mutations and unique strains. Increased time in small populations is likely to contribute to more unique genomes. This study provides more in depth analysis of the variants affecting in the region than any other study. Funding None url: https://doi.org/10.1101/2020.10.09.332692 doi: 10.1101/2020.10.09.332692 id: cord-103301-v4l9sovt author: Bloom, David C. title: Immunization by replication-competent controlled herpesvirus vectors date: 2018-04-11 words: 2332.0 sentences: 120.0 pages: flesch: 45.0 cache: ./cache/cord-103301-v4l9sovt.txt txt: ./txt/cord-103301-v4l9sovt.txt summary: We found that localized activation in 8 mice of efficient but limited replication of a replication-competent controlled herpesvirus 9 vector resulted in a greatly enhanced immune response to the virus or an expressed 10 heterologous antigen. We found that localized activation in 8 mice of efficient but limited replication of a replication-competent controlled herpesvirus 9 vector resulted in a greatly enhanced immune response to the virus or an expressed 10 heterologous antigen. HSV-GS7 replication was also tightly controlled in vivo, two of three groups of mice 8 were administered HSV-GS7 virus (50,000 pfu per mouse) to the footpad, and the mice 9 of one of the latter groups were given ulipristal intraperitoneally (i,p.) as well as, 3 h 10 later, were subjected to a heat treatment to the footpads at 45 0 C for 10 min. abstract: Replication-competent controlled virus vectors were derived from virulent HSV-1 wildtype strain 17syn+ by placing one or two replication-essential genes under the stringent control of a gene switch that is co-activated by heat and an antiprogestin. Upon activation of the gene switch, the vectors replicate in infected cells with an efficacy that approaches that of the wildtype virus from which they were derived. Essentially no replication occurs in the absence of activation. When administered to mice, localized application of a transient heat treatment in the presence of systemic antiprogestin results in efficient but limited virus replication at the site of administration. The immunogenicity of these viral vectors was tested in a mouse footpad lethal challenge model. Unactivated viral vectors - which may be regarded as equivalents of inactivated vaccines - induced detectable protection against lethality caused by wildtype virus challenge. Single activation of the viral vectors at the site of administration (rear footpads) greatly enhanced protective immune responses, and second immunization resulted in complete protection. Once activated vectors also induced far better neutralizing antibody and HSV-1-specific T cells responses than unactivated vectors. To find out whether the immunogenicity of a heterologous antigen was also enhanced in the context of efficient transient vector replication, a virus vector constitutively expressing an equine influenza virus hemagglutinin was constructed. Immunization of mice with this recombinant induced detectable antibody-mediated neutralization of equine influenza virus as well as a hemagglutinin-specific T cell response. Single activation of viral replication resulted in a several-fold enhancement of this immune response. IMPORTANCE We hypothesized that vigorous replication of a pathogen may be critical for eliciting the most potent and balanced immune response against it. Hence, attenuation/inactivation (as in conventional vaccines) should be avoided. Instead, necessary safety should be provided by placing replication of the pathogen under stringent control and of activating time-limited replication of the pathogen strictly in an administration region in which pathology cannot develop. Immunization will then occur in the context of highly efficient pathogen replication and uncompromised safety. We found that localized activation in mice of efficient but limited replication of a replication-competent controlled herpesvirus vector resulted in a greatly enhanced immune response to the virus or an expressed heterologous antigen. This finding supports the above hypothesis as well as suggests that the vectors may be promising novel agents worth exploring for the prevention/mitigation of infectious diseases for which efficient vaccination is lacking, in particular in immunocompromised patients. url: https://doi.org/10.1101/299230 doi: 10.1101/299230 id: cord-313910-bwe2f7xf author: Bojadzic, Damir title: Small-Molecule In Vitro Inhibitors of the Coronavirus Spike – ACE2 Protein-Protein Interaction as Blockers of Viral Attachment and Entry for SARS-CoV-2 date: 2020-10-22 words: 7049.0 sentences: 346.0 pages: flesch: 54.0 cache: ./cache/cord-313910-bwe2f7xf.txt txt: ./txt/cord-313910-bwe2f7xf.txt summary: Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel drug-like compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC50s of 0.2-3.0 μM); whereas, control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. We were able to set up a cell-free ELISA-type assay to quantify the binding of SARS-CoV-2 S protein (as well as its SARS-CoV analog) to their cognate receptors (human ACE2) and used this to screen our existing in-house compound library containing a large variety of organic dyes and a set of colorless analogs prepared as potential SMIs for costimulatory PPIs. These maintain the main molecular framework of dyes but lack the aromatic azo chromophores responsible for the color as they are replaced with amide linkers (58, 59). abstract: Inhibitors of the protein-protein interaction (PPI) between the SARS-CoV-2 spike protein and ACE2, which acts as a ligand-receptor pair that initiates the viral attachment and cellular entry of this coronavirus causing the ongoing COVID-19 pandemic, are of considerable interest as potential antiviral agents. While blockade of such PPIs with small molecules is more challenging than with antibodies, small-molecule inhibitors (SMIs) might offer alternatives that are less strain- and mutation-sensitive, suitable for oral or inhaled administration, and more controllable / less immunogenic. Here, we report the identification of SMIs of this PPI by screening our compound-library that is focused on the chemical space of organic dyes. Among promising candidates identified, several dyes (Congo red, direct violet 1, Evans blue) and novel drug-like compounds (DRI-C23041, DRI-C91005) inhibited the interaction of hACE2 with the spike proteins of SARS-CoV-2 as well as SARS-CoV with low micromolar activity in our cell-free ELISA-type assays (IC50s of 0.2-3.0 μM); whereas, control compounds, such as sunset yellow FCF, chloroquine, and suramin, showed no activity. Protein thermal shift assays indicated that the SMIs identified here bind SARS-CoV-2-S and not ACE2. Selected promising compounds inhibited the entry of a SARS-CoV-2-S expressing pseudovirus into ACE2-expressing cells in concentration-dependent manner with low micromolar IC50s (6-30 μM). This provides proof-of-principle evidence for the feasibility of small-molecule inhibition of PPIs critical for coronavirus attachment/entry and serves as a first guide in the search for SMI-based alternative antiviral therapies for the prevention and treatment of diseases caused by coronaviruses in general and COVID-19 in particular. url: https://doi.org/10.1101/2020.10.22.351056 doi: 10.1101/2020.10.22.351056 id: cord-102321-csdezu6y author: Booeshaghi, A. Sina title: Normalization of single-cell RNA-seq counts by log(x+1)* or log(1+x)* date: 2020-10-14 words: 1272.0 sentences: 84.0 pages: flesch: 63.0 cache: ./cache/cord-102321-csdezu6y.txt txt: ./txt/cord-102321-csdezu6y.txt summary: log(1+x) count normalization introduces errors for lowly expressed genes The average log(1+x) expression differs considerably from log(x) when x is small An alternative approach is to use the fraction of cells with non-zero expression As is common in single-cell RNA-seq, the expression estimates of ACE2 are derived from counts that are filtered and normalized. While single-cell RNA-seq expression data has been modeled with many different distributions [4, 5] , for simplicity in illustrating our points we model this count data with a simple Poisson random variable X with parameter λ in order to demonstrate the implications of this restriction. Since f is approximately equal to this expression when f is small, this provides an interpretation of the fraction of cells with at least one copy of a low-abundance gene as an estimate of the rate parameter λ in a Poisson distribution. abstract: Single-cell RNA-seq technologies have been successfully employed over the past decade to generate many high resolution cell atlases. These have proved invaluable in recent efforts aimed at understanding the cell type specificity of host genes involved in SARS-CoV-2 infections. While single-cell atlases are based on well-sampled highly-expressed genes, many of the genes of interest for understanding SARS-CoV-2 can be expressed at very low levels. Common assumptions underlying standard single-cell analyses don’t hold when examining low-expressed genes, with the result that standard workflows can produce misleading results. Key Points Lowly expressed genes in single-cell RNA-seq can be easliy misanalyzed. log(1+x) count normalization introduces errors for lowly expressed genes The average log(1+x) expression differs considerably from log(x) when x is small An alternative approach is to use the fraction of cells with non-zero expression url: https://doi.org/10.1101/2020.05.19.100214 doi: 10.1101/2020.05.19.100214 id: cord-102551-8igfuaw2 author: Boonyaratanakornkit, Jim title: Protective Antibodies Against Human Parainfluenza Virus Type 3 (HPIV3) Infection date: 2020-10-30 words: 8067.0 sentences: 462.0 pages: flesch: 53.0 cache: ./cache/cord-102551-8igfuaw2.txt txt: ./txt/cord-102551-8igfuaw2.txt summary: HPIV3, like respiratory syncytial virus (RSV), infects early in life and frequently causes severe bronchiolitis and pneumonia in infants under six months of age who are unable to mount a robust antibody response 2,3 . HPIV3 F was recently stabilized in the preF conformation and induced higher serum neutralizing titers than the HPIV3 postF To focus upon B cells producing neutralizing antibodies, we modified our assay to sort individual B cells onto irradiated 3T3 feeder cells expressing CD40L, IL-2, and IL-21 to allow for higher throughput screening of culture supernatants for neutralization prior to antibody cloning, as described 27 . Using this approach, we found that 14% of IgD -HPIV3 preF-binding B cells sorted from tonsils produced HPIV3 neutralizing antibodies, as compared to 5% from the spleen and 2% from peripheral blood (Fig. 3b) . abstract: Human parainfluenza virus type III (HPIV3) is a common respiratory pathogen that afflicts children and can be fatal in vulnerable populations, including the immunocompromised. Unfortunately, an effective vaccine or therapeutic is not currently available, resulting in tens of thousands of hospitalizations per year. In an effort to discover a protective antibody against HPIV3, we screened the B cell repertoires from peripheral blood, tonsils, or spleen from healthy children and adults. These analyses yielded five monoclonal antibodies that potently neutralized HPIV3 in vitro. These HPIV3 neutralizing antibodies targeted two non-overlapping epitopes of the HPIV3 F protein, with most targeting the apex. Importantly, prophylactic administration of one of these antibodies, named PI3-E12, resulted in potent protection against HPIV3 infection in cotton rats. Additionally, PI3-E12 could also be used therapeutically to suppress HPIV3 in immunocompromised animals. These results demonstrate the potential clinical utility of PI3-E12 for the prevention or treatment of HPIV3 in both immunocompetent and immunocompromised individuals. url: https://doi.org/10.1101/2020.06.15.153478 doi: 10.1101/2020.06.15.153478 id: cord-271970-i35pic5o author: Boris, Bonaventure title: A genome-wide CRISPR/Cas9 knock-out screen identifies the DEAD box RNA helicase DDX42 as a broad antiviral inhibitor date: 2020-10-28 words: 6320.0 sentences: 343.0 pages: flesch: 52.0 cache: ./cache/cord-271970-i35pic5o.txt txt: ./txt/cord-271970-i35pic5o.txt summary: Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Deep sequencing analysis of the GeCKO cell populations showed more than 94% coverage for both libraries (≥ 10 reads for 61,598 and 54,609 sgRNA-coding sequences out of GeCKO populations were subjected to type 1 IFN treatment in order to induce the antiviral state and, 24h later, incubated with VSV-G-pseudotyped, HIV-1 based LVs coding for an antibiotic resistance cassette. In order to validate the effect of DDX42 KO on HIV-1 infection in another model cell line, two additional sgRNAs were designed (sgRNA-2 and -3) and used in parallel to the one identified in the GeCKO screen (sgDDX42-1) (Figure 2A ). abstract: Genome-wide CRISPR/Cas9 knock-out genetic screens are powerful approaches to unravel new regulators of viral infections. With the aim of identifying new cellular inhibitors of HIV-1, we have developed a strategy in which we took advantage of the ability of type 1 interferon (IFN) to potently inhibit HIV-1 infection, in order to create a cellular environment hostile to viral replication. This approach led to the identification of the DEAD-box RNA helicase DDX42 as an intrinsic inhibitor of HIV-1. Depletion of endogenous DDX42 using siRNA or CRISPR/Cas9 knock-out increased HIV-1 infection, both in model cell lines and in physiological targets of HIV-1, primary CD4+ T cells and monocyte-derived macrophages (MDMs), and irrespectively of the IFN treatment. Similarly, the overexpression of a dominant-negative mutant of DDX42 positively impacted HIV-1 infection, whereas wild-type DDX42 overexpression potently inhibited HIV-1 infection. The positive impact of endogenous DDX42 depletion on HIV-1 infection was directly correlated to an increase in viral DNA accumulation. Interestingly, proximity ligation assays showed that DDX42, which can be mainly found in the nucleus but is also present in the cytoplasm, was in the close vicinity of HIV-1 Capsid during infection of primary monocyte-derived macrophages. Moreover, we show that DDX42 is also able to substantially decrease infection with other retroviruses and retrotransposition of long interspersed elements-1 (LINE-1). Finally, we reveal that DDX42 potently inhibits other pathogenic viruses, including Chikungunya virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). url: https://doi.org/10.1101/2020.10.28.359356 doi: 10.1101/2020.10.28.359356 id: cord-326736-jd6fvaop author: Bosco-Lauth, Angela M. title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats date: 2020-05-29 words: 922.0 sentences: 68.0 pages: flesch: 50.0 cache: ./cache/cord-326736-jd6fvaop.txt txt: ./txt/cord-326736-jd6fvaop.txt summary: title: Pathogenesis, transmission and response to re-exposure of SARS-CoV-2 in domestic cats Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naïve cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. The first report of reverse zoonosis, or transmission from human to animal, was reported 46 from Hong Kong, where a COVID patient''s dog tested PCR positive for SARS2 multiple times 47 (Sit et al. Absence of SARS-CoV-2 infection in cats and dogs in close contact with a cluster of 414 COVID-19 patients in a veterinary campus Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS-coronavirus 2 Transmission of 422 SARS-CoV-2 in Domestic Cats abstract: The pandemic caused by SARS-CoV-2 has reached nearly every country in the world with extraordinary person-to-person transmission. The most likely original source of the virus was spillover from an animal reservoir and subsequent adaptation to humans sometime during the winter of 2019 in Wuhan Province, China. Because of its genetic similarity to SARS-CoV-1, it is likely that this novel virus has a similar host range and receptor specificity. Due to concern for human-pet transmission, we investigated the susceptibility of domestic cats and dogs to infection and potential for infected cats to transmit to naïve cats. We report that cats are highly susceptible to subclinical infection, with a prolonged period of oral and nasal viral shedding that is not accompanied by clinical signs, and are capable of direct contact transmission to other cats. These studies confirm that cats are susceptible to productive SARS-CoV-2 infection, but are unlikely to develop clinical disease. Further, we document that cats develop a robust neutralizing antibody response that prevented re-infection to a second viral challenge. Conversely, we found that dogs do not shed virus following infection, but do mount an anti-viral neutralizing antibody response. There is currently no evidence that cats or dogs play a significant role in human exposure; however, reverse zoonosis is possible if infected owners expose their domestic pets during acute infection. Resistance to re-exposure holds promise that a vaccine strategy may protect cats, and by extension humans, to disease susceptibility. url: https://doi.org/10.1101/2020.05.28.120998 doi: 10.1101/2020.05.28.120998 id: cord-102449-6foh1uvn author: Bosker, Hans Rutger title: Beat gestures influence which speech sounds you hear date: 2020-07-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Beat gestures – spontaneously produced biphasic movements of the hand – are among the most frequently encountered co-speech gestures in human communication. They are closely temporally aligned to the prosodic characteristics of the speech signal, typically occurring on lexically stressed syllables. Despite their prevalence across speakers of the world’s languages, how beat gestures impact spoken word recognition is unclear. Can these simple ‘flicks of the hand’ influence speech perception? Across six experiments, we demonstrate that beat gestures influence the explicit and implicit perception of lexical stress (e.g., distinguishing OBject from obJECT), and in turn, can influence what vowels listeners hear. Thus, we provide converging evidence for a manual McGurk effect: even the simplest ‘flicks of the hands’ influence which speech sounds we hear. SIGNIFICANCE STATEMENT Beat gestures are very common in human face-to-face communication. Yet we know little about their behavioral consequences for spoken language comprehension. We demonstrate that beat gestures influence the explicit and implicit perception of lexical stress, and, in turn, can even shape what vowels we think we hear. This demonstration of a manual McGurk effect provides some of the first empirical support for a recent multimodal, situated psycholinguistic framework of human communication, while challenging current models of spoken word recognition that do not yet incorporate multimodal prosody. Moreover, it has the potential to enrich human-computer interaction and improve multimodal speech recognition systems. url: https://doi.org/10.1101/2020.07.13.200543 doi: 10.1101/2020.07.13.200543 id: cord-336560-m5u6ryy9 author: Boudewijns, Robbert title: STAT2 signaling as double-edged sword restricting viral dissemination but driving severe pneumonia in SARS-CoV-2 infected hamsters date: 2020-07-02 words: 5019.0 sentences: 308.0 pages: flesch: 51.0 cache: ./cache/cord-336560-m5u6ryy9.txt txt: ./txt/cord-336560-m5u6ryy9.txt summary: Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients. The lack of readily accessible serum markers or the absence of overt disease symptoms in hamsters prompted us to establish a non-invasive means to score for lung infection and SARS-CoV-2 induced lung disease by computed tomography (CT) as used in standard patient care to aid COVID-19 diagnosis with high sensitivity and monitor progression/recovery 7, 33, 35, 36 . Similar as in humans 37 , semiquantitative lung pathology scores were obtained from high-resolution chest micro-CT scans of freebreathing animals 38 The increase in replication of SARS-CoV-2 seen in IL28R-a -/hamsters, on one hand, combined with a tempered inflammatory response and lung injury as compared to WT hamsters, on the other hand, is in line with the role of type III IFN plays during respiratory virus infections, including SARS-CoV-1 53 . abstract: Since the emergence of SARS-CoV-2 causing COVID-19, the world is being shaken to its core with numerous hospitalizations and hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that productive SARS-CoV-2 infection in the lungs of mice is limited and restricted by early type I interferon responses. In contrast, we show that Syrian hamsters are highly permissive to SARS- CoV-2 and develop bronchopneumonia and a strong inflammatory response in the lungs with neutrophil infiltration and edema. Moreover, we identify an exuberant innate immune response as a key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Finally, we assess SARS-CoV- 2-induced lung pathology in hamsters by micro-CT alike used in clinical practice. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients. url: https://doi.org/10.1101/2020.04.23.056838 doi: 10.1101/2020.04.23.056838 id: cord-300707-k9uk14b3 author: Bouwman, Kim M. title: Multimerization- and glycosylation-dependent receptor binding of SARS-CoV-2 spike proteins date: 2020-09-04 words: 2328.0 sentences: 176.0 pages: flesch: 59.0 cache: ./cache/cord-300707-k9uk14b3.txt txt: ./txt/cord-300707-k9uk14b3.txt summary: Here we created monomeric and trimeric fluorescent RBD proteins, derived from adherent HEK293T, as well as in GnTI mutant cells, to analyze the effect of complex vs high mannose glycosylation on receptor binding. Our results show that fully glycosylated trimeric RBD proteins are attractive to analyze receptor binding and explore ACE2 expression profiles in tissues. The results demonstrate 104 that fully glycosylated trimeric SARS-CoV-2 RBD proteins reveal the 105 differences in ACE2 expression between cell cultures and tissue sections. A similar trend of binding intensities was observed for 214 monomeric, trimeric, and different N-glycosylated SARS-CoV-RBD proteins 215 fused to mOrange2 ( Fig S3A) . 226 227 To confirm our observations of different binding on tissues, we quantified the 228 intensities of the ACE2 antibody and SARS-CoV-1 and -2 RBD proteins, except 229 for the monomeric GnTI derived proteins as these were almost at the 230 background ( Fig 4D) . abstract: Receptor binding studies using recombinant SARS-CoV proteins have been hampered due to challenges in approaches creating spike protein or domains thereof, that recapitulate receptor binding properties of native viruses. We hypothesized that trimeric RBD proteins would be suitable candidates to study receptor binding properties of SARS-CoV-1 and -2. Here we created monomeric and trimeric fluorescent RBD proteins, derived from adherent HEK293T, as well as in GnTI mutant cells, to analyze the effect of complex vs high mannose glycosylation on receptor binding. The results demonstrate that trimeric fully glycosylated proteins are superior in receptor binding compared to monomeric and immaturely glycosylated variants. Although differences in binding to commonly used cell lines were minimal between the different RBD preparations, substantial differences were observed when respiratory tissues of experimental animals were stained. The RBD trimers demonstrated distinct ACE2 expression profiles in bronchiolar ducts and confirmed the higher binding affinity of SARS-CoV-2 over SARS-CoV-1. Our results show that fully glycosylated trimeric RBD proteins are attractive to analyze receptor binding and explore ACE2 expression profiles in tissues. url: https://doi.org/10.1101/2020.09.04.282558 doi: 10.1101/2020.09.04.282558 id: cord-279474-c5y2lygj author: Bozzo, Caterina Prelli title: IFITM proteins promote SARS-CoV-2 infection of human lung cells date: 2020-08-18 words: 1110.0 sentences: 90.0 pages: flesch: 55.0 cache: ./cache/cord-279474-c5y2lygj.txt txt: ./txt/cord-279474-c5y2lygj.txt summary: Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) restrict numerous viral pathogens and are thought to prevent infection by severe acute respiratory syndrome coronaviruses (SARS-CoVs). In striking contrast, however, endogenous IFITM expression promoted genuine SARS-CoV-2 infection in human lung cells both in the presence and absence of interferon. Taken together, our results show that all three IFITMs prevent SARS-CoV-2 S/ACE2-mediated attachment and membrane fusion in single round pseudotype infection assays. Notably, titration experiments showed that IFITMs do not promote genuine SARS-CoV-2 247 infection in HEK239T cells over a broad range of expression levels ( Figure S4E ). (F) Quantification of the entry of VSV(luc)ΔG*-SARS-CoV-2-S by luciferase activity in HEK293T cells transiently expressing indicated proteins (IFITM mutants) and infected 24 h post-transfection with the VSVpp (MOI 0.025) for 16 h. (G) Quantification of the entry of HIV(Fluc)Δenv*-SARS-CoV-2-S by luciferase activity in HEK293T cells stably expressing indicated proteins (IFITM mutants) and ACE2 abstract: Interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) restrict numerous viral pathogens and are thought to prevent infection by severe acute respiratory syndrome coronaviruses (SARS-CoVs). However, most evidence comes from single-round pseudoparticle infection of cells artificially overexpressing IFITMs. Here, we confirmed that overexpression of IFITMs blocks pseudoparticle infections mediated by the Spike proteins of β-coronaviruses including pandemic SARS-CoV-2. In striking contrast, however, endogenous IFITM expression promoted genuine SARS-CoV-2 infection in human lung cells both in the presence and absence of interferon. IFITM2 was most critical for efficient entry of SARS-CoV-2 and enhanced virus production from Calu-3 cells by several orders of magnitude. IFITMs are expressed and further induced by interferons in the lung representing the primary site of SARS-CoV-2 infection as well as in other relevant tissues. Our finding that IFITMs enhance SARS-CoV-2 infection under conditions approximating the in vivo situation shows that they may promote viral invasion during COVID-19. HIGHLIGHTS Overexpression of IFITM1, 2 and 3 restricts SARS-CoV-2 infection Endogenous IFITM1, 2 and 3 boost SARS-CoV-2 infection of human lung cells IFITM2 is critical for efficient entry of SARS-CoV-2 in Calu-3 cells url: https://doi.org/10.1101/2020.08.18.255935 doi: 10.1101/2020.08.18.255935 id: cord-102530-wetqqt2i author: Brandell, Ellen E. title: The rise of disease ecology date: 2020-07-17 words: 2707.0 sentences: 171.0 pages: flesch: 50.0 cache: ./cache/cord-102530-wetqqt2i.txt txt: ./txt/cord-102530-wetqqt2i.txt summary: The steady increase in topics such as climate change, and emerging infectious diseases, superspreaders indicate that disease ecology as a field of research will continue advancing our understanding of complex host-pathogen interactions and forms a critical and adaptable component of the global response to emergent health and environmental threats. In addition 164 to topics that emerged from the literature, we also generated and assessed our own topic lists based on key research areas, such as climate change, dilution effect, superspreaders, network 166 analysis, EIDs, bovine tuberculosis, infectious diseases in bats and rodents, and chytrid fungus 167 ( Fig. 4) . Using key term searches, we next explored select topic trends: climate change, emerging 293 infectious diseases (EIDs), the dilution effect, superspreaders, network analysis, pathogens in 294 rodents and bats, bovine tuberculosis, and chytrid fungus in amphibians (Fig. 4B) . abstract: Disease ecology is an interdisciplinary field that has recently rapidly grown in size and influence. We described the composition and educational experiences of disease ecology practitioners and identified changes in research foci. We combined a global survey with a literature synthesis involving machine-learning topic detection. Disease ecology practitioners have diversified in the last decade in terms of gender identity and institution, with weaker diversification in terms of race and ethnicity. Topic detection analysis of over 18,500 research articles revealed research foci that have declined (e.g., HIV), increased (e.g., infectious disease in bats), and have remained common (e.g., malaria ecology, influenza). The steady increase in topics such as climate change, and emerging infectious diseases, superspreaders indicate that disease ecology as a field of research will continue advancing our understanding of complex host-pathogen interactions and forms a critical and adaptable component of the global response to emergent health and environmental threats. url: https://doi.org/10.1101/2020.07.16.207100 doi: 10.1101/2020.07.16.207100 id: cord-260793-bb4h255w author: Brann, David H. title: Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia date: 2020-05-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Altered olfactory function is a common symptom of COVID-19, but its etiology is unknown. A key question is whether SARS-CoV-2 (CoV-2) – the causal agent in COVID-19 – affects olfaction directly by infecting olfactory sensory neurons or their targets in the olfactory bulb, or indirectly, through perturbation of supporting cells. Here we identify cell types in the olfactory epithelium and olfactory bulb that express SARS-CoV-2 cell entry molecules. Bulk sequencing revealed that mouse, non-human primate and human olfactory mucosa expresses two key genes involved in CoV-2 entry, ACE2 and TMPRSS2. However, single cell sequencing and immunostaining demonstrated ACE2 expression in support cells, stem cells, and perivascular cells; in contrast, neurons in both the olfactory epithelium and bulb did not express ACE2 message or protein. These findings suggest that CoV-2 infection of non-neuronal cell types leads to anosmia and related disturbances in odor perception in COVID-19 patients. url: https://doi.org/10.1101/2020.03.25.009084 doi: 10.1101/2020.03.25.009084 id: cord-290694-jmav8xi4 author: Bridgland, Victoria M. E. title: Why the COVID-19 pandemic is a traumatic stressor date: 2020-09-22 words: 1102.0 sentences: 68.0 pages: flesch: 57.0 cache: ./cache/cord-290694-jmav8xi4.txt txt: ./txt/cord-290694-jmav8xi4.txt summary: The COVID-19 pandemic does not fit into prevailing Post-traumatic Stress Disorder (PTSD) models, or diagnostic criteria, yet emerging research shows traumatic stress symptoms as a result of this ongoing global stressor. Nevertheless, among a sample of online participants (N = 1,040) in five western countries, we found participants had PTSD-like symptoms for events that had not happened and when participants had been directly (e.g., contact with virus) or indirectly exposed to COVID-19 (e.g., via media). Posttraumatic Stress Disorder Checklist-5 (PCL-5 (22)), adapted to measure pre/peri/post-145 traumatic reactions, and measures of general emotional reactions, well-being, psychosocial 146 functioning, and depression, anxiety, and stress symptoms. We then re-presented the 209 same list of events, but asked participants to select events they were concerned about 210 happening in the future ("other" events led to three additional categories [seven responses The PTSD Checklist (PCL-5 (22)). abstract: The COVID-19 pandemic does not fit into prevailing Post-traumatic Stress Disorder (PTSD) models, or diagnostic criteria, yet emerging research shows traumatic stress symptoms as a result of this ongoing global stressor. Current pathogenic event models focus on past, and largely direct, trauma exposure to certain kinds of life-threatening events. Nevertheless, among a sample of online participants (N = 1,040) in five western countries, we found participants had PTSD-like symptoms for events that had not happened and when participants had been directly (e.g., contact with virus) or indirectly exposed to COVID-19 (e.g., via media). Moreover, 13.2% of our sample were likely PTSD-positive, despite types of COVID-19 “exposure” (e.g., lockdown) not fitting DSM-5 criteria. The emotional impact of “worst” experienced/anticipated events best predicted PTSD-like symptoms. Our findings add to existing literature supporting a pathogenic event memory model of traumatic stress. url: https://doi.org/10.1101/2020.09.22.307637 doi: 10.1101/2020.09.22.307637 id: cord-328189-jpkxjn6e author: Brielle, Esther S. title: The SARS-CoV-2 exerts a distinctive strategy for interacting with the ACE2 human receptor date: 2020-03-12 words: 2971.0 sentences: 172.0 pages: flesch: 53.0 cache: ./cache/cord-328189-jpkxjn6e.txt txt: ./txt/cord-328189-jpkxjn6e.txt summary: We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. Herein, we analyze the binding of several CoV RBDs to ACE2 with molecular dynamics (MD) simulations and compare the stability, relative interaction strength, and dynamics of the interaction between the viral spike protein and the human ACE2 receptor. While the sequence identity between the RBDs of COVID-19 and SARS-2002 is 73% (Table 1) , we observe a significantly higher residue substitution rate at the interaction interface with the ACE2 receptor. Our MD simulation analysis reveals that the SARS-des has a substantially lower interaction scores with ACE2 (median of -2199.2, Fig. S2) , as expected for an optimized human ACE2-binding RBD design. We relied on the crystal structure of the spike protein receptor-binding domain from a SARS coronavirus designed human strain complexed with the human receptor ACE2 (PDB 3SCI, resolution 2.9Å) as a template for comparative modeling. abstract: The COVID-19 disease has plagued over 110 countries and has resulted in over 4,000 deaths within 10 weeks. We compare the interaction between the human ACE2 receptor and the SARS-CoV-2 spike protein with that of other pathogenic coronaviruses using molecular dynamics simulations. SARS-CoV, SARS-CoV-2, and HCoV-NL63 recognize ACE2 as the natural receptor but present a distinct binding interface to ACE2 and a different network of residue-residue contacts. SARS-CoV and SARS-CoV-2 have comparable binding affinities achieved by balancing energetics and dynamics. The SARS-CoV-2–ACE2 complex contains a higher number of contacts, a larger interface area, and decreased interface residue fluctuations relative to SARS-CoV. These findings expose an exceptional evolutionary exploration exerted by coronaviruses toward host recognition. We postulate that the versatility of cell receptor binding strategies has immediate implications on therapeutic strategies. One Sentence Summary Molecular dynamics simulations reveal a temporal dimension of coronaviruses interactions with the host receptor. url: https://doi.org/10.1101/2020.03.10.986398 doi: 10.1101/2020.03.10.986398 id: cord-103511-31njndob author: Broggi, Achille title: Type III interferons disrupt the lung epithelial barrier upon viral recognition date: 2020-05-05 words: 3886.0 sentences: 283.0 pages: flesch: 61.0 cache: ./cache/cord-103511-31njndob.txt txt: ./txt/cord-103511-31njndob.txt summary: Accordingly, sorted lung resident dendritic cells express 192 high levels of IFN-λ transcript after 5 days of poly (I:C) treatment, in contrast to epithelial cells, 193 alveolar macrophages and monocytes (Fig. 4A) , which, instead, express inflammatory cytokines (Fig. S8A, B) . Moreover, diphtheria toxin (DT)-mediated depletion of 195 CD11c + cells in CD11c-DT receptor (DTR) mice was sufficient to completely abolish IFN-λ 9 transcript and protein upregulation upon 6 days of poly (I:C) treatment (Fig. 4B, C) , while production remained unaltered (Fig. S8C with the response measured in vivo, TLR7 stimulation did not induce IFN production while it 207 induced upregulation of pro-inflammatory cytokines, and intracellular delivery of poly (I:C) induced 208 high levels of IFN-I but not IFN-λ (Fig.4D, Fig. S9A , B). Dendritic cells sorted from Ticam1 -/mice treated with poly (I:C) for six 222 days did not express appreciable levels of IFN-λ transcripts while still produced type I interferons 223 ( Fig. 4E, F) . abstract: Lower respiratory tract infections are a leading cause of mortality driven by infectious agents. RNA viruses such as influenza virus, respiratory syncytial virus and the new pandemic coronavirus SARS-CoV-2 can be highly pathogenic. Clinical and experimental evidence indicate that most severe and lethal cases do not depend on the viral burden and are, instead, characterized by an aberrant immune response. In this work we assessed how the innate immune response contributes to the pathogenesis of RNA virus infections. We demonstrate that type III interferons produced by dendritic cells in the lung in response to viral recognition cause barrier damage and compromise the host tissue tolerance. In particular, type III interferons inhibit tissue repair and lung epithelial cell proliferation, causing susceptibility to lethal bacterial superinfections. Overall, our data give a strong mandate to rethink the pathophysiological roles of this group of interferons and their possible use in the clinical practice against endemic as well as emerging viral infections. url: https://doi.org/10.1101/2020.05.05.077867 doi: 10.1101/2020.05.05.077867 id: cord-312038-g76cpjp7 author: Brunaugh, Ashlee D. title: Broad-Spectrum, Patient-Adaptable Inhaled Niclosamide-Lysozyme Particles are Efficacious Against Coronaviruses in Lethal Murine Infection Models date: 2020-10-07 words: 11043.0 sentences: 517.0 pages: flesch: 47.0 cache: ./cache/cord-312038-g76cpjp7.txt txt: ./txt/cord-312038-g76cpjp7.txt summary: Utilizing repurposed NIC, and with the goal of developing a therapeutically effective, rapidly scalable and globally distributable antiviral therapy to reduce the spread of SARS-CoV-2, we describe an inhalable NIC formulation that can be administered using three major models or respiratory tract delivery systems: DPI, nasal spray and nebulizer. At the highest dose tested (0.125 µg/mL NIC), Vero cells with an established MERS-CoV infection exhibited an 82.2% ± 0.8% decrease in viral load compared to untreated controls after 24-hours of exposure to NIC-hLYS particles ( Fig 1D) . While brain viral titres did not exhibit further reduction from levels noted in the preliminary efficacy study, the inoculation of Vero E6 cells with viral particles obtained from lung and brain homogenates of surviving animals resulted in no observation of CPE at any of the inoculum concentrations tested, which indicates that remaining viral particles were not active. abstract: Niclosamide (NIC) has demonstrated promising in vitro antiviral efficacy against SARS-CoV-2, the causative agent of the COVID-19 pandemic. Though NIC is already FDA-approved, the oral formulation produces systemic drug levels that are too low to inhibit SARS-CoV-2. As an alternative, direct delivery of NIC to the respiratory tract as an aerosol could target the primary site of for SARS-CoV-2 acquisition and spread. We have developed a niclosamide powder suitable for delivery via dry powder inhaler, nebulizer, and nasal spray through the incorporation of human lysozyme (hLYS) as a carrier molecule. This novel formulation exhibits potent in vitro and in vivo activity against MERS-CoV and SARS-CoV-2 and may protect against methicillin-resistance staphylococcus aureus pneumonia and inflammatory lung damage occurring secondary to CoV infections. The suitability of the formulation for all stages of the disease and low-cost development approach will ensure wide-spread utilization url: https://doi.org/10.1101/2020.09.24.310490 doi: 10.1101/2020.09.24.310490 id: cord-298716-pubhq564 author: Bryche, Bertrand title: Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters date: 2020-06-16 words: 3558.0 sentences: 212.0 pages: flesch: 56.0 cache: ./cache/cord-298716-pubhq564.txt txt: ./txt/cord-298716-pubhq564.txt summary: title: Massive transient damage of the olfactory epithelium associated with infection of sustentacular cells by SARS-CoV-2 in golden Syrian hamsters Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria. We measured the OE thickness, the OSN cilia quality (based on Golf staining) and the immune cell infiltration of the olfactory mucosa (based on the Iba1 staining) on 6 images per animal taken from 3 different slides spread along the nasal cavity. Two recent reports indicate that olfactory neurons in hamster (Sia et al., 2020) and respiratory cells in ferret (Ryan et al., 2020) may be the target of SARS-CoV-2 but these studies did not focus on the nasal cavity and they did not use double staining to clearly identify the infected cells in the OE. abstract: Anosmia is one of the most prevalent symptoms of SARS-CoV-2 infection during the COVID-19 pandemic. However, the cellular mechanism behind the sudden loss of smell has not yet been investigated. The initial step of odour detection takes place in the pseudostratified olfactory epithelium (OE) mainly composed of olfactory sensory neurons surrounded by supporting cells known as sustentacular cells. The olfactory neurons project their axons to the olfactory bulb in the central nervous system offering a potential pathway for pathogens to enter the central nervous system by bypassing the blood brain barrier. In the present study, we explored the impact of SARS-COV-2 infection on the olfactory system in golden Syrian hamsters. We observed massive damage of the OE as early as 2 days post nasal instillation of SARS-CoV-2, resulting in a major loss of cilia necessary for odour detection. These damages were associated with infection of a large proportion of sustentacular cells but not of olfactory neurons, and we did not detect any presence of the virus in the olfactory bulbs. We observed massive infiltration of immune cells in the OE and lamina propria of infected animals, which may contribute to the desquamation of the OE. The OE was partially restored 14 days post infection. Anosmia observed in COVID-19 patient is therefore likely to be linked to a massive and fast desquamation of the OE following sustentacular cells infection with SARS-CoV-2 and subsequent recruitment of immune cells in the OE and lamina propria. url: https://doi.org/10.1101/2020.06.16.151704 doi: 10.1101/2020.06.16.151704 id: cord-325432-geb4esu5 author: Bukreyeva, Natalya title: The IMPDH inhibitor merimepodib suppresses SARS-CoV-2 replication in vitro date: 2020-04-09 words: 1036.0 sentences: 65.0 pages: flesch: 49.0 cache: ./cache/cord-325432-geb4esu5.txt txt: ./txt/cord-325432-geb4esu5.txt summary: Drugs with history of being tested in human patients or used for treatment of other conditions offer the most expedient option, and several such drugs are currently being tested for efficacy against SARS-CoV-2, including many broad-spectrum antivirals. One such antiviral, merimepodib (MMPD), has already being tested against hepatitis C in patients as well as against many emerging RNA viruses in cell culture, including Zika, Ebola, Lassa, Junin, and chikungunya viruses (1) . Early work suggests that IMPDH may directly interact with SARS-CoV-2 nsp13, perhaps indicating that drugs targeting IMPDH such as MMPD might have an impact on viral replication (5) . Our results show that MMPD can inhibit SARS-CoV-2 replication at low concentrations. Further work is needed to characterize the full mechanism behind MMPD inhibition of SARS-CoV-2 as well as its efficacy in animal models of corona virus infections. Merimepodib, an IMPDH inhibitor, suppresses replication of Zika virus and other emerging viral pathogens abstract: The ongoing COVID-19 pandemic continues to pose a major public health burden around the world. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected over one million people worldwide as of April, 2020, and has led to the deaths of nearly 300,000 people. No approved vaccines or treatments in the USA currently exist for COVID-19, so there is an urgent need to develop effective countermeasures. The IMPDH inhibitor merimepodib (MMPD) is an investigational antiviral drug that acts as a noncompetitive inhibitor of IMPDH. It has been demonstrated to suppress replication of a variety of emerging RNA viruses. We report here that MMPD suppresses SARS-CoV-2 replication in vitro. After overnight pretreatment of Vero cells with 10 μM of MMPD, viral titers were reduced by 4 logs of magnitude, while pretreatment for 4 hours resulted in a 3-log drop. The effect is dose-dependent, and concentrations as low as 3.3 μM significantly reduced viral titers when the cells were pretreated prior to infection. The results of this study provide evidence that MMPD may be a viable treatment option for COVID-19. url: https://doi.org/10.1101/2020.04.07.028589 doi: 10.1101/2020.04.07.028589 id: cord-102918-bkyk7or9 author: Burns, C. Sean title: Methodological Issues with Search in MEDLINE: A Longitudinal Query Analysis date: 2020-05-22 words: 1414.0 sentences: 89.0 pages: flesch: 51.0 cache: ./cache/cord-102918-bkyk7or9.txt txt: ./txt/cord-102918-bkyk7or9.txt summary: This study compares the results of data collected from a longitudinal query analysis of the MEDLINE database hosted on multiple platforms that include PubMed, EBSCOHost, Ovid, ProQuest, and Web of Science in order to identify variations among the search results on the platforms after controlling for search query syntax. The variation is due to trends in scholarly publication that include publishing online first versus publishing in journal issues, which leads to metadata differences in the bibliographic record; to differences in the level of specificity among search fields provided by the platforms; to database integrity issues that lead to large fluctuations in monthly search results based on the same query; and to database currency issues that arise due to when each platform updates its MEDLINE file. Specific bibliographic databases, like PubMed and MEDLINE, are used to inform clinical decision-making, create systematic reviews, and construct knowledge bases for clinical decision support systems. Comparing the coverage, recall, and precision of searches for 120 systematic reviews in Embase, MEDLINE, and Google Scholar: a prospective study abstract: This study compares the results of data collected from a longitudinal query analysis of the MEDLINE database hosted on multiple platforms that include PubMed, EBSCOHost, Ovid, ProQuest, and Web of Science in order to identify variations among the search results on the platforms after controlling for search query syntax. We devised twenty-nine sets of search queries comprised of five queries per set to search against the five MEDLINE database platforms. We ran our queries monthly for a year and collected search result count data to observe changes. We found that search results vary considerably depending on MEDLINE platform, both within sets and across time. The variation is due to trends in scholarly publication that include publishing online first versus publishing in journal issues, which leads to metadata differences in the bibliographic record; to differences in the level of specificity among search fields provided by the platforms; to database integrity issues that lead to large fluctuations in monthly search results based on the same query; and to database currency issues that arise due to when each platform updates its MEDLINE file. Specific bibliographic databases, like PubMed and MEDLINE, are used to inform clinical decision-making, create systematic reviews, and construct knowledge bases for clinical decision support systems. Since they serve as essential information retrieval and discovery tools that help identify and collect research data and are used in a broad range of fields and as the basis of multiple research designs, this study should help clinicians, researcher, librarians, informationalists, and others understand how these platforms differ and inform future work in their standardization. url: https://doi.org/10.1101/2020.05.22.110403 doi: 10.1101/2020.05.22.110403 id: cord-287372-ya5uvoki author: Böszörményi, Kinga P. title: Comparison of SARS-CoV-2 infection in two non-human primate species: rhesus and cynomolgus macaques date: 2020-11-05 words: 3973.0 sentences: 249.0 pages: flesch: 58.0 cache: ./cache/cord-287372-ya5uvoki.txt txt: ./txt/cord-287372-ya5uvoki.txt summary: This study provides a detailed description of the pathogenesis of a low-passage SARS-CoV-2 isolate in two macaque models and suggests that both species represent an equally good model in research for both COVID-19 prophylactic and therapeutic treatments. Rhesus macaques have also been applied 116 in COVID-19 pathogenesis studies [22, 24, 32, 33] , and to test the efficacy of remdesivir in the 117 treatment of SARS-CoV-2 infection [34] . we compared SARS-CoV-2 replication in rhesus and cynomolgus macaque species and 129 monitored signs of COVID-19-like disease symptoms for three weeks after infection. The animals from this study were not 342 euthanized to be able to perform re-infection studies or to monitor them for late clinical signs, 343 or co-morbidities related to We conclude that the course of SARS-CoV-2 infection of both macaque species is highly 345 similar, indicating that they are equally suitable models to test vaccines and antivirals in a 346 preclinical setting for safety and efficacy. abstract: SARS-CoV-2 is a coronavirus that sparked the current COVID-19 pandemic. To stop the shattering effect of COVID-19, effective and safe vaccines, and antiviral therapies are urgently needed. To facilitate the preclinical evaluation of intervention approaches, relevant animal models need to be developed and validated. Rhesus macaques (Macaca mulatta) and cynomolgus macaques (Macaca fascicularis) are widely used in biomedical research and serve as models for SARS-CoV-2 infection. However, differences in study design make it difficult to compare and understand potential species-related differences. Here, we directly compared the course of SARS-CoV-2 infection in the two genetically closely-related macaque species. After inoculation with a low passage SARS-CoV-2 isolate, clinical, virological, and immunological characteristics were monitored. Both species showed slightly elevated body temperatures in the first days after exposure while a decrease in physical activity was only observed in the rhesus macaques and not in cynomolgus macaques. The virus was quantified in tracheal, nasal, and anal swabs, and in blood samples by qRT-PCR, and showed high similarity between the two species. Immunoglobulins were detected by various enzyme-linked immunosorbent assays (ELISAs) and showed seroconversion in all animals by day 10 post-infection. The cytokine responses were highly comparable between species and computed tomography (CT) imaging revealed pulmonary lesions in all animals. Consequently, we concluded that both rhesus and cynomolgus macaques represent valid models for evaluation of COVID-19 vaccine and antiviral candidates in a preclinical setting. Author summary SARS-CoV-2 infection can have a wide range of symptoms. It can cause asymptomatic or mild disease, but can also have a severe, potentially deadly outcome. Vaccines and antivirals will therefore be crucial in fighting the current COVID-19 pandemic. For testing these prophylactic and therapeutic treatments, and investigating the progression of infection and disease development, animal models play an essential role. In this study, we compare the course of SARS-CoV-2 infection in rhesus and cynomolgus macaques. Both species showed moderate disease symptoms as shown by pulmonary lesions by CT imaging. Shedding of infectious virus from the respiratory system was also documented. This study provides a detailed description of the pathogenesis of a low-passage SARS-CoV-2 isolate in two macaque models and suggests that both species represent an equally good model in research for both COVID-19 prophylactic and therapeutic treatments. url: https://doi.org/10.1101/2020.11.05.369413 doi: 10.1101/2020.11.05.369413 id: cord-102916-t2lcd300 author: Cai, Guoshuai title: SCANNER: A Web Resource for Annotation, Visualization and Sharing of Single Cell RNA-seq Data date: 2020-07-14 words: 1487.0 sentences: 81.0 pages: flesch: 47.0 cache: ./cache/cord-102916-t2lcd300.txt txt: ./txt/cord-102916-t2lcd300.txt summary: title: SCANNER: A Web Resource for Annotation, Visualization and Sharing of Single Cell RNA-seq Data Also, it is equipped with multiple data interfaces for easy data sharing and currently provide a database for studying the smoking effect on single cell gene expression in lung. Contact GCAI@mailbox.sc.edu or XIAOF@mailbox.sc.ecu Key Points SCANNER provides a new web server resource for promoting scRNA-seq data analysis SCANNER enables comprehensive and dynamic analysis and visualization, novel functional annotation and activeness inference, online databases and easy data sharing. In this study, we developed the Single Cell Transcriptomics Annotated Viewer (SCANNER), as a public web resource for scRNA-seq data management, analysis and interpretation in a comprehensive, flexible and collaborative manner. Exploring our database of smoking lung, we found that the gene of the SARS-CoV-2 receptor, ACE2, is mainly expressed in pneumocytes, secretory cells and ciliated cells (Fig. S6) , which is consistent with the recent study of Ziegler et al. abstract: Motivation In recent years, efficient scRNA-seq methods have been developed, enabling the transcriptome profiling of single cells massively in parallel. Meanwhile, its high dimensionality brought challenges in data modeling, analysis, visualization and interpretation. Available analysis tools require extensive knowledge and training of data properties, statistical modeling and computational skills. It is challenging for biologists to efficiently view, browse and interpret the data. Results Here we developed SCANNER, as a public webserver resource to equip the biologists and bioinformatician to share and analyze scRNA-seq data in a comprehensive and collaborative manner. It is effort-less and host-free without requirement on software setup or coding skills, and enables a user-friendly way to compare the activation status of gene sets on single cell basis. Also, it is equipped with multiple data interfaces for easy data sharing and currently provide a database for studying the smoking effect on single cell gene expression in lung. Using SCANNER, we have identified larger proportions of cancer-associated fibroblasts cells and activeness of fibroblast growth related genes in melanoma tissues in females compared to males. Moreover, we found ACE2 is mainly expressed in pneumocytes, secretory cells and ciliated cells with disparity in gene expression by smoking behavior. Availability and implementation SCANNER is available at https://www.thecailab.com/scanner/. Supplementary information Supplementary data are available online. Contact GCAI@mailbox.sc.edu or XIAOF@mailbox.sc.ecu Key Points SCANNER provides a new web server resource for promoting scRNA-seq data analysis SCANNER enables comprehensive and dynamic analysis and visualization, novel functional annotation and activeness inference, online databases and easy data sharing. SCANNER bridges the data analysis and the biological experiment units. url: https://doi.org/10.1101/2020.01.25.919712 doi: 10.1101/2020.01.25.919712 id: cord-295257-iguhy1z8 author: Calcagnile, Matteo title: ACE2 polymorphisms and individual susceptibility to SARS-CoV-2 infection: insights from an in silico study date: 2020-04-24 words: 4785.0 sentences: 253.0 pages: flesch: 49.0 cache: ./cache/cord-295257-iguhy1z8.txt txt: ./txt/cord-295257-iguhy1z8.txt summary: SARS-CoV-2 and respiratory syndrome corona virus (SARS-CoV) Spike proteins share very high phylogenetic similarities (99%), and, indeed, both viruses exploit the same human cell receptor namely angiotensin-converting enzyme 2 (ACE2), a transmembrane enzyme whose expression dominates on lung alveolar epithelial cells 6, 15, 16 . In this study we have used a combination of in silico tools to analyze the possible impact of ACE2 single-nucleotide polymorphisms (SNPs) on the interaction with SARS-CoV-2 Spike glycoprotein. Results indicate that some residues of the ACE2 interface, which are involved in the interaction with SARS-CoV-2 Spike glycoprotein can actually fluctuate (Fig. 5cd ). Indeed, in the rodent blockade of the renin-angiotensin-aldosterone system limits the acute lung injury induced by the SARS-CoV-1 spike protein 49 , suggesting that if ACE2 function is preserved (because of increased baseline expression, as especially seen in pre-menopausal women), clinical course of infection might be less severe. abstract: The current SARS covid-19 epidemic spread appears to be influenced by ethnical, geographical and sex-related factors that may involve genetic susceptibility to diseases. Similar to SARS-CoV, SARS-CoV-2 exploits angiotensin-converting enzyme 2 (ACE2) as a receptor to invade cells, notably type II alveolar epithelial cells. Importantly, ACE2 gene is highly polymorphic. Here we have used in silico tools to analyze the possible impact of ACE2 single-nucleotide polymorphisms (SNPs) on the interaction with SARS-CoV-2 spike glycoprotein. We found that S19P (common in African people) and K26R (common in European people) were, among the most diffused SNPs worldwide, the only two SNPs that were able to potentially affect the interaction of ACE2 with SARS-CoV-2 spike. FireDock simulations demonstrated that while S19P may decrease, K26R might increase the ACE2 affinity for SARS-CoV-2 Spike. This finding suggests that the S19P may genetically protect, and K26R may predispose to more severe SARS-CoV-2 disease. url: https://doi.org/10.1101/2020.04.23.057042 doi: 10.1101/2020.04.23.057042 id: cord-270049-54t3w94z author: Campione, Elena title: Pleiotropic effect of Lactoferrin in the prevention and treatment of COVID-19 infection: randomized clinical trial, in vitro and in silico preliminary evidences date: 2020-08-17 words: 2029.0 sentences: 113.0 pages: flesch: 53.0 cache: ./cache/cord-270049-54t3w94z.txt txt: ./txt/cord-270049-54t3w94z.txt summary: We performed a randomized, prospective, interventional study assessing the role of oral and intra-nasal lactoferrin to treat mild-to-moderate and asymptomatic COVID-19 patients to prevent disease evolution. The antiviral activity of lactoferrin related to its binding to SARS-CoV-2 and cells and protein-protein docking methods, provided the direct recognition between lactoferrin and spike S, thus hindering the spike S attachment to the human ACE2 receptor and consequently virus entering into the cells. 222 We performed the same analysis over the evaluated human lactoferrin (hLF)-Spike complex, 223 obtaining a binding pose superimposable to that observed for the bovine protein (Fig. 5B) . Clinical trial 397 We performed a randomized, prospective, interventional study to assess the efficacy of a liposomal Blood parameters obtained at T0 in COVID-19 group and control group were compared using t-test. abstract: The current treatments against SARS-CoV-2 have proved so far inadequate. A potent antiviral drug is yet to be discovered. Lactoferrin, a multifunctional glycoprotein, secreted by exocrine glands and neutrophils, possesses an antiviral activity extendable to SARS-Cov-2. We performed a randomized, prospective, interventional study assessing the role of oral and intra-nasal lactoferrin to treat mild-to-moderate and asymptomatic COVID-19 patients to prevent disease evolution. Lactoferrin induced an early viral clearance and a fast clinical symptoms recovery in addition to a statistically significant reduction of D-Dimer, Interleukin-6 and ferritin blood levels. The antiviral activity of lactoferrin related to its binding to SARS-CoV-2 and cells and protein-protein docking methods, provided the direct recognition between lactoferrin and spike S, thus hindering the spike S attachment to the human ACE2 receptor and consequently virus entering into the cells. Lactoferrin can be used as a safe and efficacious natural agent to prevent and treat COVID-19 infection. url: https://doi.org/10.1101/2020.08.11.244996 doi: 10.1101/2020.08.11.244996 id: cord-273613-cpiveo7j author: Cao, Xia title: Discovery and Development of Human SARS-CoV-2 Neutralizing Antibodies using an Unbiased Phage Display Library Approach date: 2020-09-29 words: 3505.0 sentences: 178.0 pages: flesch: 46.0 cache: ./cache/cord-273613-cpiveo7j.txt txt: ./txt/cord-273613-cpiveo7j.txt summary: Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Affinity maturation of STI-1499 resulted in identification of STI-2020, an antibody with a 35-fold increased affinity for the SARS-CoV-2 Spike receptor-binding domain (RBD) leading to a greater than 50-fold increase in virus neutralization potency against live WA-1/2020 and 2020001 viruses in vitro. In this study, we detail the initial discovery and profiling of a SARS-CoV-2 nAb isolated from a phage display antibody library derived from the B-cell repertoire of over 600 healthy normal individuals. Candidate nAbs were characterized for binding of Spike S1 subunit and neutralization of related clinical SARS-CoV-2 isolates. abstract: SARS-CoV-2 neutralizing antibodies represent an important component of the ongoing search for effective treatment of and protection against COVID-19. We report here on the use of a naïve phage display antibody library to identify a panel of fully human SARS-CoV-2 neutralizing antibodies. Following functional profiling in vitro against an early pandemic isolate as well as a recently emerged isolate bearing the D614G Spike mutation, the clinical candidate antibody, STI-1499, and the affinity-engineered variant, STI-2020, were evaluated for in vivo efficacy in the Syrian golden hamster model of COVID-19. Both antibodies demonstrated potent protection against the pathogenic effects of the disease and a dose-dependent reduction of virus load in the lungs, reaching undetectable levels following a single dose of 500 micrograms of STI-2020. These data support continued development of these antibodies as therapeutics against COVID-19 and future use of this approach to address novel emerging pandemic disease threats. url: https://doi.org/10.1101/2020.09.27.316174 doi: 10.1101/2020.09.27.316174 id: cord-272986-ebgusf3o author: Cao, Yipeng title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel date: 2020-05-17 words: 4339.0 sentences: 267.0 pages: flesch: 56.0 cache: ./cache/cord-272986-ebgusf3o.txt txt: ./txt/cord-272986-ebgusf3o.txt summary: title: Computational Study of Ions and Water Permeation and Transportation Mechanisms of the SARS-CoV-2 Pentameric E Protein Channel (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel. We tried to use potential mean force (PMF) to reveal the permeability of different physiological ions and water molecules in the pores of the E protein pentamer. Figure 3A shows the PMF of ions and water molecules permeating through the SARS-CoV-2 E protein pentamer pore. The free energy calculation of the ions permeating through the SARS-CoV-2 pentameric E protein channel strongly suggests that the pore has selection permeability for monovalent ions. abstract: Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus (SARS-CoV-2) and represents the causative agent of a potentially fatal disease that is of public health emergency of international concern. Coronaviruses, including SARS-CoV-2, encode an envelope (E) protein, which is a small, hydrophobic membrane protein; the E protein of SARS-CoV-2 has high homology with that of severe acute respiratory syndrome coronavirus. (SARS-CoV) In this study, we provide insights into the function of the SARS-CoV-2 E protein channel and the ion and water permeation mechanisms on the basis of combined in silico methods. Our results suggest that the pentameric E protein promotes the penetration of monovalent ions through the channel. Analysis of the potential mean force (PMF), pore radius and diffusion coefficient reveals that Leu10 and Phe19 are the hydrophobic gates of the channel. In addition, the pore demonstrated a clear wetting/dewetting transition with monovalent cation selectivity under transmembrane voltage, which indicates that it is a hydrophobic voltage-dependent channel. Overall, these results provide structural-basis insights and molecular-dynamic information that are needed to understand the regulatory mechanisms of ion permeability in the pentameric SARS-CoV-2 E protein channel. url: https://doi.org/10.1101/2020.05.17.099143 doi: 10.1101/2020.05.17.099143 id: cord-102178-ju826pao author: Carey, Clayton M. title: Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis date: 2020-03-30 words: 5255.0 sentences: 240.0 pages: flesch: 46.0 cache: ./cache/cord-102178-ju826pao.txt txt: ./txt/cord-102178-ju826pao.txt summary: Under normal conditions, GC-C interacts with endogenous guanylin peptides to promote water secretion in the intestine, but signaling can be hijacked by bacterially-encoded heat-stable enterotoxins (STa) during infection, which leads to overstimulation of GC-C and diarrhea. Phylogenetic analysis in mammals revealed evidence of recurrent positive selection in the GC-C ligand-binding domain in primates and bats, consistent with selective pressures to evade interactions with STa. Using in vitro assays and transgenic intestinal organoids to model STa-mediated diarrhea, we show that GC-C diversification in these lineages results in substantial variation in toxin susceptibility. Under normal conditions, GC-C activity is stimulated by interactions with the endogenous peptides guanylin and uroguanylin, leading to an increase in intracellular cGMP levels in enterocytes lining the small intestine and colon 3 ( Figure 1A ). To test if rapid evolution of GC-C ligand-binding domains result in functional differences in STa susceptibility, we generated cell lines stably expressing GC-C from seven primate and five bat species. abstract: The pathogenesis of infectious diarrheal diseases is largely attributed to enterotoxin proteins that disrupt intestinal water absorption, causing severe dehydration. Despite profound health consequences, the impacts of diarrhea-causing microbes on the evolutionary history of host species are largely unknown. We investigated patterns of genetic variation in mammalian Guanylate Cyclase-C (GC-C), an intestinal receptor frequently targeted by bacterial enterotoxins, to determine how hosts might adapt in response to diarrheal infections. Under normal conditions, GC-C interacts with endogenous guanylin peptides to promote water secretion in the intestine, but signaling can be hijacked by bacterially-encoded heat-stable enterotoxins (STa) during infection, which leads to overstimulation of GC-C and diarrhea. Phylogenetic analysis in mammals revealed evidence of recurrent positive selection in the GC-C ligand-binding domain in primates and bats, consistent with selective pressures to evade interactions with STa. Using in vitro assays and transgenic intestinal organoids to model STa-mediated diarrhea, we show that GC-C diversification in these lineages results in substantial variation in toxin susceptibility. In bats, we observe a unique pattern of compensatory coevolution in the endogenous GC-C ligand uroguanylin, reflecting intense bouts of positive selection at the receptor-ligand interface. These findings demonstrate control of water physiology as a previously unrecognized interface for genetic conflict and reveal diarrheal pathogens as a source of selective pressure among diverse mammals. url: https://doi.org/10.1101/2020.03.29.014761 doi: 10.1101/2020.03.29.014761 id: cord-103460-5thh6syt author: Carlson, Colin J. title: Climate change will drive novel cross-species viral transmission date: 2020-07-14 words: 1438.0 sentences: 74.0 pages: flesch: 52.0 cache: ./cache/cord-103460-5thh6syt.txt txt: ./txt/cord-103460-5thh6syt.txt summary: In addition, changing climate and land use are already driving geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species4,5. Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of geographic range shifts for 3,870 mammal species under climate change and land use scenarios for the year 2070. Range-shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, driving the cross-species transmission of novel viruses at least 4,000 times. Even with dispersal limits, these first encounters are predicted to produce al-207 most one hundred new viral sharing events (RCP 2.6: 96 ± 2.3; RCP 8.5: 86 ± 3.9) that might 208 include ZEBOV, and which cover a much broader part of Africa than the current zoonotic niche 209 of Ebola 68 . abstract: At least 10,000 species of mammal virus are estimated to have the potential to spread in human populations, but the vast majority are currently circulating in wildlife, largely undescribed and undetected by disease outbreak surveillance1,2,3. In addition, changing climate and land use are already driving geographic range shifts in wildlife, producing novel species assemblages and opportunities for viral sharing between previously isolated species4,5. In some cases, this will inevitably facilitate spillover into humans6,7—a possible mechanistic link between global environmental change and emerging zoonotic disease8. Here, we map potential hotspots of viral sharing, using a phylogeographic model of the mammal-virus network, and projections of geographic range shifts for 3,870 mammal species under climate change and land use scenarios for the year 2070. Range-shifting mammal species are predicted to aggregate at high elevations, in biodiversity hotspots, and in areas of high human population density in Asia and Africa, driving the cross-species transmission of novel viruses at least 4,000 times. Counter to expectations, holding warming under 2°C within the century does not reduce new viral sharing, due to greater range expansions—highlighting the need to invest in surveillance even in a low-warming future. Most projected viral sharing is driven by diverse hyperreservoirs (rodents and bats) and large-bodied predators (carnivores). Because of their unique dispersal capacity, bats account for the majority of novel viral sharing, and are likely to share viruses along evolutionary pathways that could facilitate future emergence in humans. Our findings highlight the urgent need to pair viral surveillance and discovery efforts with biodiversity surveys tracking range shifts, especially in tropical countries that harbor the most emerging zoonoses. url: https://doi.org/10.1101/2020.01.24.918755 doi: 10.1101/2020.01.24.918755 id: cord-324892-mg2dziuw author: Carneiro, João title: CoV2ID: Detection and Therapeutics Oligo Database for SARS-CoV-2 date: 2020-06-12 words: 901.0 sentences: 76.0 pages: flesch: 48.0 cache: ./cache/cord-324892-mg2dziuw.txt txt: ./txt/cord-324892-mg2dziuw.txt summary: The first SARS-CoV-2 genomic sequences already showed novel mutations, which may affect the efficiency of available screening tests leading to false-negative diagnosis or inefficient therapeutics. Here we describe the CoV2ID (http://covid.portugene.com/), a free database built to facilitate the evaluation of molecular methods for detection of SARS-CoV-2 and treatment of COVID-19. The database evaluates the available oligonucleotide sequences (PCR primers, RT-qPCR probes, etc.) considering the genetic diversity of the virus. Evaluation of a quantitative RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high throughput system Development of a Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2 Rapid and visual detection of 2019 novel coronavirus (SARS-CoV-2) by a reverse transcription loop-mediated isothermal amplification assay Development of a Novel, Genome Subtraction-Derived, SARS-CoV-2-Specific COVID-19-nsp2 Real-Time RT-PCR Assay and Its Evaluation Using Clinical Specimens abstract: The ability to detect the SARS-CoV-2 in a widespread epidemic is crucial for screening of carriers and for the success of quarantine efforts. Methods based on real-time reverse transcription polymerase chain reaction (RT-qPCR) and sequencing are being used for virus detection and characterization. However, RNA viruses are known for their high genetic diversity which poses a challenge for the design of efficient nucleic acid-based assays. The first SARS-CoV-2 genomic sequences already showed novel mutations, which may affect the efficiency of available screening tests leading to false-negative diagnosis or inefficient therapeutics. Here we describe the CoV2ID (http://covid.portugene.com/), a free database built to facilitate the evaluation of molecular methods for detection of SARS-CoV-2 and treatment of COVID-19. The database evaluates the available oligonucleotide sequences (PCR primers, RT-qPCR probes, etc.) considering the genetic diversity of the virus. Updated sequences alignments are used to constantly verify the theoretical efficiency of available testing methods. Detailed information on available detection protocols are also available to help laboratories implementing SARS-CoV-2 testing. url: https://doi.org/10.1101/2020.04.19.048991 doi: 10.1101/2020.04.19.048991 id: cord-103271-l9n27ocf author: Carozza, Jacqueline A title: Structure-aided development of small molecule inhibitors of ENPP1, the extracellular phosphodiesterase of the immunotransmitter cGAMP date: 2020-05-31 words: 5664.0 sentences: 329.0 pages: flesch: 51.0 cache: ./cache/cord-103271-l9n27ocf.txt txt: ./txt/cord-103271-l9n27ocf.txt summary: Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. Inspired by the molecular scaffold of a previous inhibitor, QS1, 26, 28 which lacks potency at physiological conditions, we build structure-activity relationships (SAR) around the three sections of the molecule -the zinc-binding head, the core, and the tail -and develop several inhibitors with nanomolar Ki values. Assays used to assess the potency of previously attempted ENPP1 inhibitors are inconsistent 26-34 ; however, developing an appropriate assay is key to determining the utility of the molecules in inhibiting cGAMP degradation under physiological conditions. Since our crystal structure suggests that the zinc-binding phosphonate head and quinazoline tail form the most important interactions with ENPP1, we next sought to explore the core region to achieve optimal geometry between these two functional groups ( Fig. 4a-b) . abstract: Cancer cells initiate an innate immune response by synthesizing and exporting the small molecule immunotransmitter cGAMP, which activates the anti-cancer Stimulator of Interferon Genes (STING) pathway in the host. An extracellular enzyme, ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1), hydrolyzes cGAMP and negatively regulates this anti-cancer immune response. Small molecule ENPP1 inhibitors are much needed as tools to study basic biology of extracellular cGAMP and as investigational cancer immunotherapy drugs. Here, we surveyed structure-activity relationships around a series of cell-impermeable and thus extracellular-targeting phosphonate inhibitors of ENPP1. Additionally, we solved the crystal structure of an exemplary phosphonate inhibitor to elucidate the interactions that drive potency. This study yielded several best-in-class compounds with Ki < 2 nM and excellent physicochemical and pharmacokinetic properties. Finally, we demonstrate that an ENPP1 inhibitor delays tumor growth in a breast cancer mouse model. Together, we have developed ENPP1 inhibitors that are excellent tool compounds and potential therapeutics. url: https://doi.org/10.1101/2020.05.30.125534 doi: 10.1101/2020.05.30.125534 id: cord-355397-y69bk5jc author: Caruso, Ícaro P. title: Dynamics of the N-terminal domain of SARS-CoV-2 nucleocapsid protein drives dsRNA melting in a counterintuitive tweezer-like mechanism date: 2020-09-06 words: 5105.0 sentences: 297.0 pages: flesch: 55.0 cache: ./cache/cord-355397-y69bk5jc.txt txt: ./txt/cord-355397-y69bk5jc.txt summary: Here, we used molecular dynamics (MD) simulations to study the binding of SARS-CoV-2 N-NTD to non-specific (NS) and TRS dsRNAs. We probed dsRNAs'' Watson and Crick (WC) base-pairing over 25 replicas of 100 ns MD simulations, showing that only one N-NTD of dimeric N is enough to destabilize dsRNAs, initiating melting. We calculated the structural model of the N-NTD:dsTRS complex based on the experimental data for the N-NTD interaction with a non-specific dsRNA (5''-CACUGAC-3'') (dsNS) (16) using the HADDOCK 2.2 server (20) . In contrast to the decrease in the number of intramolecular hydrogen bonds between the sense and anti-sense strands of dsRNAs (WC base-pairing) due to N-NTD binding, we observed an increase in the average number of intermolecular hydrogen bonds formed between the nitrogenous bases of dsTRS and N-NTD (protein-RNA interaction) along the 100 ns MD simulation, whereas for dsNS, this average value was constant ( Figure 3B top). abstract: The N protein of betacoronaviruses is responsible for nucleocapsid assembly and other essential regulatory functions. Its N-terminal domain (NTD) interacts and melts the double-stranded transcriptional regulatory sequences (dsTRS), regulating the discontinuous subgenome transcription process. Here, we used molecular dynamics (MD) simulations to study the binding of SARS-CoV-2 N-NTD to non-specific (NS) and TRS dsRNAs. We probed dsRNAs’ Watson and Crick (WC) base-pairing over 25 replicas of 100 ns MD simulations, showing that only one N-NTD of dimeric N is enough to destabilize dsRNAs, initiating melting. N-NTD dsRNA destabilizing activity was more efficient for dsTRS than dsNS. N-NTD dynamics, especially a tweezer-like motion of β2-β3 and 2-β5 loops, played a key role in WC base-pairing destabilization. Based on experimental information available in the literature, we constructed kinetics models for N-NTD-mediated dsRNA melting. Our results support a 1:1 stoichiometry (N-NTD:dsRNA), matching MD simulations and raising different possibilities for N-NTD action: (i) two N-NTDs of dimeric N would act independently, increasing efficiency; (ii) two N-NTDs of dimeric N would bind to two different RNA sites, bridging distant regions of the genome; and (iii) monomeric N would be active, opening up the possibility of a regulatory dissociation event. IMPORTANCE Coronaviruses are among the largest positive-sense RNA viruses. They display a unique discontinous transcription mechanism, involving N protein as a major player. The N-NTD promote the dsRNA melting releasing the nascent sense negative strand via a poorly known mechanism of action. It specifically recognizes the body TRS conserved RNA motif located at the 5’ end of each ORF. N protein has the ability to transfer the nascent RNA strand to the leader TRS. The mechanism is essential and one single mutation at the RNA binding site of the N-NTD impairs the viral replication. Here, we describe a counterintuitive mechanism of action of N-NTD based on molecular dynamics simulation and kinetic modelling of the experimental melting activity of N-NTD. This data impacts directly in the understanding of the way N protein acts in the cell and will guide future experiments. url: https://doi.org/10.1101/2020.08.24.264465 doi: 10.1101/2020.08.24.264465 id: cord-260054-iihgc5nr author: Cavallo, Luigi title: D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly date: 2020-06-08 words: 4062.0 sentences: 210.0 pages: flesch: 59.0 cache: ./cache/cord-260054-iihgc5nr.txt txt: ./txt/cord-260054-iihgc5nr.txt summary: 3D structures are now available from the Protein Data Bank (PDB) (21) for the SARS-CoV-2 S protein in the pre-fusion conformation, also bound to the ACE2 receptor (22) (23) (24) (25) (26) (27) (28) , and for the post-fusion core of its S2 subunit in the postfusion conformation (29) . We downloaded all the SARS-CoV-2 genomic sequences from the GISAID resource on April 21 st 2020, extracted from them 7,692 complete S protein sequences and identified all the point mutations occurring in at least two identical sequences (see Methods). When looking at the post-fusion conformation of the SARS-CoV-2 spike protein S2 subunit, these mutations appear more revealing. Based on a thorough analysis of the S protein sequences, that we extracted from the genomic sequences of SARS-CoV-2 reported in GISAID on April 21 st , we identified the fusion core of the HR1 as a mutational hotspot. abstract: The iconic “red crown” of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made of its spike (S) glycoprotein. The S protein is the Trojan horse of coronaviruses, mediating their entry into the host cells. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On April 21st, the GISAID resource had collected 10,823 SARS-CoV-2 genomic sequences. We extracted from them all the complete S protein sequences and identified point mutations thereof. Six mutations were located on a 14-residue segment (929-943) in the “fusion core” of the heptad repeat 1 (HR1). Our modeling in the pre- and post-fusion S protein conformations revealed, for three of them, the loss of interactions stabilizing the post-fusion assembly. On May 29th, the SARS-CoV-2 genomic sequences in GISAID were 34,805. An analysis of the occurrences of the HR1 mutations in this updated dataset revealed a significant increase for the S929I and S939F mutations and a dramatic increase for the D936Y mutation, which was particularly widespread in Sweden and Wales/England. We notice that this is also the mutation causing the loss of a strong inter-monomer interaction, the D936-R1185 salt bridge, thus clearly weakening the post-fusion assembly. url: https://doi.org/10.1101/2020.06.08.140152 doi: 10.1101/2020.06.08.140152 id: cord-332178-0xyrmk5a author: Chadchan, Sangappa B. title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization date: 2020-06-24 words: 2449.0 sentences: 163.0 pages: flesch: 50.0 cache: ./cache/cord-332178-0xyrmk5a.txt txt: ./txt/cord-332178-0xyrmk5a.txt summary: title: The SARS-CoV-2 receptor, Angiotensin converting enzyme 2 (ACE2) is required for human endometrial stromal cell decidualization STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. Given the important function of the uterine stroma and the possibility that SARS-CoV-2 could infect the uterus, our goal here was to 101 determine whether ACE2 is expressed in endometrial stromal cells, is regulated by progesterone, 102 and is required for decidualization. Given the high ACE2 expression in the human 143 endometrium, SARS-CoV-2 may be able to enter endometrial stromal cells and elicit pathological 144 manifestations in women with COVID-19. abstract: STUDY QUESTION Is SARS-CoV-2 receptor, angiotensin-converting enzyme 2 (ACE 2) expressed in the human endometrium during the menstrual cycle, and does it participate in endometrial decidualization? SUMMARY ANSWER ACE2 protein is highly expressed in human endometrial stromal cells during the secretory phase and is essential for human endometrial stromal cell decidualization. WHAT IS KNOWN ALREADY ACE2 is expressed in numerous human tissues including the lungs, heart, intestine, kidneys and placenta. ACE2 is also the receptor by which SARS-CoV-2 enters human cells. STUDY DESIGN, SIZE, DURATION Proliferative (n = 9) and secretory (n = 6) phase endometrium biopsies from healthy reproductive-age women and primary human endometrial stromal cells from proliferative phase endometrium were used in the study. PARTICIPANTS/MATERIALS, SETTING, METHODS ACE2 expression and localization were examined by qRT-PCR, Western blot, and immunofluorescence in both human endometrial samples and mouse uterine tissue. The effect of ACE2 knockdown on morphological and molecular changes of human endometrial stromal cell decidualization were assessed. Ovariectomized mice were treated with estrogen or progesterone to determine the effects of these hormones on ACE2 expression. MAIN RESULTS AND THE ROLE OF CHANCE In human tissue, ACE2 protein is expressed in both endometrial epithelial and stromal cells in the proliferative phase of the menstrual cycle, and expression increases in stromal cells in the secretory phase. The ACE2 mRNA (P < 0.0001) and protein abundance increased during primary human endometrial stromal cell (HESC) decidualization. HESCs transfected with ACE2-targeting siRNA were less able to decidualize than controls, as evidenced by a lack of morphology change and lower expression of the decidualization markers PRL and IGFBP1 (P < 0.05). In mice during pregnancy, ACE2 protein was expressed in uterine epithelial and stromal cells increased through day six of pregnancy. Finally, progesterone induced expression of Ace2 mRNA in mouse uteri more than vehicle or estrogen (P < 0.05). LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Experiments assessing the function of ACE2 in human endometrial stromal cell decidualization were in vitro. Whether SARS-CoV-2 can enter human endometrial stromal cells and affect decidualization have not been assessed. WIDER IMPLICATIONS OF THE FINDINGS Expression of ACE2 in the endometrium allow SARS-CoV-2 to enter endometrial epithelial and stromal cells, which could impair in vivo decidualization, embryo implantation, and placentation. If so, women with COVID-19 may be at increased risk of early pregnancy loss. STUDY FUNDINGS/COMPETING INTEREST(S) This study was supported by National Institutes of Health / National Institute of Child Health and Human Development grants R01HD065435 and R00HD080742 to RK and Washington University School of Medicine start-up funds to RK. The authors declare that they have no conflicts of interest. url: https://doi.org/10.1101/2020.06.23.168252 doi: 10.1101/2020.06.23.168252 id: cord-326337-s0fp5z1q author: Chan, Kui K. title: An engineered decoy receptor for SARS-CoV-2 broadly binds protein S sequence variants date: 2020-10-19 words: 4573.0 sentences: 256.0 pages: flesch: 54.0 cache: ./cache/cord-326337-s0fp5z1q.txt txt: ./txt/cord-326337-s0fp5z1q.txt summary: Deep mutagenesis of the isolated receptor-binding domain (RBD) by yeast surface display 44 has easily identified mutations in S that retain high expression and ACE2 affinity, yet are no longer bound 45 by monoclonal antibodies and confer resistance (19) . An alternative protein-based antiviral to monoclonal antibodies is to use soluble ACE2 (sACE2) as a 56 decoy to compete for receptor-binding sites on the viral spike (6, (22) (23) (24) (25) of diverse SARS-associated betacoronaviruses that use ACE2 for entry. The sequence 162 diversity observed among natural betacoronaviruses, which display high diversity at the ACE2 binding 163 site, is therefore replicated in the deep mutational scan, which predicts the SARS-CoV-2 spike tolerates 164 substantial genetic diversity at the receptor-binding site for function. From this accessible sequence 165 diversity SARS-CoV-2 might feasibly mutate to acquire resistance to monoclonal antibodies or 166 engineered decoy receptors targeting the ACE2-binding site. abstract: The spike S of SARS-CoV-2 recognizes ACE2 on the host cell membrane to initiate entry. Soluble decoy receptors, in which the ACE2 ectodomain is engineered to block S with high affinity, potently neutralize infection and, due to close similarity with the natural receptor, hold out the promise of being broadly active against virus variants without opportunity for escape. Here, we directly test this hypothesis. We find an engineered decoy receptor, sACE22.v2.4, tightly binds S of SARS-associated viruses from humans and bats, despite the ACE2-binding surface being a region of high diversity. Saturation mutagenesis of the receptor-binding domain followed by in vitro selection, with wild type ACE2 and the engineered decoy competing for binding sites, failed to find S mutants that discriminate in favor of the wild type receptor. We conclude that resistance to engineered decoys will be rare and that decoys may be active against future outbreaks of SARS-associated betacoronaviruses. url: https://doi.org/10.1101/2020.10.18.344622 doi: 10.1101/2020.10.18.344622 id: cord-301535-eui41zyg author: Chandler-Brown, Devon title: A Highly Scalable and Rapidly Deployable RNA Extraction-Free COVID-19 Assay by Quantitative Sanger Sequencing date: 2020-04-10 words: 4143.0 sentences: 228.0 pages: flesch: 52.0 cache: ./cache/cord-301535-eui41zyg.txt txt: ./txt/cord-301535-eui41zyg.txt summary: This assay uses the addition of a frame-shifted spike-in, a modified PCR master mix, and custom Sanger sequencing data analysis to detect and quantify SARS-CoV-2 RNA at a limit of detection comparable to existing qPCR-based assays, at 10-20 genome copy equivalents. Crucially, our assay was able to detect SARS-CoV-2 RNA from viral particles suspended in transport media that was directly added to the PCR master mix, suggesting that RNA extraction can be skipped entirely without any degradation of test performance. Quantitative analysis of the Sanger sequence chromatogram gives qSanger an extremely high sensitivity and specificity for all positive results with a limit of detection of 10-20 genome copy equivalents (GCE), equivalent to gold-standard qPCR methods. To further evaluate the feasibility of a direct VTM, extraction-free method for Sars-CoV-2 detection, we also examined the ability of qSanger to quantify the amount of viral particles in the Seracare positive control specimens (Fig. 3B ). abstract: There is currently an urgent unmet need to increase coronavirus disease 2019 (COVID-19) testing capability to effectively respond to the COVID-19 pandemic. However, the current shortage in RNA extraction reagents as well as limitations in qPCR protocols have resulted in bottlenecks in testing capacity. Herein, we describe a novel molecular diagnostic for COVID-19 based on Sanger sequencing. This assay uses the addition of a frame-shifted spike-in, a modified PCR master mix, and custom Sanger sequencing data analysis to detect and quantify SARS-CoV-2 RNA at a limit of detection comparable to existing qPCR-based assays, at 10-20 genome copy equivalents. Crucially, our assay was able to detect SARS-CoV-2 RNA from viral particles suspended in transport media that was directly added to the PCR master mix, suggesting that RNA extraction can be skipped entirely without any degradation of test performance. Since Sanger sequencing instruments are widespread in clinical laboratories and commonly have built-in liquid handling automation to support up to 3840 samples per instrument per day, the widespread adoption of qSanger COVID-19 diagnostics can unlock more than 1,000,000 tests per day in the US. url: https://doi.org/10.1101/2020.04.07.029199 doi: 10.1101/2020.04.07.029199 id: cord-102366-2alcsd1p author: Cheek, Martin title: Taxonomic revision of the threatened African genus Pseudohydrosme Engl. (Araceae), with P. ebo, a new, Critically Endangered species from Ebo, Cameroon date: 2020-10-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This is the first revision in nearly 130 years of the African genus Pseudohydrosme, formerly considered endemic to Gabon. Sister to Anchomanes, Pseudohydrosme is distinct from Anchomanes because of its 2–3-locular ovary (not unilocular), peduncle concealed by cataphylls at anthesis and far shorter than the spathe (not exposed, far exceeding the spathe), stipitate fruits and viviparous (vegetatively apomictic) roots (not sessile, roots non-viviparous). Three species, one new to science, are recognised, in two sections. Although doubt has previously been cast on the value of recognising Pseudohydrosme buettneri, of Gabon, it is here accepted and maintained as a distinct species in the monotypic section, Zyganthera. However, it is considered to be probably globally extinct. Pseudohydrosme gabunensis, type species of the genus, also Gabonese, is maintained in Sect. Pseudohydrosme together with Pseudohydrosme ebo sp.nov. of the Ebo Forest, Littoral, Cameroon, the first addition to the genus since the nineteenth century, and which extends the range of the genus 450 km north from Gabon, into the Cross-Sanaga biogeographic area. The discovery of Pseudohydrosme ebo resulted from a series of surveys for conservation management in Cameroon, and triggered this paper. All three species of Pseudohydrosme are morphologically characterised, their habitat and biogeography discussed, and their extinction risks are respectively assessed as Critically Endangered (Possibly Extinct), Endangered and Critically Endangered using the IUCN standard. Clearance of forest habitat for logging, followed by agriculture or urbanisation are major threats. One of the species may occur in a formally protected areas and is also cultivated widely but infrequently in Europe and the USA for its spectacular inflorescences. url: https://doi.org/10.1101/2020.10.05.326850 doi: 10.1101/2020.10.05.326850 id: cord-104025-ysxc7rpl author: Cheek, Martin title: Deinbollia onanae (Sapindaceae), a new, Endangered, montane tree species from the Cameroon Highlands date: 2020-10-26 words: 3999.0 sentences: 235.0 pages: flesch: 61.0 cache: ./cache/cord-104025-ysxc7rpl.txt txt: ./txt/cord-104025-ysxc7rpl.txt summary: title: Deinbollia onanae (Sapindaceae), a new, Endangered, montane tree species from the Cameroon Highlands Deinbollia onanae is an infrequent tree species known from five locations in surviving islands of montane (or upper submontane) forest along the line of the Cameroon Highlands. As part of the project to designate Important Plant Areas (IPAs) in Cameroon (also known as Tropical Important Plant Areas or TIPAs), we are striving to name, assess the conservation status and include in IPAs (Darbyshire et al., 2017) rare and threatened plant species in the surviving, threatened natural habitat of the Cross-Sanaga interval (Cheek et al., 2001) . Apart from Deinbollia onanae, the only other montane tree species endemic to the Cameroon Highland chain are the nearly extinct Ternstroemia cameroonensis Cheek (Cheek et al., 2017) and the more common and widespread Schleffera mannii (Hook.f.)Harms (Keay, 1958) . abstract: Deinbollia onanae (Sapindaceae-Litchi clade) is here formally named and characterised as a new species to science, previously known as Deinbollia sp. 2. Cameroon has the highest species-diversity and species endemism known in this African-Western Indian Ocean genus of 42 species. Deinbollia onanae is an infrequent tree species known from five locations in surviving islands of montane (or upper submontane) forest along the line of the Cameroon Highlands. It is here assessed as Endangered according to the IUCN 2012 standard, threatened mainly by clearance of forest for agriculture. The majority of tree species characteristic of montane forest (above 2000 m alt.) in the Cameroon Highlands are also widespread in East African mountains (i.e. are Afromontane). Deinbollia onanae is one of only a very small number of species that are endemic (globally restricted to) the mountain range. It is postulated that this new species is in a sister relationship with Deinbollia oreophila, which is a frequent species of a lower (submontane) altitudinal band of the same range. It is further postulated that seed dispersal is or was by frugivorous birds, potentially turacos, alternatively by primates such as Preuss s monkey. url: https://doi.org/10.1101/2020.10.24.353680 doi: 10.1101/2020.10.24.353680 id: cord-276017-2375ipkk author: Chen, Dongsheng title: Single-cell screening of SARS-CoV-2 target cells in pets, livestock, poultry and wildlife date: 2020-06-14 words: 4132.0 sentences: 365.0 pages: flesch: 70.0 cache: ./cache/cord-276017-2375ipkk.txt txt: ./txt/cord-276017-2375ipkk.txt summary: Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Previous studies have proposed that animal tissues show high heterogeneity in terms of cellular composition and gene expression profiles 15 , and ACE2 is only expressed in a small proportion of specific cell populations 16 , making single cell analysis of SARS-CoV-2 target cells an attracting field to investigate. Here, we constructed the single cell atlas for livestock, poultry, pets and wildlife, then screened putative SARS-CoV-2 target cells (indicated by the co-expression patterns of SARS-CoV-2 entry receptor ACE2 and SARS-CoV-2 entry activator TMPRSS2) and systematically evaluated their susceptibility, with the aim to understand the virus transmission routes and provide clues to fight against COVID-19. abstract: A few animals have been suspected to be intermediate hosts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, a large-scale single-cell screening of SARS-CoV-2 target cells on a wide variety of animals is missing. Here, we constructed the single-cell atlas for 11 representative species in pets, livestock, poultry, and wildlife. Notably, the proportion of SARS-CoV-2 target cells in cat was found considerably higher than other species we investigated and SARS-CoV-2 target cells were detected in multiple cell types of domestic pig, implying the necessity to carefully evaluate the risk of cats during the current COVID-19 pandemic and keep pigs under surveillance for the possibility of becoming intermediate hosts in future coronavirus outbreak. Furthermore, we screened the expression patterns of receptors for 144 viruses, resulting in a comprehensive atlas of virus target cells. Taken together, our work provides a novel and fundamental strategy to screen virus target cells and susceptible species, based on single-cell transcriptomes we generated for domesticated animals and wildlife, which could function as a valuable resource for controlling current pandemics and serve as an early warning system for coping with future infectious disease threats. url: https://doi.org/10.1101/2020.06.13.149690 doi: 10.1101/2020.06.13.149690 id: cord-314321-klb8oe9q author: Chen, Serena H. title: Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets date: 2020-04-18 words: 3168.0 sentences: 174.0 pages: flesch: 52.0 cache: ./cache/cord-314321-klb8oe9q.txt txt: ./txt/cord-314321-klb8oe9q.txt summary: Recent experimental structures of the SARS-CoV-2 S protein receptor binding domain (RBD) in complex with ACE2 provide detailed interface information [4] , [6] ; targeting this interface represents an active area of research for therapeutic development [11] . By first comparing the S protein protomer structure of SARS-CoV-2 to those from previous human coronaviruses, we identified distinct clusters for each virus in the 3-D latent space, where representative structures from these clusters highlight their differences in domain flexibility. To further understand the molecular structures of different human coronavirus S proteins and the oligomeric state of SARS-CoV-2 S protein, we deployed a custom-built deep learning architecture, a convolutional variational autoencoder (CVAE), to encode the high dimensional protein structures from the MD simulations into lower dimensional latent spaces. The size of each resulting matrix was also 191 ⇥ 191, and we merged a total of 10,000 distance matrices of the protomer and trimer of SARS-CoV-2 S protein. abstract: The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19. url: https://doi.org/10.1101/2020.04.17.047548 doi: 10.1101/2020.04.17.047548 id: cord-102226-aioqogaw author: Chiu, Elliott S. title: Presence of endogenous viral elements negatively correlates with FeLV susceptibility in puma and domestic cat cells date: 2020-06-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: While feline leukemia virus (FeLV) has been shown to infect felid species other than the endemic domestic cat host, differences in FeLV susceptibility among species has not been evaluated. Previous reports have noted a negative correlation between enFeLV copy number and exogenous FeLV infection outcomes in domestic cats. Since felids outside the genus Felis do not harbor enFeLV genomes, we hypothesized absence of enFeLV results in more severe disease consequences in felid species lacking these genomic elements. We infected primary fibroblasts isolated from domestic cats (Felis catus) and pumas (Puma concolor) with FeLV and quantitated proviral and viral antigen loads. Domestic cat enFeLV env and LTR copy numbers were determined for each individual and compared to FeLV viral outcomes. FeLV proviral and antigen levels were also measured in 6 naturally infected domestic cats and 11 naturally infected Florida panthers (P. concolor coryi). We demonstrated that puma fibroblasts are more permissive to FeLV than domestic cat cells, and domestic cat FeLV restriction was highly related to enFeLV LTR copy number. Terminal tissues from FeLV-infected Florida panthers and domestic cats had similar exFeLV proviral copy numbers, but Florida panther tissues have higher FeLV antigen loads. Our work indicates enFeLV LTR elements negatively regulate exogenous FeLV replication. Further, Puma concolor lacking enFeLV are more permissive to FeLV infection than domestic cats, suggesting endogenization can play a beneficial role in mitigating exogenous retroviral infections. Conversely, presence of endogenous retroelements may relate to new host susceptibility during viral spillover events. Importance Feline leukemia virus (FeLV) can infect a variety of felid species. Only the primary domestic cat host and related small cat species harbor a related endogenous virus in their genomes. Previous studies noted a negative association between the endogenous virus copy number and exogenous virus infection in domestic cats. This report shows that puma cells, which lack endogenous FeLV, produce more virus more rapidly than domestic cat fibroblasts following cell culture challenge. We document a strong association between domestic cat cell susceptibility and FeLV long terminal repeat (LTR) copy number, similar to observations in natural FeLV infections. Viral replication does not, however, correlate with FeLV env copy number, suggesting this effect is specific to FeLV LTR elements. This discovery indicates a protective capacity of the endogenous virus against the exogenous form, either via direct interference or indirectly via gene regulation, and may suggest evolutionary outcomes of retroviral endogenization. url: https://doi.org/10.1101/2020.06.23.168351 doi: 10.1101/2020.06.23.168351 id: cord-334891-4jgtxg07 author: Choudhury, Abhigyan title: In silico analyses on the comparative sensing of SARS-CoV-2 mRNA by intracellular TLRs of human date: 2020-11-11 words: 2926.0 sentences: 169.0 pages: flesch: 54.0 cache: ./cache/cord-334891-4jgtxg07.txt txt: ./txt/cord-334891-4jgtxg07.txt summary: This study is hoped to rationalize the comparative binding and sensing of SARS-CoV-2 mRNA towards the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drive these reactions. Our in-silico study on the binding of all mRNAs with the intracellular TLRs shown that the mRNA of NSP10, S2, and E proteins of SARS-CoV-2 are potent enough to bind with TLR3, TLR9, and TLR7 and trigger downstream cascade reactions, and may be used as an option for validation of therapeutic option and immunomodulation against COVID-19. The binding of Spike protein with the human ACE2 receptor triggers the pathogenesis 3 of the SARS-CoV-2, leading to the activation of TLRs to activate the proliferation and 4 production of pro-inflammatory cytokines causing cytokine storm, those results in 5 inflammations. abstract: The worldwide outbreak of COVID-19 pandemic caused by SARS-CoV-2 leads to loss of mankind and global economic stability. The continuous spreading of the disease and its pathogenesis takes millions of lives of peoples and the unavailability of appropriate therapeutic strategy makes it much more severe. Toll-like receptors (TLRs) are the crucial mediators and regulators of host immunity. The role of several TLRs in immunomodulation of host by SARS-CoV-2 is recently demonstrated. However, the functionality of human intracellular TLRs including TLR3,7,8 and 9 is still being untested for sensing of viral RNA. This study is hoped to rationalize the comparative binding and sensing of SARS-CoV-2 mRNA towards the intracellular TLRs, considering the solvent-based force-fields operational in the cytosolic aqueous microenvironment that predominantly drive these reactions. Our in-silico study on the binding of all mRNAs with the intracellular TLRs shown that the mRNA of NSP10, S2, and E proteins of SARS-CoV-2 are potent enough to bind with TLR3, TLR9, and TLR7 and trigger downstream cascade reactions, and may be used as an option for validation of therapeutic option and immunomodulation against COVID-19. url: https://doi.org/10.1101/2020.11.11.377713 doi: 10.1101/2020.11.11.377713 id: cord-309556-xv3413k1 author: Chow, Ryan D. title: The aging transcriptome and cellular landscape of the human lung in relation to SARS-CoV-2 date: 2020-04-15 words: 5761.0 sentences: 373.0 pages: flesch: 53.0 cache: ./cache/cord-309556-xv3413k1.txt txt: ./txt/cord-309556-xv3413k1.txt summary: In aggregate, these analyses showed that the age-associated genes with functional roles in SARS-CoV are expressed in specific cell types of the human lung. Of note, the overlap between lung ageassociated genes and SARS-CoV-2 regulated genes was statistically significant across all 3 cell lines (Figure 6d-f) , suggesting a degree of similarity between the transcriptional changes associated with aging and with SARS-CoV-2 infection. Among the age-associated genes that were induced by SARS-CoV-2 infection, the majority of these genes increase in expression with age (Cluster 1) (Figure 6g-i) . To identify a consensus set of age-associated genes that are regulated by SARS-CoV-2 infection, we integrated the analyses from all 3 cell lines. By integrating these data with single cell transcriptomes of human lung tissue, we further pinpointed the specific cell types that normally express the age-associated genes. abstract: Since the emergence of SARS-CoV-2 in December 2019, Coronavirus Disease-2019 (COVID-19) has rapidly spread across the globe. Epidemiologic studies have demonstrated that age is one of the strongest risk factors influencing the morbidity and mortality of COVID-19. Here, we interrogate the transcriptional features and cellular landscapes of the aging human lung through integrative analysis of bulk and single-cell transcriptomics. By intersecting these age-associated changes with experimental data on host interactions between SARS-CoV-2 or its relative SARS-CoV, we identify several age-associated factors that may contribute to the heightened severity of COVID-19 in older populations. We observed that age-associated gene expression and cell populations are significantly linked to the heightened severity of COVID-19 in older populations. The aging lung is characterized by increased vascular smooth muscle contraction, reduced mitochondrial activity, and decreased lipid metabolism. Lung epithelial cells, macrophages, and Th1 cells decrease in abundance with age, whereas fibroblasts, pericytes and CD4+ Tcm cells increase in abundance with age. Several age-associated genes have functional effects on SARS-CoV replication, and directly interact with the SARS-CoV-2 proteome. Interestingly, age-associated genes are heavily enriched among those induced or suppressed by SARS-CoV-2 infection. These analyses illuminate potential avenues for further studies on the relationship between the aging lung and COVID-19 pathogenesis, which may inform strategies to more effectively treat this disease. url: https://doi.org/10.1101/2020.04.07.030684 doi: 10.1101/2020.04.07.030684 id: cord-328644-odtue60a author: Comandatore, Francesco title: Insurgence and worldwide diffusion of genomic variants in SARS-CoV-2 genomes date: 2020-05-28 words: 6535.0 sentences: 301.0 pages: flesch: 50.0 cache: ./cache/cord-328644-odtue60a.txt txt: ./txt/cord-328644-odtue60a.txt summary: These variants might arise during the spread of the epidemic, as viruses are known for their high frequency of mutation, particularly in single stranded RNA viruses -as in the case of SARS-CoV-2 (Sanjuán and Domingo-Calap 2016) , which has a single, positive-strand RNA genome. To have a better insight on the history and spread of the COVID-19 pandemic in Italy and thanks to the sequences deposited in the Gisaid database, we identified 7 non synonymous mutations that are differentially frequent in Italian SARS-CoV-2 strains respect to strains circulating globally. Our analysis allowed us to identify 7 positions in four proteins that present drastic changes in amino acid frequencies when comparing Italian sequences with worldwide sequences available on Gisaid.org on April, 10, 2020 ( Figure 1 ). abstract: The SARS-CoV-2 pandemic that we are currently experiencing is exerting a massive toll both in human lives and economic impact. One of the challenges we must face is to try to understand if and how different variants of the virus emerge and change their frequency in time. Such information can be extremely valuable as it may indicate shifts in aggressiveness, and it could provide useful information to trace the spread of the virus in the population. In this work we identified and traced over time 7 amino acid variants that are present with high frequency in Italy and Europe, but that were absent or present at very low frequencies during the first stages of the epidemic in China and the initial reports in Europe. The analysis of these variants helps defining 6 phylogenetic clades that are currently spreading throughout the world with changes in frequency that are sometimes very fast and dramatic. In the absence of conclusive data at the time of writing, we discuss whether the spread of the variants may be due to a prominent founder effect or if it indicates an adaptive advantage. url: https://doi.org/10.1101/2020.04.30.071027 doi: 10.1101/2020.04.30.071027 id: cord-103430-x6zzuu7v author: Contu, Lara title: Characterisation of the Semliki Forest Virus-host cell interactome reveals the viral capsid protein as an inhibitor of nonsense-mediated mRNA decay date: 2020-10-12 words: 8272.0 sentences: 461.0 pages: flesch: 56.0 cache: ./cache/cord-103430-x6zzuu7v.txt txt: ./txt/cord-103430-x6zzuu7v.txt summary: Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus'' hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. Gene ontology (GO) enrichment analyses of protein complexes that could 10 form between the identified host interactors revealed highly significant GO terms related to 11 translation and Nonsense-mediated mRNA Decay (NMD). In addition to ribosomal proteins, many other RNA binding proteins were also 37 identified as having a potential role in SFV replication (Figure 3a (nsP1, nsP2, nsP3-Z, nsP4, capsid and Env) as well as for the merged list (All baits) was also applied. abstract: The positive-sense, single-stranded RNA alphaviruses pose a potential epidemic threat. Understanding the complex interactions between the viral and the host cell proteins is crucial for elucidating the mechanisms underlying successful virus replication strategies and for developing specific antiviral interventions. Here we present the first comprehensive protein-protein interaction map between the proteins of Semliki Forest Virus (SFV), a mosquito-borne member of the alphaviruses, and host cell proteins. Among the many identified cellular interactors of SFV proteins, the enrichment of factors involved in translation and nonsense-mediated mRNA decay (NMD) was striking, reflecting the virus’ hijacking of the translation machinery and indicating viral countermeasures for escaping NMD by inhibiting NMD at later time points during the infectious cycle. In addition to observing a general inhibition of NMD about 4 hours post infection, we also demonstrate that transient expression of the SFV capsid protein is sufficient to inhibit NMD in cells, suggesting that the massive production of capsid protein during the SFV reproduction cycle is responsible for NMD inhibition. url: https://doi.org/10.1101/2020.10.12.335497 doi: 10.1101/2020.10.12.335497 id: cord-270919-0hldozml author: Cortey, Martí title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins date: 2020-05-17 words: 1063.0 sentences: 73.0 pages: flesch: 56.0 cache: ./cache/cord-270919-0hldozml.txt txt: ./txt/cord-270919-0hldozml.txt summary: title: SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic offers a unique opportunity to study the introduction and evolution of a pathogen into a completely naïve human population. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%. 54 The aim of the present study was to determine the amino acid substitutions in viral 55 proteins that were widely present in available sequences of SARS-CoV-2, relating them 56 to the known chronology of the pandemic. abstract: The Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic offers a unique opportunity to study the introduction and evolution of a pathogen into a completely naïve human population. We identified and analysed the amino acid mutations that gained prominence worldwide in the early months of the pandemic. Eight mutations have been identified along the viral genome, mostly located in conserved segments of the structural proteins and showing low variability among coronavirus, which indicated that they might have a functional impact. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%. url: https://doi.org/10.1101/2020.05.16.099499 doi: 10.1101/2020.05.16.099499 id: cord-102158-5xg40s4o author: Coulibali, Zonlehoua title: Site-specific machine learning predictive fertilization models for potato crops in Eastern Canada date: 2020-03-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Statistical modeling is commonly used to relate the performance of potato (Solanum tuberosum L.) to fertilizer requirements. Prescribing optimal nutrient doses is challenging because of the involvement of many variables including weather, soils, land management, genotypes, and severity of pests and diseases. Where sufficient data are available, machine learning algorithms can be used to predict crop performance. The objective of this study was to predict tuber yield and quality (size and specific gravity) as impacted by nitrogen, phosphorus and potassium fertilization as well as weather, soils and land management variables. We exploited a data set of 273 field experiments conducted from 1979 to 2017 in Quebec (Canada). We developed, evaluated and compared predictions from a hierarchical Mitscherlich model, k-nearest neighbors, random forest, neuronal networks and Gaussian processes. Machine learning models returned R2 values of 0.49–0.59 for tuber marketable yield prediction, which were higher than the Mitscherlich model R2 (0.37). The models were more likely to predict medium-size tubers (R2 = 0.60–0.69) and tuber specific gravity (R2 = 0.58–0.67) than large-size tubers (R2 = 0.55–0.64) and marketable yield. Response surfaces from the Mitscherlich model, neural networks and Gaussian processes returned smooth responses that agreed more with actual evidence than discontinuous curves derived from k-nearest neighbors and random forest models. When marginalized to obtain optimal dosages from dose-response surfaces given constant weather, soil and land management conditions, some disagreements occurred between models. Due to their built-in ability to develop recommendations within a probabilistic risk-assessment framework, Gaussian processes stood out as the most promising algorithm to support decisions that minimize economic or agronomic risks. url: https://doi.org/10.1101/2020.03.12.988626 doi: 10.1101/2020.03.12.988626 id: cord-311066-62edsbfc author: Cox, Brian J. title: Integration of viral transcriptome sequencing with structure and sequence motifs predicts novel regulatory elements in SARS-CoV-2 date: 2020-06-24 words: 2926.0 sentences: 172.0 pages: flesch: 61.0 cache: ./cache/cord-311066-62edsbfc.txt txt: ./txt/cord-311066-62edsbfc.txt summary: Analysis of SARS-CoV-2 RNA sequencing data from whole RNA transcriptomes identified TRS dependent and independent transcripts. Integration of transcripts and 5''-UTR sequence motifs identified that the pentaloop and the stem-loop 3 were also located upstream of spliced genes. Some RNAs, especially non-coding RNAs, generally lack a poly-A tail, which could explain poor detection of TRS independent sgmRNAs. Using published sequencing data of ribosome depleted total RNA from SARS-CoV-2 infected cells and animals (Blanco-Melo et al., 2020) , I aligned these against the viral genome (Figure 2) . Using the aligned reads, I generated transcript models using stringtie, which identified multiple spliced species that aligned with the TRS-L templated events (Figure 2) . Split reads also identified TRS-independent sgmRNAs. In support of my observations on SARS-CoV-2, I also assessed SARS-CoV and MERs transcriptional data, two other human pathogenic CoV. I also identified the TIR motif, a novel sequence element (ATTGGC) flanking the spliced regions of TRS independent sgmRNAs in both SARS-CoV-2 and SARS-CoV. abstract: In the last twenty years, three separate coronaviruses have left their typical animal hosts and became human pathogens. An area of research interest is coronavirus transcription regulation that uses an RNA-RNA mediated template-switching mechanism. It is not known how different transcriptional stoichiometries of each viral gene are generated. Analysis of SARS-CoV-2 RNA sequencing data from whole RNA transcriptomes identified TRS dependent and independent transcripts. Integration of transcripts and 5’-UTR sequence motifs identified that the pentaloop and the stem-loop 3 were also located upstream of spliced genes. TRS independent transcripts were detected as likely non-polyadenylated. Additionally, a novel conserved sequence motif was discovered at either end of the TRS independent splice junctions. While similar both SARS viruses generated similar TRS independent transcripts they were more abundant in SARS-CoV-2. TRS independent gene regulation requires investigation to determine its relationship to viral pathogenicity. url: https://doi.org/10.1101/2020.06.24.169144 doi: 10.1101/2020.06.24.169144 id: cord-102151-26lumewy author: Cox, Robert M. title: Therapeutic Targeting of Measles Virus Polymerase with ERDRP-0519 Suppresses All RNA Synthesis Activity date: 2020-09-24 words: 1797.0 sentences: 92.0 pages: flesch: 43.0 cache: ./cache/cord-102151-26lumewy.txt txt: ./txt/cord-102151-26lumewy.txt summary: Results demonstrate that unlike all other mononegavirus small molecule inhibitors identified to date, ERDRP-0519 inhibits all phosphodiester bond formation in both de novo initiation of RNA synthesis at the promoter and RNA elongation by a committed polymerase complex. Photocrosslinking and resistance profiling-informed ligand docking revealed that this unprecedented mechanism of action of ERDRP-0519 is due to simultaneous engagement of the L protein polyribonucleotidyl transferase (PRNTase)-like domain and the flexible intrusion loop by the compound, pharmacologically locking the polymerase in pre-initiation conformation. Photocrosslinking-based target site 27 mapping demonstrated that this class-defining prototype inhibitor stabilizes a pre-initiation conformation 28 of the viral polymerase complex that sterically cannot accommodate template RNA. Photocrosslinking-based target site 27 mapping demonstrated that this class-defining prototype inhibitor stabilizes a pre-initiation conformation 28 of the viral polymerase complex that sterically cannot accommodate template RNA. abstract: Morbilliviruses, such as measles virus (MeV) and canine distemper virus (CDV), are highly infectious members of the paramyxovirus family. MeV is responsible for major morbidity and mortality in non-vaccinated populations. ERDRP-0519, a pan-morbillivirus small molecule inhibitor for the treatment of measles, targets the morbillivirus RNA-dependent RNA-polymerase (RdRP) complex and displayed unparalleled oral efficacy against lethal infection of ferrets with CDV, an established surrogate model for human measles. Resistance profiling identified the L subunit of the RdRP, which harbors all enzymatic activity of the polymerase complex, as the molecular target of inhibition. Here, we examined binding characteristics, physical docking site, and the molecular mechanism of action of ERDRP-0519 through label-free biolayer interferometry, photoaffinity cross-linking, and in vitro RdRP assays using purified MeV RdRP complexes and synthetic templates. Results demonstrate that unlike all other mononegavirus small molecule inhibitors identified to date, ERDRP-0519 inhibits all phosphodiester bond formation in both de novo initiation of RNA synthesis at the promoter and RNA elongation by a committed polymerase complex. Photocrosslinking and resistance profiling-informed ligand docking revealed that this unprecedented mechanism of action of ERDRP-0519 is due to simultaneous engagement of the L protein polyribonucleotidyl transferase (PRNTase)-like domain and the flexible intrusion loop by the compound, pharmacologically locking the polymerase in pre-initiation conformation. This study informs selection of ERDRP-0519 as clinical candidate for measles therapy and identifies a previously unrecognized druggable site in mononegavirus L polymerase proteins that can silence all synthesis of viral RNA. Importance The mononegavirus order contains major established and recently emerged human pathogens. Despite the threat to human health, antiviral therapeutics directed against this order remain understudied. The mononegavirus polymerase complex represents a promising drug target due to its central importance for both virus replication and viral mitigation of the innate host antiviral response. In this study, we have mechanistically characterized a clinical candidate small-molecule MeV polymerase inhibitor. The compound blocked all phosphodiester bond formation activity, a unique mechanism of action unlike all other known mononegavirus polymerase inhibitors. Photocrosslinking-based target site mapping demonstrated that this class-defining prototype inhibitor stabilizes a pre-initiation conformation of the viral polymerase complex that sterically cannot accommodate template RNA. Function-equivalent druggable sites exist in all mononegavirus polymerases. In addition to its direct anti-MeV impact, the insight gained in this study can therefore serve as a blueprint for indication spectrum expansion through structure-informed scaffold engineering or targeted drug discovery. url: https://doi.org/10.1101/2020.09.23.311043 doi: 10.1101/2020.09.23.311043 id: cord-329504-91te3nu8 author: Croll, Tristan title: Making the invisible enemy visible date: 2020-10-07 words: 4826.0 sentences: 219.0 pages: flesch: 52.0 cache: ./cache/cord-329504-91te3nu8.txt txt: ./txt/cord-329504-91te3nu8.txt summary: A general indication of how well the atomic model fits the measurement data can be obtained by comparing the deposited R-factors to results from PDB-REDO (10) (including Whatcheck (11)) to determine the overall density fit as well as many other diagnostics. Our remodelled structure is offering a valuable structural basis for future studies, such as in-silico docking and drug design targeting at SARS-CoV-2 RdRp (34), as well as for computational modelling or simulations to investigate the molecular mechanism of viral replication (31, 35, 36) . This has included a number of posts on our homepage aimed at non-scientists and live streaming the reprocessing of data on Twitch, as well as the design, production, and public release of an accurate 3D printed model of SARS-CoV-2 based on deposited structures for use as a prop for outreach activities. abstract: During the COVID-19 pandemic, structural biologists have rushed to solve the structures of the 28 proteins encoded by the SARS-CoV-2 genome in order to understand the viral life cycle and enable structure-based drug design. In addition to the 200 structures from SARS-CoV previously solved, 367 structures covering 16 of the viral proteins have been released in the span of only 6 months. These structural models serve as basis for research worldwide to understand how the virus hijacks human cells, for structure-based drug design and to aid in the development of vaccines. However, errors often occur in even the most careful structure determination - and are even more common among these structures, which were solved under immense pressure. From the beginning of the pandemic, the Coronavirus Structural Taskforce has categorized, evaluated and reviewed all of these experimental protein structures in order to help downstream users and original authors. Our website also offers improved models for many key structures, which have been used by Folding@Home, OpenPandemics, the EU JEDI COVID-19 challenge, and others. Here, we describe our work for the first time, give an overview of common problems, and describe a few of these structures that have since acquired better versions in the worldwide Protein Data Bank, either from new data or as depositor re-versions using our suggested changes. url: https://doi.org/10.1101/2020.10.07.307546 doi: 10.1101/2020.10.07.307546 id: cord-265277-ymvrserl author: Crooke, Stephen N. title: Immunoinformatic identification of B cell and T cell epitopes in the SARS-CoV-2 proteome date: 2020-05-14 words: 4620.0 sentences: 249.0 pages: flesch: 52.0 cache: ./cache/cord-265277-ymvrserl.txt txt: ./txt/cord-265277-ymvrserl.txt summary: A final round of selection on the basis of HLA 197 promiscuity (i.e., predicted binding to > 3 HLA molecules) and predicted antigenicity scoring using the 198 VaxiJen 2.0 server produced a subset of five candidate peptides (four ORF1ab, one S protein) as potential 199 targets for vaccine development (Table 1) with the hypothesis that increased HLA binding promiscuity 200 meant broader population base coverage by those peptides. As selective pressures are known to introduce viral mutations that promote fitness and can lead 266 to evasion of immune responses (59, 60), we first sought to investigate the genetic similarity of all 267 reported SARS-CoV-2 clinical isolates and identify a consensus sequence for use in our epitope 268 prediction studies. An increasing number of studies have employed predictive algorithms to identify potential HLA 285 class I epitopes for SARS-CoV-2, although relatively few have comprehensively analyzed the entire viral 286 proteome. abstract: A novel coronavirus (SARS-CoV-2) emerged from China in late 2019 and rapidly spread across the globe, infecting millions of people and generating societal disruption on a level not seen since the 1918 influenza pandemic. A safe and effective vaccine is desperately needed to prevent the continued spread of SARS-CoV-2; yet, rational vaccine design efforts are currently hampered by the lack of knowledge regarding viral epitopes targeted during an immune response, and the need for more in-depth knowledge on betacoronavirus immunology. To that end, we developed a computational workflow using a series of open-source algorithms and webtools to analyze the proteome of SARS-CoV-2 and identify putative T cell and B cell epitopes. Using increasingly stringent selection criteria to select peptides with significant HLA promiscuity and predicted antigenicity, we identified 41 potential T cell epitopes (5 HLA class I, 36 HLA class II) and 6 potential B cell epitopes, respectively. Docking analysis and binding predictions demonstrated enrichment for peptide binding to HLA-B (class I) and HLA-DRB1 (class II) molecules. Overlays of predicted B cell epitopes with the structure of the viral spike (S) glycoprotein revealed that 4 of 6 epitopes were located in the receptor-binding domain of the S protein. To our knowledge, this is the first study to comprehensively analyze all 10 (structural, non-structural and accessory) proteins from SARS-CoV-2 using predictive algorithms to identify potential targets for vaccine development. Significance Statement The novel coronavirus SARS-CoV-2 recently emerged from China, rapidly spreading and ushering in a global pandemic. Despite intensive research efforts, our knowledge of SARS-CoV-2 immunology and the proteins targeted by the immune response remains relatively limited, making it difficult to rationally design candidate vaccines. We employed a suite of bioinformatic tools, computational algorithms, and structural modeling to comprehensively analyze the entire SARS-CoV-2 proteome for potential T cell and B cell epitopes. Utilizing a set of stringent selection criteria to filter peptide epitopes, we identified 41 T cell epitopes (5 HLA class I, 36 HLA class II) and 6 B cell epitopes that could serve as promising targets for peptide-based vaccine development against this emerging global pathogen. url: https://doi.org/10.1101/2020.05.14.093757 doi: 10.1101/2020.05.14.093757 id: cord-344909-0o55l4iy author: Cross, Robert W. title: Use of convalescent serum reduces severity of COVID-19 in nonhuman primates date: 2020-10-14 words: 5711.0 sentences: 291.0 pages: flesch: 49.0 cache: ./cache/cord-344909-0o55l4iy.txt txt: ./txt/cord-344909-0o55l4iy.txt summary: However, and importantly, lower levels of SARS-CoV-2 in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several parameters associated with coagulation and inflammatory processes were observed in monkeys that received convalescent sera versus untreated controls. Differences in clinical parameters of the LD-treated group with untreated control animals from this study or historical control animals were minimal; however, the lack of infectious SARS-CoV-2 in the BAL samples from all of the LD-treated animals and reduced lung pathology suggest that an antiviral effect was present despite the lower concentration of neutralizing antibodies in the dose of convalescent sera administered. PRNT50 assays were performed on pooled convalescent sera from AGMs challenged with the homologous isolate of SARS-CoV-2 in previous studies (Cross et al., 2020; Woolsey et al., 2020) compared with control animals on day 2 post infection (d) and abstract: Passive transfer of convalescent plasma or serum is a time-honored strategy for treating infectious diseases. Human convalescent plasma containing antibodies against SARS-CoV-2 is currently being used to treat COVID-19 patients. However, most patients have been treated outside of randomized clinical trials making it difficult to determine the efficacy of this approach. Here, we assessed the efficacy of convalescent sera in a newly developed African green monkey model of COVID-19. Groups of SARS-CoV-2-infected animals were treated with pooled convalescent sera containing either high or low to moderate anti-SARS-CoV-2 neutralizing antibody titers. Differences in viral load and disease pathology were minimal between monkeys that received the lower titer convalescent sera and untreated controls. However, and importantly, lower levels of SARS-CoV-2 in respiratory compartments, reduced gross and histopathological lesion severity in the lungs, and reductions in several parameters associated with coagulation and inflammatory processes were observed in monkeys that received convalescent sera versus untreated controls. Our data support human studies suggesting that convalescent plasma therapy is an effective strategy if donors with high level of antibodies against SARS-CoV-2 are employed and if recipients are at an early stage of disease. url: https://doi.org/10.1101/2020.10.14.340091 doi: 10.1101/2020.10.14.340091 id: cord-302146-51hof7it author: Cross, Thomas J. title: Sequence characterization and molecular modeling of clinically relevant variants of the SARS-CoV-2 main protease date: 2020-05-15 words: 3668.0 sentences: 196.0 pages: flesch: 50.0 cache: ./cache/cord-302146-51hof7it.txt txt: ./txt/cord-302146-51hof7it.txt summary: Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mpro variants, constituting all clinically observed mutations in this protein as of April 29, 2020. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery. Molecular modeling is an important tool for guiding inhibitor discovery, making it possible to evaluate large numbers of candidate drugs in silico to select experimental targets; however, standard approaches screen against only one version of the protein, typically the reference or wild-type (WT) sequence. Here we characterize all 79 known variants of M pro as of 29 April, 2020, and analyze trends in amino acid substitutions and the resulting structural changes using network analysis and molecular modeling. Analysis of active site networks (ASN) from M pro variants suggests differences in active site flexibility and cohesion that may serve to guide the design of robust, mutation-resistant inhibitors. abstract: The SARS-CoV-2 main protease (Mpro) is essential to viral replication and cleaves highly specific substrate sequences, making it an obvious target for inhibitor design. However, as for any virus, SARS-CoV-2 is subject to constant selection pressure, with new Mpro mutations arising over time. Identification and structural characterization of Mpro variants is thus critical for robust inhibitor design. Here we report sequence analysis, structure predictions, and molecular modeling for seventy-nine Mpro variants, constituting all clinically observed mutations in this protein as of April 29, 2020. Residue substitution is widely distributed, with some tendency toward larger and more hydrophobic residues. Modeling and protein structure network analysis suggest differences in cohesion and active site flexibility, revealing patterns in viral evolution that have relevance for drug discovery. url: https://doi.org/10.1101/2020.05.15.097493 doi: 10.1101/2020.05.15.097493 id: cord-317628-1inxq7t5 author: Cuccarese, Michael F. title: Functional immune mapping with deep-learning enabled phenomics applied to immunomodulatory and COVID-19 drug discovery date: 2020-08-14 words: 9573.0 sentences: 487.0 pages: flesch: 43.0 cache: ./cache/cord-317628-1inxq7t5.txt txt: ./txt/cord-317628-1inxq7t5.txt summary: We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. We used these capabilities to rapidly develop high-throughput-ready disease models for both SARS-CoV-2 viral infection and the resulting cytokine storm, and immediately launched large-scale drug screens that recapitulated known effective and ineffective therapies and, more importantly, identified several new potential treatments for both SARS-CoV-2 infection and COVID-19-associated cytokine storm. To define the model, we evaluated the effect of SARS-CoV-2 infection in multiple cell types, of which three resulted in robust phenoprints as compared to either mock infected or inactivated virus control populations: Calu3 (a lung adenocarcinoma line), Vero (an immortalized interferondeficient African green monkey kidney line 55 ), and primary Human Renal Cortical Epithelium (HRCE) (Fig. 5C, Fig. S6D ). abstract: Development of accurate disease models and discovery of immune-modulating drugs is challenged by the immune system’s highly interconnected and context-dependent nature. Here we apply deep-learning-driven analysis of cellular morphology to develop a scalable “phenomics” platform and demonstrate its ability to identify dose-dependent, high-dimensional relationships among and between immunomodulators, toxins, pathogens, genetic perturbations, and small and large molecules at scale. High-throughput screening on this platform demonstrates rapid identification and triage of hits for TGF-β- and TNF-α-driven phenotypes. We deploy the platform to develop phenotypic models of active SARS-CoV-2 infection and of COVID-19-associated cytokine storm, surfacing compounds with demonstrated clinical benefit and identifying several new candidates for drug repurposing. The presented library of images, deep learning features, and compound screening data from immune profiling and COVID-19 screens serves as a deep resource for immune biology and cellular-model drug discovery with immediate impact on the COVID-19 pandemic. url: https://doi.org/10.1101/2020.08.02.233064 doi: 10.1101/2020.08.02.233064 id: cord-303832-1kcqhgjw author: Dai, Manman title: Long-term survival of salmon-attached SARS-CoV-2 at 4°C as a potential source of transmission in seafood markets date: 2020-09-06 words: 834.0 sentences: 49.0 pages: flesch: 66.0 cache: ./cache/cord-303832-1kcqhgjw.txt txt: ./txt/cord-303832-1kcqhgjw.txt summary: Several outbreaks of COVID-19 were associated with seafood markets, raising concerns that fish-attached SARS-CoV-2 may exhibit prolonged survival in low-temperature environments. ABSTRACT 21 Several outbreaks of COVID-19 were associated with seafood markets, raising concerns that 22 fish-attached SARS-CoV-2 may exhibit prolonged survival in low-temperature environments. In this study, we detected the titer (50% tissue culture infectious dose/mL, TCID 50 /mL) of 35 viable SARS-CoV-2 attached on salmon or untreated SARS-CoV-2 in culture medium stored at 36 4°C, the temperature in refrigerators or cold rooms for the temporary storage of fish, or 25°C, the 37 regular room temperature, respectively, using end-point titration assay on Vero E6 cells as 38 described previously (8). As shown in Figure A and B, salmon-attached SARS-CoV-2 remained 39 viable at 4°C and 25°C for 8 and 2 days, respectively, while the untreated SARS-CoV-2 in 40 culture medium remained infectious at 4°C and 25°C for more than 8 days. abstract: Several outbreaks of COVID-19 were associated with seafood markets, raising concerns that fish-attached SARS-CoV-2 may exhibit prolonged survival in low-temperature environments. Here we showed that salmon-attached SARS-CoV-2 at 4°C could remain infectious for more than one week, suggesting that fish-attached SARS-CoV-2 may be a source of transmission. url: https://doi.org/10.1101/2020.09.06.284695 doi: 10.1101/2020.09.06.284695 id: cord-102613-hly07ne3 author: Danko, David title: Global Genetic Cartography of Urban Metagenomes and Anti-Microbial Resistance date: 2020-05-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Although studies have shown that urban environments and mass-transit systems have distinct genetic profiles, there are no systematic worldwide studies of these dense, human microbial ecosystems. To address this gap in knowledge, we created a global metagenomic and antimicrobial resistance (AMR) atlas of urban mass transit systems from 60 cities, spanning 4,728 samples and 4,424 taxonomically-defined microorganisms collected for three years. This atlas provides an annotated, geospatial profile of microbial strains, functional characteristics, antimicrobial resistance markers, and novel genetic elements, including 10,928 novel predicted viral species, 1302 novel bacteria, and 2 novel archaea. Urban microbiomes often resemble human commensal microbiomes from the skin and airways, but also contain a consistent “core” of 31 species which are predominantly not human commensal species. Samples show distinct microbial signatures which may be used to accurately predict properties of their city of origin including population, proximity to the coast, and taxonomic profile. These data also show that AMR density across cities varies by several orders of magnitude, including many AMRs present on plasmids with cosmopolitan distributions. Together, these results constitute a high-resolution, global metagenomic atlas, which enables the discovery of new genetic components of the built human environment, highlights potential forensic applications, and provides an essential first draft of the global AMR burden of the world’s cities. url: https://doi.org/10.1101/724526 doi: 10.1101/724526 id: cord-104109-k36jya0b author: Das Jana, Indrani title: Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus date: 2020-09-02 words: 1765.0 sentences: 116.0 pages: flesch: 49.0 cache: ./cache/cord-104109-k36jya0b.txt txt: ./txt/cord-104109-k36jya0b.txt summary: title: Development of a copper-graphene nanocomposite based transparent coating with antiviral activity against influenza virus In this work, we have screened a series of nanoparticles and their composites for antiviral activity using Nano Luciferase based highly sensitive influenza A reporter virus. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide embedded graphene sheet architecture that can inactivate the virion particles only within 30 minutes of pre-incubation and subsequently interferes with the entry of these virion particles into the host cell. This data 142 suggests that the Nano-luciferase influenza A reporter virus could serve as an excellent tool to study the 143 antiviral activity of various nanoparticles or their nanocomposites used in this study. Briefly, Nano-luciferase influenza A reporter viruses were pre-incubated with the 5uM colloidal 146 suspensions of each of the nanoparticles/ composites or with the vehicle control for 30 minutes at room 147 temperature and subsequently used to infect MDCK cells at an MOI of 0.1. abstract: Respiratory infections by RNA viruses are one of the major burdens upon global health and economy. Viruses like influenza or coronaviruses can be transmitted through respiratory droplets or contaminated surfaces. An effective antiviral coating can decrease the viability of the virus particles in the outside environment significantly, hence reducing their transmission rate. In this work, we have screened a series of nanoparticles and their composites for antiviral activity using Nano Luciferase based highly sensitive influenza A reporter virus. Using this screening system, we have identified copper-graphene (Cu-Gr) nanocomposite shows strong antiviral activity. Extensive material and biological characterization of the nanocomposite suggested a unique metal oxide embedded graphene sheet architecture that can inactivate the virion particles only within 30 minutes of pre-incubation and subsequently interferes with the entry of these virion particles into the host cell. This ultimately results in reduced viral gene expression, replication and production of progeny virus particles, slowing down the overall pace of progression of infection. Using PVA as a capping agent, we have been able to generate a Cu-Gr nanocomposite based highly transparent coating that retains its original antiviral activity in the solid form. url: https://doi.org/10.1101/2020.09.02.279737 doi: 10.1101/2020.09.02.279737 id: cord-259340-1ir19s25 author: Das, Rohit Pritam title: Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach date: 2020-07-01 words: 1640.0 sentences: 128.0 pages: flesch: 51.0 cache: ./cache/cord-259340-1ir19s25.txt txt: ./txt/cord-259340-1ir19s25.txt summary: Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The B-cell epitopic regions present in SARS-CoV-2 S protein were identified using BcePred prediction server (https://webs.iiitd.edu.in/cgibin/bcepred/) [17] . Molecular docking was performed between the predicted peptides and MHC representative structures using PatchDock web server [22, 23, 24] . Interaction of both TLR2 and TLR4 structures with the predicted peptides were performed using PatchDock web server [22, 23, 24] . This study is focused on the prediction of effective epitopes from Spike protein of SARS-CoV-2. abstract: Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19. url: https://doi.org/10.1101/2020.07.01.150805 doi: 10.1101/2020.07.01.150805 id: cord-262485-sx2q5ol4 author: Davda, Jayeshkumar Narsibhai title: An Inexpensive RT-PCR Endpoint Diagnostic Assay for SARS-CoV-2 Using Nested PCR: Direct Assessment of Detection Efficiency of RT-qPCR Tests and Suitability for Surveillance date: 2020-06-08 words: 3255.0 sentences: 193.0 pages: flesch: 59.0 cache: ./cache/cord-262485-sx2q5ol4.txt txt: ./txt/cord-262485-sx2q5ol4.txt summary: The method employs real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) of RNA extracted from nasopharyngeal (NP) swab samples, to measure amplification of a short segment of a viral gene in the course of a PCR reaction following reverse transcription of viral RNA. We developed and tested a RT-nPCR protocol comprising a multiplex primary RT-PCR for amplification of four SARS-CoV-2 amplicons and a control human RPP30 amplicon followed by a secondary nested PCR for individual amplicons 4 and visualization by agarose gel electrophoresis. Based on the experimentally measured false negative rate by RT-nPCR tests from this study we estimated that as many as 50% of positive samples may escape detection in single pass testing by RT-qPCR in an actual testing scenario. To detect the presence of SARS-CoV-2 in RNA isolated from NP swabs we performed a multiplex one-step RT-PCR on RNA from positive and negative samples using pooled primers for the four viral amplicons together with human RPP30 control. abstract: With a view to extending testing capabilities for the ongoing SARS-CoV-2 pandemic we have developed a test that lowers cost and does not require real time quantitative reverse transcription polymerase chain reaction (RT-qPCR). We developed a reverse transcription nested PCR endpoint assay (RT-nPCR) and showed that RT-nPCR has comparable performance to the standard RT-qPCR test. In the course of comparing the results of both tests, we found that the standard RT-qPCR test can have low detection efficiency (less than 50%) in a real testing scenario which may be only partly explained by low viral representation in many samples. This finding points to the importance of directly monitoring detection efficiency in test environments. We also suggest measures that would improve detection efficiency. url: https://doi.org/10.1101/2020.06.08.139477 doi: 10.1101/2020.06.08.139477 id: cord-103554-11avjsqu author: Davies, Jennifer L title: Using transcranial magnetic stimulation to map the cortical representation of lower-limb muscles date: 2019-10-17 words: 5335.0 sentences: 288.0 pages: flesch: 56.0 cache: ./cache/cord-103554-11avjsqu.txt txt: ./txt/cord-103554-11avjsqu.txt summary: The aim of this study was to evaluate the extent to which transcranial magnetic stimulation (TMS) can identify discrete cortical representation of lower-limb muscles in healthy individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil could not reliably identify discrete cortical representations of resting lower-limb muscles when responses were measured using bipolar surface electromyography. Cortical representation was 4 mapped for seven resting lower-limb muscles involved in control of the knee joint (rectus femoris, vastus lateralis, vastus medialis, medial hamstring, lateral hamstring, medial gastrocnemius, and lateral gastrocnemius) and was quantified using size, CoG, hotspot and number of discrete peaks. The current results indicate bipolar surface EMG used with TMS delivered through a doublecone coil cannot reliably identify discrete cortical representation of lower-limb muscles in young, healthy individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil cannot reliably identify discrete cortical representations of resting lower-limb muscles when MEPs are measured using bipolar surface EMG. abstract: The aim of this study was to evaluate the extent to which transcranial magnetic stimulation (TMS) can identify discrete cortical representation of lower-limb muscles in healthy individuals. Data were obtained from 16 young healthy adults (12 women, four men; mean [SD] age 23.0 [2.6] years). Motor evoked potentials were recorded from the resting vastus medialis, rectus femoris, vastus lateralis, medial and lateral hamstring, and medial and lateral gastrocnemius muscles on the right side of the body using bipolar surface electrodes. TMS was delivered through a 110-mm double-cone coil at 63 sites over the left hemisphere. Location and size of the cortical representation and the number of discrete peaks were quantified for each muscle. Within the quadriceps muscle group there was a main effect of muscle on anterior-posterior centre of gravity (p = 0.010), but the magnitude of the difference was very small. Within the quadriceps there was a main effect of muscle on medial-lateral hotspot (p = 0.027) and map volume (p = 0.047), but no post-hoc tests were significant. The topography of each lower-limb muscle was complex, displaying multiple peaks that were present across the stimulation grid, and variable across individuals. The results of this study indicate that TMS delivered with a 110-mm double-cone coil could not reliably identify discrete cortical representations of resting lower-limb muscles when responses were measured using bipolar surface electromyography. The characteristics of the cortical representation of lower-limb muscles reported here provide a basis against which to evaluate cortical reorganisation in clinical populations. url: https://doi.org/10.1101/807339 doi: 10.1101/807339 id: cord-102336-ex3zlq38 author: De Wijngaert, Brent title: Cryo-EM structures reveal transcription initiation steps by yeast mitochondrial RNA polymerase date: 2020-04-14 words: 2266.0 sentences: 127.0 pages: flesch: 60.0 cache: ./cache/cord-102336-ex3zlq38.txt txt: ./txt/cord-102336-ex3zlq38.txt summary: Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Hence, the structural basis for promoter melting, DNA scrunching, and transcription initiation remains largely unknown for the mtRNAPs. RPO41 (∆N100) and MTF1 were assembled on a pre-melted promoter (-21 to +12, 15S yeast mtDNA promoter; Fig. 1A ) to generate the yeast mitochondrial transcription preinitiation complex (y-mtPIC) (Fig. S1 ). The 3.7 Å density map of IC locates many previously uncharacterized structural elements, including the C-tail of MTF1 and the scrunched DNA ( Fig. 2B-C) , and reveals the mechanism of template alignment and RNA synthesis during initiation. During the transition, the upstream DNA from position -1 onward is locked in the MTF1 NT-groove while the template strand undergoes a large conformational switching to align with the 2-mer RNA and the incoming UTPaS at the active site ( Fig. 2C; Movie S2). abstract: Cryo-EM structures of transcription pre-initiation complex (PIC) and initiation complex (IC) of yeast mitochondrial RNA polymerase show fully resolved transcription bubbles and explain promoter melting, template alignment, DNA scrunching, transition into elongation, and abortive synthesis. Promoter melting initiates in PIC with MTF1 trapping the −4 to −2 non-template (NT) bases in its NT-groove. Transition to IC is marked by a large-scale movement that aligns the template with RNA at the active site. RNA synthesis scrunches the NT strand into an NT-loop, which interacts with centrally positioned MTF1 C-tail. Steric clashes of the C-tail with RNA:DNA and NT-loop, and dynamic scrunching-unscrunching of DNA explain abortive synthesis and transition into elongation. Capturing the catalytically active IC-state with UTPαS poised for incorporation enables modeling toxicity of antiviral nucleosides/nucleotides. url: https://doi.org/10.1101/2020.04.13.038620 doi: 10.1101/2020.04.13.038620 id: cord-302733-rfuyd041 author: Dellicour, Simon title: A phylodynamic workflow to rapidly gain insights into the dispersal history and dynamics of SARS-CoV-2 lineages date: 2020-10-21 words: 3727.0 sentences: 165.0 pages: flesch: 41.0 cache: ./cache/cord-302733-rfuyd041.txt txt: ./txt/cord-302733-rfuyd041.txt summary: At the country scale, our spatially-explicit phylogeographic analyses highlight that the national lockdown had a relatively low impact on both the lineage dispersal velocity and the long-distance dispersal events within Belgium. At the country scale, our spatially-explicit phylogeographic analyses highlight that the national lockdown had a relatively low impact on both the lineage dispersal velocity and the long-distance dispersal events within Belgium. We generated a time-scaled phylogenetic tree using a rapid maximum likelihood approach 16 and subsequently ran a preliminary discrete phylogeographic analysis along this tree to identify internal nodes and descending clades that likely correspond to distinct introductions into the Belgian territory ( Fig. 1, S2 ). We used the continuous diffusion model 13 available in BEAST 1.10 14 to perform a spatially-explicit (or "continuous") phylogeographic reconstruction of the dispersal history of SARS-CoV-2 lineages in Belgium. abstract: Since the start of the COVID-19 pandemic, an unprecedented number of genomic sequences of the causative virus (SARS-CoV-2) have been generated and shared with the scientific community. The unparalleled volume of available genetic data presents a unique opportunity to gain real-time insights into the virus transmission during the pandemic, but also a daunting computational hurdle if analysed with gold-standard phylogeographic approaches. We here describe and apply an analytical pipeline that is a compromise between fast and rigorous analytical steps. As a proof of concept, we focus on the Belgium epidemic, with one of the highest spatial density of available SARS-CoV-2 genomes. At the global scale, our analyses confirm the importance of external introduction events in establishing multiple transmission chains in the country. At the country scale, our spatially-explicit phylogeographic analyses highlight that the national lockdown had a relatively low impact on both the lineage dispersal velocity and the long-distance dispersal events within Belgium. Our pipeline has the potential to be quickly applied to other countries or regions, with key benefits in complementing epidemiological analyses in assessing the impact of intervention measures or their progressive easement. url: https://doi.org/10.1101/2020.05.05.078758 doi: 10.1101/2020.05.05.078758 id: cord-102968-mhawyect author: Desirò, Daniel title: SilentMutations (SIM): a tool for analyzing long-range RNA-RNA interactions in viral genomes and structural RNAs date: 2018-09-23 words: 4044.0 sentences: 233.0 pages: flesch: 58.0 cache: ./cache/cord-102968-mhawyect.txt txt: ./txt/cord-102968-mhawyect.txt summary: Results Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate destructive and compensatory mutants of two interacting single-stranded RNAs. This will facilitate a fast and accurate assessment of key regions, possibly involved in functional long-range RNA-RNA interactions and finally help virologists to design appropriate experiments. In this study, we present a tool called SilentMutations (SIM) that effectively simulates synonymous (silent) compensatory mutations in two single-stranded viral RNAs and is therefore appropriate for the in vitro assessment of predicted LRIs. Here, we present a command-line tool, called SilentMutations (SIM), that can simulate synonymous structure-destroying and structurepreserving mutation pairs within coding regions for long-range RNA-RNA interaction experiments. Figure 1 : Overall workflow of the SilentMutations tool, exemplary shown for two sequences from a negative single-stranded RNA virus genome (ssRNA-) (a) The first step will extract the defined range in each sequence and possibly increase the range to preserve codons in the given reading frame. abstract: Background A single nucleotide change or mutation in the coding region can alter the amino acid sequence of a protein. In consequence, natural or artificial sequence changes in viral RNAs may have various effects not only on protein stability, function and structure but also on viral replication. In the last decade, several tools have been developed to predict the effect of mutations in structural RNA genomes. Some tools employ multiple point mutations and are also taking coding regions into account. However, none of these tools was designed to specifically simulate the effect of mutations on viral long-range interactions. Results Here, we developed SilentMutations (SIM), an easy-to-use tool to analyze the effect of multiple point mutations on the secondary structures of two interacting viral RNAs. The tool can simulate destructive and compensatory mutants of two interacting single-stranded RNAs. This will facilitate a fast and accurate assessment of key regions, possibly involved in functional long-range RNA-RNA interactions and finally help virologists to design appropriate experiments. SIM only needs two interacting single-stranded RNA regions as input. The output is a plain text file containing the most promising mutants and a graphical representation of all interactions. Conclusion We applied our tool on two experimentally validated influenza A virus and hepatitis C virus interactions and we were able to predict potential double mutants for in vitro validation experiments. Availability The source code and documentation of SIM are freely available at github.com/desiro/SilentMutations url: https://doi.org/10.1101/424002 doi: 10.1101/424002 id: cord-268224-5tbb8df1 author: Di Gioacchino, Andrea title: The heterogeneous landscape and early evolution of pathogen-associated CpG dinucleotides in SARS-CoV-2 date: 2020-08-27 words: 7109.0 sentences: 412.0 pages: flesch: 62.0 cache: ./cache/cord-268224-5tbb8df1.txt txt: ./txt/cord-268224-5tbb8df1.txt summary: Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven, in the N protein coding region, both by the viral codon bias and by the high value of the CpG content, leading to a loss in CpG. Finally we use a model of the viral gene evolution under human host pressure, characterized by the CpG force, to study synonymous mutations, and in particular those which change CpG content, observed since the SARS-CoV-2 entered the human population (Sec. 2.3). We first compute the global force on CpG dinucleotides for SARS-Cov-2 and a variety of other viruses from the Coronaviridae family affecting humans or other mammals (bat, pangolin), see Fig. 1a , using as null model the nucleotide usage calculated from human genome [22] (see Methods Sec. 4.2) 1 . abstract: COVID-19 can lead to acute respiratory syndrome in patients, which can be due to dysregulated immune signaling. We analyze the distribution of CpG dinucleotides, a pathogen-associated molecular pattern, in the SARS-CoV-2 genome. We find that CpG relative abundance, which we characterize by an adequate force parameter taking into account statistical constraints acting on the genome at the nucleotidic and amino-acid levels is, on the overall, low compared to other pathogenic betacoronaviruses. However, the CpG force widely fluctuates along the genome, with particularly low value, comparable to the circulating seasonal HKU1, in the Spike protein (S) coding region and high value, comparable to SARS and MERS, in the highly expressed nucleocapside (N) coding regions, whose transcripts are relatively abundant in the cytoplasm of infected cells and present in the 3’UTRs of all subgenomic RNA. This dual nature of CpG content could confer to SARS-CoV-2 the ability to avoid triggering pattern recognition receptors upon entry, while eliciting a stronger response during replication. We then investigate the evolution of synonymous mutations since the outbreak of the COVID-19 pandemic. Using a model of the viral gene evolution under human host pressure, we find that synonymous mutations seem driven, in the N protein coding region, both by the viral codon bias and by the high value of the CpG content, leading to a loss in CpG. Sequence motifs preceding these CpG-loss-associated loci match recently identified binding patterns of the Zinc finger Anti-viral Protein. url: https://www.ncbi.nlm.nih.gov/pubmed/32511407/ doi: 10.1101/2020.05.06.074039 id: cord-262726-lfuxhlki author: Diallo, Aïssatou Bailo title: Daytime variation in SARS-CoV-2 infection and cytokine production date: 2020-09-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: S. Ray and A. Reddy recently anticipated the implication of circadian rhythm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of the coronavirus disease (Covid-19). In addition to its key role in the regulation of biological functions, the circadian rhythm has been suggested as a regulator of viral infections. Specifically, the time of day of infection was found critical for illness progression, as has been reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. We analyzed circadian rhythm implication in SARS-CoV-2 virus infection of isolated human monocytes, key actor cells in Covid-19 disease, from healthy subjects. The circadian gene expression of Bmal1 and Clock genes was investigated with q-RTPCR. Monocytes were infected with SARS-CoV-2 virus strain and viral infection was investigated by One-Step qRT-PCR and immunofluorescence. Interleukin (IL)-6, IL-1β and IL-10 levels were also measured in supernatants of infected monocytes. Using Cosinor analysis, we showed that Bmal1 and Clock transcripts exhibited circadian rhythm in monocytes with an acrophase and a bathyphase at Zeitgeber Time (ZT)6 and ZT17. After forty-eight hours, the amount of SARS-CoV-2 virus increased in the monocyte infected at ZT6 compared to ZT17. The high virus amount at ZT6 was associated with significant increased release in IL-6, IL-1β and IL-10 compared to ZT17. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression. Importance The implication of circadian rhythm (CR) in pathogenesis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been recently anticipated. The time of day of infection is critical for illness progression as reported for influenza, respiratory syncytial and parainfluenza type 3 viruses. In this study, we wondered if SARS-CoV-2 infection and cytokine production by human monocytes, innate immune cells affected by Covid-19, were regulated by CR. Our results suggest that time day of SARS-CoV-2 infection affects viral infection and host immune response. They support consideration of circadian rhythm in SARS-CoV-2 disease progression and we propose circadian rhythm as a novel target for managing viral progression. url: https://doi.org/10.1101/2020.09.09.290718 doi: 10.1101/2020.09.09.290718 id: cord-331786-wgt7kg6f author: Diego-Martin, Borja title: Pilot production of SARS-CoV-2 related proteins in plants: a proof of concept for rapid repurposing of indoors farms into biomanufacturing facilities date: 2020-10-13 words: 7034.0 sentences: 326.0 pages: flesch: 45.0 cache: ./cache/cord-331786-wgt7kg6f.txt txt: ./txt/cord-331786-wgt7kg6f.txt summary: For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. In parallel, we also produced the recombinant SARS-CoV-2 N protein and its Receptor Binding Domain (RBD) in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Finally, we performed sandwich ELISA tests of sybody17 and nanobody72 ( Fig 5E and Fig 5F, respectively) using the total and concentrated apoplastic fluid as detection reagent against serial dilutions of crude plant extracts from RBD-producing plants, showing that this simple antibody preparation can be directly employed in detection procedures without the need of additional purification steps. abstract: The current CoVid-19 crisis is revealing the strengths and the weaknesses of the world’s capacity to respond to a global health crisis. A critical weakness has resulted from the excessive centralization of the current biomanufacturing capacities, a matter of great concern, if not a source of nationalistic tensions. On the positive side, scientific data and information have been shared at an unprecedented speed fuelled by the preprint phenomena, and this has considerably strengthened our ability to develop new technology-based solutions. In this work we explore how, in a context of rapid exchange of scientific information, plant biofactories can serve as a rapid and easily adaptable solution for local manufacturing of bioreagents, more specifically recombinant antibodies. For this purpose, we tested our ability to produce, in the framework of an academic lab and in a matter of weeks, milligram amounts of six different recombinant monoclonal antibodies against SARS-CoV-2 in Nicotiana benthamiana. For the design of the antibodies we took advantage, among other data sources, of the DNA sequence information made rapidly available by other groups in preprint publications. mAbs were all engineered as single-chain fragments fused to a human gamma Fc and transiently expressed using a viral vector. In parallel, we also produced the recombinant SARS-CoV-2 N protein and its Receptor Binding Domain (RBD) in planta and used them to test the binding specificity of the recombinant mAbs. Finally, for two of the antibodies we assayed a simple scale-up production protocol based on the extraction of apoplastic fluid. Our results indicate that gram amounts of anti-SARS-CoV-2 antibodies could be easily produced in little more than 6 weeks in repurposed greenhouses with little infrastructure requirements using N. benthamiana as production platform. Similar procedures could be easily deployed to produce diagnostic reagents and, eventually, could be adapted for rapid therapeutic responses. url: https://doi.org/10.1101/2020.10.13.331306 doi: 10.1101/2020.10.13.331306 id: cord-281717-kzd9vvci author: Digard, Paul title: Intra-genome variability in the dinucleotide composition of SARS-CoV-2 date: 2020-05-08 words: 4473.0 sentences: 266.0 pages: flesch: 53.0 cache: ./cache/cord-281717-kzd9vvci.txt txt: ./txt/cord-281717-kzd9vvci.txt summary: CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. CpG suppression amongst coronaviruses does not significantly differ according to genera of virus, but does vary according to host species and primary replication site (a proxy for tissue tropism), supporting the hypothesis that viral CpG content may influence cross-species transmission. 79 SARS-CoV-2 was recently reported to have a CpG composition lower than other members of the 80 betacoronavirus genus, comparable to certain canine alphacoronaviruses; an observation used to draw 81 inferences over its origin and/or epizootic potential (Xia 2020 in GC content (from ~ 0.32 -0.47) was seen across the Coronaviridae, and as expected, all viruses 97 exhibited some degree of CpG suppression, with CpG O:E ratios ranging from 0.37 to 0.74 (Fig 2A) . abstract: CpG dinucleotides are under-represented in the genomes of single stranded RNA viruses, and coronaviruses, including SARS-CoV-2, are no exception to this. Artificial modification of CpG frequency is a valid approach for live attenuated vaccine development, and if this is to be applied to SARS-CoV-2, we must first understand the role CpG motifs play in regulating SARS-CoV-2 replication. Accordingly, the CpG composition of the newly emerged SARS-CoV-2 genome was characterised in the context of other coronaviruses. CpG suppression amongst coronaviruses does not significantly differ according to genera of virus, but does vary according to host species and primary replication site (a proxy for tissue tropism), supporting the hypothesis that viral CpG content may influence cross-species transmission. Although SARS-CoV-2 exhibits overall strong CpG suppression, this varies considerably across the genome, and the Envelope (E) open reading frame (ORF) and ORF10 demonstrate an absence of CpG suppression. While ORF10 is only present in the genomes of a subset of coronaviruses, E is essential for virus replication. Across the Coronaviridae, E genes display remarkably high variation in CpG composition, with those of SARS and SARS-CoV-2 having much higher CpG content than other coronaviruses isolated from humans. Phylogeny indicates that this is an ancestrally-derived trait reflecting their origin in bats, rather than something selected for after zoonotic transfer. Conservation of CpG motifs in these regions suggests that they have a functionality which over-rides the need to suppress CpG; an observation relevant to future strategies towards a rationally attenuated SARS-CoV-2 vaccine. url: https://doi.org/10.1101/2020.05.08.083816 doi: 10.1101/2020.05.08.083816 id: cord-334584-xh41koro author: Dilucca, Maddalena title: Temporal evolution and adaptation of SARS-COV 2 codon usage date: 2020-05-29 words: 3955.0 sentences: 210.0 pages: flesch: 56.0 cache: ./cache/cord-334584-xh41koro.txt txt: ./txt/cord-334584-xh41koro.txt summary: Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2''-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. An EN C plot analysis was performed to estimate the relative contributions of mutational bias and natural selection in shaping CUB of 13 genes encoding proteins that are crucial for SARS-CoV-2. For the funtionally important genes in each genome, we calculated the average values of CAI and ENC over time, as compared to the reference SARS-CoV-2 sequence (WSM). Based on the SiD combined with the CAI results ( Figure 5 ), we suggest that SARS-CoV-2, over time, has preferentially accumulated mutations in its genome which correspond to codons that adapt better to the human host. abstract: The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2’-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host. url: https://doi.org/10.1101/2020.05.29.123976 doi: 10.1101/2020.05.29.123976 id: cord-267613-hsc2x36j author: Dittmar, Mark title: Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2 date: 2020-06-19 words: 7558.0 sentences: 452.0 pages: flesch: 50.0 cache: ./cache/cord-267613-hsc2x36j.txt txt: ./txt/cord-267613-hsc2x36j.txt summary: Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. Previous studies found that the antiviral drug remdesivir, which was developed against the RNA-dependent RNA polymerase of Ebola virus, was also active against SARS-CoV-2 in vitro, with promising results in clinical trials (5) (6) (7) . Both cepharanthine and tetrandrine were previously shown to have antiviral activity against the human coronavirus OC43 and in recent studies on SARS-CoV-2 in Vero cell screens (13, 62, 63) . Strikingly, the activities of all of these drugs is similar in the two cell lines suggesting the same target and mechanism-of-action and that Cyclosporine would block SARS-CoV-2 in diverse infected tissues in vivo. abstract: There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening in human Huh7.5 cells validated 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we found that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. These antivirals reveal essential host targets and have the potential for rapid clinical implementation. url: https://doi.org/10.1101/2020.06.19.161042 doi: 10.1101/2020.06.19.161042 id: cord-297684-9q3oopaz author: Dobaño, Carlota title: Highly sensitive and specific multiplex antibody assays to quantify immunoglobulins M, A and G against SARS-CoV-2 antigens date: 2020-06-12 words: 5198.0 sentences: 226.0 pages: flesch: 41.0 cache: ./cache/cord-297684-9q3oopaz.txt txt: ./txt/cord-297684-9q3oopaz.txt summary: The Receptor-Binding Domain (RBD) of the spike (S) glycoprotein of SARS-CoV-2, the leading vaccine candidate target, was selected as the primary antigen to develop the initial qSAT assay because (i) S is one of the most immunogenic surface proteins together with the nucleocapsid protein (N) (20) (ii) RBD is the fragment of the virus that mediates binding to the host receptor ACE2 in the lung cells (21) (iii) antibodies to RBD correlate with neutralizing antibodies (20)(22) that could be associated with protection based on studies of other coronaviruses and animal models (23) (24) (25) (26) , and (iv) an ELISA based on this same protein has received FDA approval for COVID-19 serology (11) . We developed three novel multiplex immunoassays for quantifying IgM, IgA and IgG to eight SARS-CoV-2 protein constructs and evaluated by machine learning classification algorithms the performance of several isotype/antigen combinations to detect any positive antibody response to infection, obtaining specificities of 100% and sensitivities of 94.94% (≥14 days since symptoms onset) or 96.08% (≥21 days since symptoms onset), and very high predictability (AUC ≥0.99). abstract: Reliable serological tests are required to determine the prevalence of antibodies against SARS-CoV-2 antigens and to characterise immunity to the disease in order to address key knowledge gaps in the context of the COVID-19 pandemic. Quantitative suspension array technology (qSAT) assays based on the xMAP Luminex platform overcome the limitations of rapid diagnostic tests and ELISA with their higher precision, dynamic range, throughput, miniaturization, cost-efficacy and multiplexing capacity. We developed three qSAT assays to detect IgM, IgA and IgG to a panel of eight SARS-CoV-2 antigens including spike (S), nucleoprotein (N) and membrane (M) protein constructs. The assays were optimized to minimize processing time and maximize signal to noise ratio. We evaluated the performance of the assays using 128 plasmas obtained before the COVID-19 pandemic (negative controls) and 115 plasmas from individuals with SARS-CoV-2 diagnosis (positive controls), of whom 8 were asymptomatic, 58 had mild symptoms and 49 were hospitalized. Pre-existing IgG antibodies recognizing N, M and S2 proteins were detected in negative controls suggestive of cross-reactive to common cold coronaviruses. The best performing antibody isotype/antigen signatures had specificities of 100% and sensitivities of 94.94% at ≥14 days since the onset of symptoms and 96.08% at ≥21 days since the onset of symptoms, with AUC of 0.992 and 0.999, respectively. Combining multiple antibody markers as assessed by qSAT assays has the highest efficiency, breadth and versatility to accurately detect low-level antibody responses for obtaining reliable data on prevalence of exposure to novel pathogens in a population. Our assays will allow gaining insights into antibody correlates of immunity required for vaccine development to combat pandemics like the COVID-19. url: https://doi.org/10.1101/2020.06.11.147363 doi: 10.1101/2020.06.11.147363 id: cord-103417-2uinislh author: Doi, Hideyuki title: On-site eDNA detection of species using ultra-rapid mobile PCR date: 2020-10-01 words: 1507.0 sentences: 91.0 pages: flesch: 50.0 cache: ./cache/cord-103417-2uinislh.txt txt: ./txt/cord-103417-2uinislh.txt summary: Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Ultra-rapid methods from DNA collection to detection are still not well developed (1), especially for environmental DNA (eDNA) analysis, which uses water or soil samples to track the presence of target species (2, 3) . Here, we developed a new innovative method for the field processing of eDNA samples and measurements using an ultra-rapid mobile PCR platform (hereafter, mobile PCR) to reduce the measurement time to 30 min and maintain high detectability of aquatic organisms. We compared the on-site eDNA measurement to the laboratory extraction and detection using a benchtop qPCR platform and the national survey to confirm the performance. Our ultra-rapid on-site eDNA extraction and measurement method using mobile PCR successfully detected the eDNA of H. abstract: Molecular methods, including environmental DNA (eDNA) methods, provide essential information for biological and conservation sciences. Molecular measurements are often performed in the laboratory, which limits their scope, especially for rapid on-site analysis. eDNA methods for species detection provide essential information for the management and conservation of species and communities in various environments. We developed an innovative novel method for on-site eDNA measurements using an ultra-rapid mobile PCR platform. We tested the ability of our method to detect the distribution of silver carp, Hypophthalmichthys molitrix, an invasive fish in Japanese rivers and lakes. Our method reduced the measurement time to 30 min and provided high detectability of aquatic organisms compared to the national observation surveys using multiple fishing nets and laboratory extraction/detection using a benchtop qPCR platform. Our on-site eDNA method can be immediately applied to various taxa and environments. url: https://doi.org/10.1101/2020.09.28.314625 doi: 10.1101/2020.09.28.314625 id: cord-266444-rw94yls8 author: Dominguez Andres, Ana title: SARS-CoV-2 ORF9c Is a Membrane-Associated Protein that Suppresses Antiviral Responses in Cells date: 2020-08-19 words: 5639.0 sentences: 305.0 pages: flesch: 44.0 cache: ./cache/cord-266444-rw94yls8.txt txt: ./txt/cord-266444-rw94yls8.txt summary: The interactome and proteome studies identified cellular processes affected by SARS-CoV-2 infection or specific viral proteins, notably innate immune signaling (19, 20, 23, (28) (29) (30) , ubiquitin ligase activities (19, 20, 23, (28) (29) (30) , p38 mitogenactivated protein kinase (MAPK) signaling (19, 20, 23, (28) (29) (30) . To assess if there were notable differences in the intensity of the changes in protein abundance in response to proteasome inhibition, we calculated relative changes in protein abundance between control and ORF9c-expressing cells from both the DMSO and MG132 conditions for proteins associated with IFN signaling or the ubiquitin proteasome (UBP) system and antigen presentation (Fig. 2D ). In contrast to the proteomic results that revealed predominant downregulation of proteins following ORF9c expression, RNA-seq analysis showed a similar number of transcripts were increased or decreased in the presence or absence of MG132 (Fig. 3A, table S2 ). abstract: Disrupted antiviral immune responses are associated with severe COVID-19, the disease caused by SAR-CoV-2. Here, we show that the 73-amino-acid protein encoded by ORF9c of the viral genome contains a putative transmembrane domain, interacts with membrane proteins in multiple cellular compartments, and impairs antiviral processes in a lung epithelial cell line. Proteomic, interactome, and transcriptomic analyses, combined with bioinformatic analysis, revealed that expression of only this highly unstable small viral protein impaired interferon signaling, antigen presentation, and complement signaling, while inducing IL-6 signaling. Furthermore, we showed that interfering with ORF9c degradation by either proteasome inhibition or inhibition of the ATPase VCP blunted the effects of ORF9c. Our study indicated that ORF9c enables immune evasion and coordinates cellular changes essential for the SARS-CoV-2 life cycle. One-sentence summary SARS-CoV-2 ORF9c is the first human coronavirus protein localized to membrane, suppressing antiviral response, resembling full viral infection. url: https://doi.org/10.1101/2020.08.18.256776 doi: 10.1101/2020.08.18.256776 id: cord-346546-yffwd0dc author: Douangamath, Alice title: Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease date: 2020-05-27 words: 4059.0 sentences: 259.0 pages: flesch: 56.0 cache: ./cache/cord-346546-yffwd0dc.txt txt: ./txt/cord-346546-yffwd0dc.txt summary: To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease. For 113 another series of hit compounds, containing a N-chloroacetyl piperidinyl-4-carboxamide 114 motif (Table S2 ) which displays lower reactivity and were not frequent hitters in previous 115 screens, we attempted crystallization despite their absence of labelling in the stringent 116 The bound fragments comprehensively sample all subsites of the active 287 site revealing diverse expansion vectors, and the electrophiles provide extensive, systematic 288 as well as serendipitous, data for designing covalent compounds. Crystal structure of SARS-CoV-2 main protease 763 provides a basis for design of improved alpha-ketoamide inhibitors abstract: COVID-19, caused by SARS-CoV-2, lacks effective therapeutics. Additionally, no antiviral drugs or vaccines were developed against the closely related coronavirus, SARS-CoV-1 or MERS-CoV, despite previous zoonotic outbreaks. To identify starting points for such therapeutics, we performed a large-scale screen of electrophile and non-covalent fragments through a combined mass spectrometry and X-ray approach against the SARS-CoV-2 main protease, one of two cysteine viral proteases essential for viral replication. Our crystallographic screen identified 71 hits that span the entire active site, as well as 3 hits at the dimer interface. These structures reveal routes to rapidly develop more potent inhibitors through merging of covalent and non-covalent fragment hits; one series of low-reactivity, tractable covalent fragments was progressed to discover improved binders. These combined hits offer unprecedented structural and reactivity information for on-going structure-based drug design against SARS-CoV-2 main protease. url: https://doi.org/10.1101/2020.05.27.118117 doi: 10.1101/2020.05.27.118117 id: cord-350935-p6euuop3 author: Doğan, Tunca title: CROssBAR: Comprehensive Resource of Biomedical Relations with Deep Learning Applications and Knowledge Graph Representations date: 2020-09-15 words: 7066.0 sentences: 298.0 pages: flesch: 45.0 cache: ./cache/cord-350935-p6euuop3.txt txt: ./txt/cord-350935-p6euuop3.txt summary: We aimed to address this issue by constructing a new biological and biomedical data resource, CROssBAR, a comprehensive system that integrates large-scale biomedical data from various resources and store them in a new NoSQL database, enrich these data with deep-learning-based prediction of relations between numerous biomedical entities, rigorously analyse the enriched data to obtain biologically meaningful modules and display them to users via easy-to-interpret, interactive and heterogenous knowledge graph (KG) representations within an open access, user-friendly and online web-service at https://crossbar.kansil.org. In this project, we aimed to address the current shortcomings by developing a comprehensive open access biomedical system entitled CROssBAR via integrating various biological databases to each other, inferring the missing relations between existing data points, and constructing informative knowledge graphs based on specific biomedical components/terms such as a disease/phenotype, biological process, gene/protein and drug/compound, or specific combinations of them. abstract: Systemic analysis of available large-scale biological and biomedical data is critical for developing novel and effective treatment approaches against both complex and infectious diseases. Owing to the fact that different sections of the biomedical data is produced by different organizations/institutions using various types of technologies, the data are scattered across individual computational resources, without any explicit relations/connections to each other, which greatly hinders the comprehensive multi-omics-based analysis of data. We aimed to address this issue by constructing a new biological and biomedical data resource, CROssBAR, a comprehensive system that integrates large-scale biomedical data from various resources and store them in a new NoSQL database, enrich these data with deep-learning-based prediction of relations between numerous biomedical entities, rigorously analyse the enriched data to obtain biologically meaningful modules and display them to users via easy-to-interpret, interactive and heterogenous knowledge graph (KG) representations within an open access, user-friendly and online web-service at https://crossbar.kansil.org. As a use-case study, we constructed CROssBAR COVID-19 KGs (available at: https://crossbar.kansil.org/covid_main.php) that incorporate relevant virus and host genes/proteins, interactions, pathways, phenotypes and other diseases, as well as known and completely new predicted drugs/compounds. Our COVID-19 graphs can be utilized for a systems-level evaluation of relevant virus-host protein interactions, mechanisms, phenotypic implications and potential interventions. url: https://doi.org/10.1101/2020.09.14.296889 doi: 10.1101/2020.09.14.296889 id: cord-343317-97n1j0jj author: Duan, Xiaohua title: Identification of Drugs Blocking SARS-CoV-2 Infection using Human Pluripotent Stem Cell-derived Colonic Organoids date: 2020-05-02 words: 3776.0 sentences: 222.0 pages: flesch: 56.0 cache: ./cache/cord-343317-97n1j0jj.txt txt: ./txt/cord-343317-97n1j0jj.txt summary: Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. The organoids infected with SARS-CoV-2 pseudo-entry virus at MOI=0.01 showed a strong signal at 24 hpi (Fig. 2a) . The mRNAs of SARS-CoV-2 pseudo-entry virus, including VSV-NS, VSV-N, and VSV-M, were detected in all five cell populations (Fig. 2f) , but not in the uninfected COs (Extended Data Fig. 2f) . Immunohistochemistry detected luciferase in ACE2 + and Villin + cells, suggesting these are permissive to SARS-CoV-2 pseudo-entry virus infection in vivo (Fig. 2k) . Next, we adapted hPSC-COs to a high throughput screening platform and probed the Prestwick FDA-approved drug library to identify drug candidates capable of blocking SARS-CoV-2 pseudo-virus infection. abstract: The current COVID-19 pandemic is caused by SARS-coronavirus 2 (SARS-CoV-2). There are currently no therapeutic options for mitigating this disease due to lack of a vaccine and limited knowledge of SARS-CoV-2 biology. As a result, there is an urgent need to create new disease models to study SARS-CoV-2 biology and to screen for therapeutics using human disease-relevant tissues. COVID-19 patients typically present with respiratory symptoms including cough, dyspnea, and respiratory distress, but nearly 25% of patients have gastrointestinal indications including anorexia, diarrhea, vomiting, and abdominal pain. Moreover, these symptoms are associated with worse COVID-19 outcomes1. Here, we report using human pluripotent stem cell-derived colonic organoids (hPSC-COs) to explore the permissiveness of colonic cell types to SARS-CoV-2 infection. Single cell RNA-seq and immunostaining showed that the putative viral entry receptor ACE2 is expressed in multiple hESC-derived colonic cell types, but highly enriched in enterocytes. Multiple cell types in the COs can be infected by a SARS-CoV-2 pseudo-entry virus, which was further validated in vivo using a humanized mouse model. We used hPSC-derived COs in a high throughput platform to screen 1280 FDA-approved drugs against viral infection. Mycophenolic acid and quinacrine dihydrochloride were found to block the infection of SARS-CoV-2 pseudo-entry virus in COs both in vitro and in vivo, and confirmed to block infection of SARS-CoV-2 virus. This study established both in vitro and in vivo organoid models to investigate infection of SARS-CoV-2 disease-relevant human colonic cell types and identified drugs that blocks SARS-CoV-2 infection, suitable for rapid clinical testing. url: https://doi.org/10.1101/2020.05.02.073320 doi: 10.1101/2020.05.02.073320 id: cord-322885-ob5euspo author: Durdagi, Serdar title: Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing date: 2020-09-09 words: 10818.0 sentences: 656.0 pages: flesch: 54.0 cache: ./cache/cord-322885-ob5euspo.txt txt: ./txt/cord-322885-ob5euspo.txt summary: One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19. Radiation-damage-free SFX method which enables obtaining the novel high-resolution ambient-temperature structures of the binding pocket of Mpro provides an unprecedented opportunity for identification of highly effective inhibitors for drug repurposing by using a hybrid approach that combines structural and in silico methods. We determined two radiation-damage-free SFX crystal structures of SARS-CoV-2 Mpro in two crystal forms at 1.9 Å and 2.1 Å resolutions with the following PDB IDs: 7CWB and 7CWC, respectively (Fig. 1A, B) (Supplementary Table 1&2 The diffraction data collected remotely at the MFX instrument of the LCLS at SLAC National Laboratory, Menlo Park, CA (Sierra et al., They reveal novel active site residue conformations and dynamics at atomic level, revealing several differences compared to the prior ambient-temperature structure of SARS-CoV-2 Mpro that was obtained at a home X-ray source (Fig. 1A, B ). abstract: The COVID19 pandemic has resulted in 25+ million reported infections and nearly 850.000 deaths. Research to identify effective therapies for COVID19 includes: i) designing a vaccine as future protection; ii) structure-based drug design; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determined two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 main protease at ambienttemperature by Serial Femtosecond X-ray crystallography. We employed detailed molecular simulations of selected known main protease inhibitors with the structures and compared binding modes and energies. The combined structural biology and molecular modeling studies not only reveal the dynamics of small molecules targeting main protease but will also provide invaluable opportunities for drug repurposing and structure-based drug design studies against SARS-CoV-2. One Sentence Summary Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19. url: https://doi.org/10.1101/2020.09.09.287987 doi: 10.1101/2020.09.09.287987 id: cord-103915-rzy7mejb author: Duricki, Denise A. title: Corticospinal neuroplasticity and sensorimotor recovery in rats treated by infusion of neurotrophin-3 into disabled forelimb muscles started 24 h after stroke date: 2018-07-11 words: 12866.0 sentences: 671.0 pages: flesch: 54.0 cache: ./cache/cord-103915-rzy7mejb.txt txt: ./txt/cord-103915-rzy7mejb.txt summary: We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. We also recently showed that injection of an adeno-associated viral vector (AAV) encoding full-length human NT3 (preproNT3, 30kDa) into forelimb muscles 24 hours after stroke in adult or elderly rats improved sensorimotor recovery 19 . We examined anatomical neuroplasticity in the C7 cervical spinal cord because we knew from experiments using adult and elderly rats that the less-affected corticospinal tract sprouts at this level (as well as other levels) after injection of AAV-NT3 into muscles including triceps brachii 19 . fMRI performed one week after stroke confirmed that somatosensory cortex was not active when the affected paw was stimulated in either vehicle or NT3 treated rats (p>0.05, Supplementary Fig. 6b ). Treatment of disabled arm muscles with NT3 protein, initiated 24 hours after stroke, caused changes in multiple locomotor circuits, and promoted a progressive recovery of sensory and motor function in rats. abstract: Stroke often leads to arm disability and reduced responsiveness to stimuli on the other side of the body. Neurotrophin-3 (NT3) is made by skeletal muscle during infancy but levels drop postnatally and into adulthood. It is essential for the survival and wiring-up of sensory afferents from muscle. We have previously shown that gene therapy delivery of human NT3 into the affected triceps brachii forelimb muscle improves sensorimotor recovery after ischemic stroke in adult and elderly rats. Here, to move this therapy one step nearer to the clinic, we set out to test the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after ischemic cortical stroke in adult rats. To simulate a clinically-feasible time-to-treat, twenty-four hours later rats were randomized to receive NT3 or vehicle by infusion into triceps brachii for four weeks using implanted minipumps. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory deficits on the affected forearm. There was no evidence of forepaw sensitivity to cold stimuli after stroke or NT3 treatment. MRI confirmed that treatment did not induce neuroprotection. Functional MRI during low threshold electrical stimulation of the affected forearm showed an increase in peri-infarct BOLD signal with time in both stroke groups and indicated that neurotrophin-3 did not further increase peri-infarct BOLD signal. Rather, NT3 induced spinal neuroplasticity including sprouting of the spared corticospinal and serotonergic pathways. Neurophysiology showed that NT3 treatment increased functional connectivity between the corticospinal tracts and spinal circuits controlling muscles on the treated side. After intravenous injection, radiolabelled NT3 crossed from bloodstream into the brain and spinal cord in adult mice with or without strokes. Our results show that delayed, peripheral infusion of neurotrophin-3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral, high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke. url: https://doi.org/10.1101/367573 doi: 10.1101/367573 id: cord-296237-i9cti2ok author: Díez, José-María title: Cross-neutralization activity against SARS-CoV-2 is present in currently available intravenous immunoglobulins date: 2020-06-19 words: 3741.0 sentences: 220.0 pages: flesch: 51.0 cache: ./cache/cord-296237-i9cti2ok.txt txt: ./txt/cord-296237-i9cti2ok.txt summary: Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. Recently, cross-reactivity in ELISA binding assays against antigens of SARS-CoV, SARS-CoV-2, and MERS-CoV has been reported with currently available intravenous immunoglobulins (IVIG) such as Gamunex-C and Flebogamma DIF 19 . In this study, the neutralization capacity of the IVIG products Gamunex-C and Flebogamma DIF against these epidemic human coronaviruses -SARS-CoV, SARS-CoV-2, and MERS-CoV-was evaluated. Six different lots of Flebogamma DIF and Gamunex-C were tested at several dilutions for cross-reactivity against SARS-CoV, SARS-CoV-2, and MERS-CoV by: i) ELISA techniques; and ii) well-stablished neutralization assays in cell cultures. For SARS-CoV-2 MAD6 isolate, all IVIG lots, except F1 (inconclusive results) showed a significant neutralizing activity and reached PRNT50 titers ranging from 4.5 to >5 (Figure 2 ). abstract: Background There is a crucial need for effective therapies that are immediately available to counteract COVID-19 disease. Recently, ELISA binding cross-reactivity against components of human epidemic coronaviruses with currently available intravenous immunoglobulins (IVIG) Gamunex-C and Flebogamma DIF (5% and 10%) have been reported. In this study, the same products were tested for neutralization activity against SARS-CoV-2, SARS-CoV and MERS-CoV and their potential as an antiviral therapy. Methods The neutralization capacity of six selected lots of IVIG was assessed against SARS-CoV-2 (two different isolates), SARS-CoV and MERS-CoV in cell cultures. Infectivity neutralization was measured by determining the percent reduction in plaque-forming units (PFU) and by cytopathic effects for two IVIG lots in one of the SARS-CoV-2 isolates. Neutralization was quantified using the plaque reduction neutralization test 50 (PRNT50) in the PFU assay and the half maximal inhibitory concentration (IC50) in the cytopathic/cytotoxic method (calculated as the minus log10 dilution which reduced the viral titer by 50%). Results All IVIG preparations showed neutralization of both SARS-CoV-2 isolates, ranging from 79 to 89.5% with PRNT50 titers from 4.5 to >5 for the PFU method and ranging from 47.0%-64.7% with an IC50 ~1 for the cytopathic method. All IVIG lots produced neutralization of SARS-CoV ranging from 39.5 to 55.1 % and PRNT50 values ranging from 2.0 to 3.3. No IVIG preparation showed significant neutralizing activity against MERS-CoV. Conclusion In cell culture neutralization assays, the tested IVIG products contain antibodies with significant cross-neutralization capacity against SARS-CoV-2 and SARS-CoV. However, no neutralization capacity was demonstrated against MERS-CoV. These preparations are currently available and may be immediately useful for COVID-19 management. url: https://doi.org/10.1101/2020.06.19.160879 doi: 10.1101/2020.06.19.160879 id: cord-331701-izkz1hz4 author: Eden, John-Sebastian title: An emergent clade of SARS-CoV-2 linked to returned travellers from Iran date: 2020-03-17 words: 1271.0 sentences: 70.0 pages: flesch: 50.0 cache: ./cache/cord-331701-izkz1hz4.txt txt: ./txt/cord-331701-izkz1hz4.txt summary: Phylogenetic analyses of whole genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases. Herein, we show that the genomic analyses of SARS-CoV-2 strains from Australian returned travellers with COVID-19 disease may provide important insights into viral diversity present in regions currently lacking genomic data. However, while we cannot completely discount that the cases in Australia and New Zealand came from other sources including China, our phylogenetic analyses, as well as epidemiological (recent travel to Iran) and clinical data (date of symptom onset), provide evidence that this clade of SARS-CoV-2 is linked to the Iranian epidemic, from where genomic data is currently lacking. abstract: The SARS-CoV-2 epidemic has rapidly spread outside China with major outbreaks occurring in Italy, South Korea and Iran. Phylogenetic analyses of whole genome sequencing data identified a distinct SARS-CoV-2 clade linked to travellers returning from Iran to Australia and New Zealand. This study highlights potential viral diversity driving the epidemic in Iran, and underscores the power of rapid genome sequencing and public data sharing to improve the detection and management of emerging infectious diseases. url: https://doi.org/10.1101/2020.03.15.992818 doi: 10.1101/2020.03.15.992818 id: cord-334394-qgyzk7th author: Edgar, Robert C. title: Petabase-scale sequence alignment catalyses viral discovery date: 2020-08-10 words: 8134.0 sentences: 423.0 pages: flesch: 51.0 cache: ./cache/cord-334394-qgyzk7th.txt txt: ./txt/cord-334394-qgyzk7th.txt summary: To address the ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 and expand the known sequence diversity of viruses, we aligned pangenomes for coronaviruses (CoV) and other viral families to 5.6 petabases of public sequencing data from 3.8 million biologically diverse samples. To expand the known repertoire of viruses and catalyse global virus discovery, in particular for Coronaviridae (CoV) family, we developed the Serratus cloud computing architecture for ultra-high throughput sequence alignment. We aligned 3,837,755 public RNA-seq, meta-genome, meta-virome and meta-transcriptome datasets (termed a sequencing run [5] ) against a collection of viral family pangenomes comprising all GenBank CoV records clustered at 99% identity plus all non-retroviral RefSeq records for vertebrate viruses (see Methods and Extended Table 1 ). We performed de novo assembly on 52,772 runs potentially containing CoV sequencing reads by combining 37,131 SRA accessions identified by the Serratus search with 18,584 identified by an ongoing cataloguing initiative of the SRA called STAT [5] . abstract: Public sequence data represents a major opportunity for viral discovery, but its exploration has been inhibited by a lack of efficient methods for searching this corpus, which is currently at the petabase scale and growing exponentially. To address the ongoing pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 and expand the known sequence diversity of viruses, we aligned pangenomes for coronaviruses (CoV) and other viral families to 5.6 petabases of public sequencing data from 3.8 million biologically diverse samples. To implement this strategy, we developed a cloud computing architecture, Serratus, tailored for ultra-high throughput sequence alignment at the petabase scale. From this search, we identified and assembled thousands of CoV and CoV-like genomes and genome fragments ranging from known strains to putatively novel genera. We generalise this strategy to other viral families, identifying several novel deltaviruses and huge bacteriophages. To catalyse a new era of viral discovery we made millions of viral alignments and family identifications freely available to the research community. Expanding the known diversity and zoonotic reservoirs of CoV and other emerging pathogens can accelerate vaccine and therapeutic developments for the current pandemic, and help us anticipate and mitigate future ones. url: https://doi.org/10.1101/2020.08.07.241729 doi: 10.1101/2020.08.07.241729 id: cord-102377-n57hoty4 author: Egli, Adrian title: High-resolution influenza mapping of a city reveals socioeconomic determinants of transmission within and between urban quarters date: 2020-04-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: With two-thirds of the global population projected to be living in urban areas by 2050, understanding the transmission patterns of viral pathogens within cities is crucial for effective prevention strategies. Here, in unprecedented spatial resolution, we analysed the socioeconomic determinants of influenza transmission in a European city. We combined geographical and epidemiological data with whole genome sequencing of influenza viruses at the scale of urban quarters and statistical blocks, the smallest geographic subdivisions within a city. We observed annually re-occurring geographic clusters of influenza incidences, mainly associated with net income, and independent of population density and living space. Vaccination against influenza was also mainly associated with household income and was linked to the likelihood of influenza-like illness within an urban quarter. Transmissions patterns within and between quarters were complex. High-resolution city-level epidemiological studies combined with social science surveys such as this will be essential for understanding seasonal and pandemic transmission chains and delivering tailored public health information and vaccination programs at the municipal level. url: https://doi.org/10.1101/2020.04.03.023135 doi: 10.1101/2020.04.03.023135 id: cord-102463-d440jsek author: Eguchi, Raphael R. title: IG-VAE: Generative Modeling of Immunoglobulin Proteins by Direct 3D Coordinate Generation date: 2020-08-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: While deep learning models have seen increasing applications in protein science, few have been implemented for protein backbone generation—an important task in structure-based problems such as active site and interface design. We present a new approach to building class-specific backbones, using a variational auto-encoder to directly generate the 3D coordinates of immunoglobulins. Our model is torsion- and distance-aware, learns a high-resolution embedding of the dataset, and generates novel, high-quality structures compatible with existing design tools. We show that the Ig-VAE can be used to create a computational model of a SARS-CoV2-RBD binder via latent space sampling. We further demonstrate that the model’s generative prior is a powerful tool for guiding computational protein design, motivating a new paradigm under which backbone design is solved as constrained optimization problem in the latent space of a generative model. url: https://doi.org/10.1101/2020.08.07.242347 doi: 10.1101/2020.08.07.242347 id: cord-304544-tqtdjh2m author: Enes, Ak title: Transcriptional response of signalling pathways to SARS-CoV-2 infection in normal human bronchial epithelial cells date: 2020-06-20 words: 3745.0 sentences: 189.0 pages: flesch: 49.0 cache: ./cache/cord-304544-tqtdjh2m.txt txt: ./txt/cord-304544-tqtdjh2m.txt summary: Comparison of transcriptome of NHBE cells 24 hours after mock-infection and SARS-CoV-2 infection demonstrated that most genes that respond to infection were upregulated (320 genes) rather than being downregulated (115 genes).While upregulated genes were enriched in signalling pathways related to virus response, downregulated genes are related to kidney development. Although virus entry protein ACE2 has low expression in NHBE cells, pathogen response pathways are strongly activated within 24 hours of infection. Upregulated MMPs and chemokines demonstrate the response generated by NHBE cells to trigger the immune system, these two subgroups of genes are further discussed below comparatively in SARS-CoV-2 and H1N1 infection. Interestingly, none of the IL-17 ligands were expressed in detectable amounts in NHBE cells, and none of the ligands or receptors were upregulated in response to virus infection, therefore the positive feedback loop is likely to be initiated by activation of NFκB via other signalling pathways. abstract: SARS-CoV-2 virus, the pathogen that causes Covid-19 disease, emerged in Wuhan region in China in 2019, infected more than 4M people and is responsible for death of at least 300K patients globally as of May 2020. Identification of the cellular response mechanisms to viral infection by SARS-CoV-2 may shed light on progress of the disease, indicate potential drug targets, and make design of new test methods possible. In this study, we analysed transcriptomic response of normal human bronchial epithelial cells (NHBE) to SARS-CoV-2 infection and compared the response to H1N1 infection. Comparison of transcriptome of NHBE cells 24 hours after mock-infection and SARS-CoV-2 infection demonstrated that most genes that respond to infection were upregulated (320 genes) rather than being downregulated (115 genes).While upregulated genes were enriched in signalling pathways related to virus response, downregulated genes are related to kidney development. We mapped the upregulated genes on KEGG pathways to identify the mechanisms that mediate the response. We identified canonical NFκB, TNF and IL-17 pathways to be significantly upregulated and to converge to NFκB pathway via positive feedback loops. Although virus entry protein ACE2 has low expression in NHBE cells, pathogen response pathways are strongly activated within 24 hours of infection. Our results also indicate that immune response system is activated at the early stage of the infection and orchestrated by a crosstalk of signalling pathways. Finally, we compared transcriptomic SARS-CoV-2 response to H1N1 response in NHBE cells to elucidate the virus specificity of the response and virus specific extracellular proteins expressed by NHBE cells. url: https://doi.org/10.1101/2020.06.20.163006 doi: 10.1101/2020.06.20.163006 id: cord-281699-pxof67pl author: Eskier, Doğa title: Mutations of SARS-CoV-2 nsp14 exhibit strong association with increased genome-wide mutation load date: 2020-08-13 words: 3089.0 sentences: 169.0 pages: flesch: 55.0 cache: ./cache/cord-281699-pxof67pl.txt txt: ./txt/cord-281699-pxof67pl.txt summary: In our previous study, we examined the top 10 most frequent mutations in the SARS-CoV-2 nsp12, and identified that four of them are associated with an increase in mutation density in two genes, the membrane glycoprotein (M) and the envelope glycoprotein (E) (the combination of which is hereafter referred to as MoE, as we previously described), which are not under selective pressure, and mutations in these genes are potential markers of reduced replication fidelity (Eskier et al., 2020) . To identify the trends in SARS-CoV-2 mutation load over time, we calculated the average mutation density per day for all isolates for whole genome, S gene, and MoE regions, capping outliers at the 95th and 5th percentile values to minimize the potential effects of sequencing errors ( Fig. 1) . abstract: SARS-CoV-2 is a betacoronavirus responsible for human cases of COVID-19, a pandemic with global impact that first emerged in late 2019. Since then, the viral genome has shown considerable variance as the disease spread across the world, in part due to the zoonotic origins of the virus and the human host adaptation process. As a virus with an RNA genome that codes for its own genomic replication proteins, mutations in these proteins can significantly impact the variance rate of the genome, affecting both the survival and infection rate of the virus, and attempts at combating the disease. In this study, we analyzed the mutation densities of viral isolates carrying frequently observed mutations for four proteins in the RNA synthesis complex over time in comparison to wildtype isolates. Our observations suggest mutations in nsp14, an error-correcting exonuclease protein, have the strongest association with increased mutation load in both regions without selective pressure and across the genome, compared to nsp7, 8, and 12, which form the core polymerase complex. We propose nsp14 as a priority research target for understanding genomic variance rate in SARS-CoV-2 isolates, and nsp14 mutations as potential predictors for high mutability strains. url: https://doi.org/10.1101/2020.08.12.248732 doi: 10.1101/2020.08.12.248732 id: cord-285159-gytebbua author: Eydoux, Cecilia title: A Fluorescence-based High Throughput-Screening assay for the SARS-CoV RNA synthesis complex date: 2020-07-07 words: 3603.0 sentences: 215.0 pages: flesch: 59.0 cache: ./cache/cord-285159-gytebbua.txt txt: ./txt/cord-285159-gytebbua.txt summary: Here, we report the use of a purified and highly active SARS-CoV replication/transcription complex (RTC) to set-up a high-throughput screening of Coronavirus RNA synthesis inhibitors. Principle of SARS-CoV RNA synthesis detection by a fluorescence-based high throughput screening assay Highlights A new SARS-CoV non radioactive RNA polymerase assay is described The robotized assay is suitable to identify RdRp inhibitors based on HTS -A new SARS-CoV non radioactive RNA polymerase assay is described -The robotized assay is suitable to identify RdRp inhibitors based on HTS the RdRp core nsp12 and shown to confer full activity and processivity to nsp12 (Subissi et al., 2014) . Picogreen kinetic assay was based on polymerase activity of SARS nsp12 in complex with nsp7L8, which catalyzed the reaction using a poly (A) template and uridine triphosphate (UTP). abstract: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) emergence in 2003 introduced the first serious human coronavirus pathogen to an unprepared world. To control emerging viruses, existing successful anti(retro)viral therapies can inspire antiviral strategies, as conserved viral enzymes (eg., viral proteases and RNA-dependent RNA polymerases) represent targets of choice. Since 2003, much effort has been expended in the characterization of the SARS-CoV replication/transcription machinery. Until recently, a pure and highly active preparation of SARS-CoV recombinant RNA synthesis machinery was not available, impeding target-based high throughput screening of drug candidates against this viral family. The current Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic revealed a new pathogen whose RNA synthesis machinery is highly (>96% aa identity) homologous to SARS-CoV. This phylogenetic relatedness highlights the potential use of conserved replication enzymes to discover inhibitors against this significant pathogen, which in turn, contributes to scientific preparedness against emerging viruses. Here, we report the use of a purified and highly active SARS-CoV replication/transcription complex (RTC) to set-up a high-throughput screening of Coronavirus RNA synthesis inhibitors. The screening of a small (1,520 compounds) chemical library of FDA-approved drugs demonstrates the robustness of our assay and will allow to speed-up drug repositioning or novel drug discovery against the SARS-CoV-2. Principle of SARS-CoV RNA synthesis detection by a fluorescence-based high throughput screening assay Highlights - A new SARS-CoV non radioactive RNA polymerase assay is described - The robotized assay is suitable to identify RdRp inhibitors based on HTS url: https://doi.org/10.1101/2020.07.07.192005 doi: 10.1101/2020.07.07.192005 id: cord-281684-m3m4mhye author: Fagre, Anna C. title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters date: 2020-09-28 words: 3707.0 sentences: 212.0 pages: flesch: 47.0 cache: ./cache/cord-281684-m3m4mhye.txt txt: ./txt/cord-281684-m3m4mhye.txt summary: title: A potent SARS-CoV-2 neutralizing human monoclonal antibody that reduces viral burden and disease severity in Syrian hamsters We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. However, to date, there has been only a gross histological analysis of the lung pathological changes following infection and the impact of SARS-CoV-2 neutralizing antibody clones on lung immune infiltrates has yet to be fully assessed. Those antibody clones that blocked the interaction of the RBD with ACE2 and bound to native spike protein were then tested for neutralization of SARS-CoV-2 in a cytopathic effect (CPE) assay with Vero E6 cells. Potent neutralization of severe acute respiratory syndrome (SARS) coronavirus by a human mAb to S1 protein that blocks receptor association Emergence of SARS-CoV-2 spike RBD mutants that enhance viral infectivity through increased human ACE2 receptor binding affinity abstract: The emergence of COVID-19 has led to a pandemic that has caused millions of cases of disease, variable morbidity and hundreds of thousands of deaths. Currently, only remdesivir and dexamethasone have demonstrated limited efficacy, only slightly reducing disease burden, thus novel approaches for clinical management of COVID-19 are needed. We identified a panel of human monoclonal antibody clones from a yeast display library with specificity to the SARS-CoV-2 spike protein receptor binding domain that neutralized the virus in vitro. Administration of the lead antibody clone to Syrian hamsters challenged with SARS-CoV-2 significantly reduced viral load and histopathology score in the lungs. Moreover, the antibody interrupted monocyte infiltration into the lungs, which may have contributed to the reduction of disease severity by limiting immunopathological exacerbation. The use of this antibody could provide an important therapy for treatment of COVID-19 patients. url: https://doi.org/10.1101/2020.09.25.313601 doi: 10.1101/2020.09.25.313601 id: cord-279576-wt4crton author: Fajardo, Álvaro title: Evaluation Of SYBR Green Real Time PCR For Detecting SARS-CoV-2 From Clinical Samples date: 2020-05-13 words: 4842.0 sentences: 263.0 pages: flesch: 54.0 cache: ./cache/cord-279576-wt4crton.txt txt: ./txt/cord-279576-wt4crton.txt summary: Several methods based on real time reverse transcription polymerase chain reaction (RT-qPCR) for the detection of SARS-CoV-2 genomic RNA have been developed. The aim of the study was to set up an alternative molecular protocol to detect SARS-CoV-2 from clinical samples, without the need of TaqMan probes or post-PCR steps (i.e. gel electrophoresis), which can be implemented in case of difficulties to get specific reagents or kits because of the current pandemic situation. In order to select an appropriate amount of control vector to use in the comparison between the two real time qPCR methods, we prepared plasmids dilutions (107, 106, 105 and 104 copies/μL) and assayed them following both protocols: the probe-based One Step RT-qPCR developed by the University of Hong Kong Poon et al. The amplification data for the SYBR Green-based qPCR protocol showed that the ORF1b-nsp14 region was correctly amplified for all SARS-CoV-2 positive samples (1 to 7) (Fig. 3) . abstract: The pandemic caused by SARS-CoV-2 has triggered an extraordinary collapse of healthcare systems and hundred thousand of deaths worldwide. Following the declaration of the outbreak as a Public Health Emergency of International Concern by the World Health Organization (WHO) on January 30th, 2020, it has become imperative to develop diagnostic tools to reliably detect the virus in infected patients. Several methods based on real time reverse transcription polymerase chain reaction (RT-qPCR) for the detection of SARS-CoV-2 genomic RNA have been developed. In addition, these methods have been recommended by the WHO for laboratory diagnosis. Since all these protocols are based on the use of fluorogenic probes and one-step reagents (cDNA synthesis followed by PCR amplification in the same tube), these techniques can be difficult to perform given the limited supply of reagents in low and middle income countries. In the interest of economy, time and availability of chemicals and consumables, the SYBR Green-based detection was implemented to establish a convenient assay. Therefore, we adapted one of WHO recommended Taqman-based one-step real time PCR protocols (from the University of Hong Kong) to SYBR Green. Our results suggest that SYBR-Green detection represents a reliable cost-effective alternative to increase the testing capacity. url: https://doi.org/10.1101/2020.05.13.093609 doi: 10.1101/2020.05.13.093609 id: cord-353129-ivbf4kuq author: Faryami, Ahmad title: Open source 3D printed Ventilation Device date: 2020-05-22 words: 2331.0 sentences: 118.0 pages: flesch: 50.0 cache: ./cache/cord-353129-ivbf4kuq.txt txt: ./txt/cord-353129-ivbf4kuq.txt summary: The following is intended to review the development and testing of a 3D printed and open-source mechanical ventilation device that is capable of adjusting breathing rate, volume, and pressure simultaneously and was designed according to the latest clinical observations of the current pandemic. This open-source positive pressure ventilation device (OSPPVD) is a response to the shortages in the hospitals'' ventilation capacity, which has been reported to be essential to many COVID-19 patients throughout the world. According to the initial reports published by healthcare providers, the loss of compliance due to the onset of fibrosis in the lungs is observed in patients diagnosed with severe cases of COVID-19 infection 9 . An advantage of OSPPVD presented here is its capability to perform hyperventilation with high flow rates under relatively wide pressure range from 5 2 that would allow the delivery of oxygen without the over-expansion of the lungs while being able to supply pressurized air as high as 40 or 50 2 even though the current setup is designed to only reach 30 2 . abstract: COVID-19 is an acute respiratory tract infection caused by a coronavirus known as SARS-CoV-2. The common signs of infection include respiratory symptoms such as shortness of breath, breathing difficulties, dry cough, fever, and in some patients, severe acute respiratory syndrome, kidney failure, and death. 312,009 deaths from COVID-19 has been reported as of today. While respiratory symptoms are commonly caused by the infection, the use of mechanical ventilation is required for some patients. The following is intended to review the development and testing of a 3D printed and open-source mechanical ventilation device that is capable of adjusting breathing rate, volume, and pressure simultaneously and was designed according to the latest clinical observations of the current pandemic. The intuitive design of this device along with the use of primarily 3D printed or readily available components allow the rapid manufacturing and transportation of this ventilation device to the impacted regions. url: https://doi.org/10.1101/2020.05.21.108043 doi: 10.1101/2020.05.21.108043 id: cord-329240-atisrhas author: Fedorenko, Aliza title: Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces date: 2020-06-16 words: 4493.0 sentences: 233.0 pages: flesch: 50.0 cache: ./cache/cord-329240-atisrhas.txt txt: ./txt/cord-329240-atisrhas.txt summary: Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic. To study virus survival in microdroplets deposited on a smooth inanimate surface, we sprayed Phi6, MS2, and PhiX174 viruses suspended in three media -human saliva, water, and SM bufferon glass-bottom 12-well plates (Fig. 1, Methods) . The observation that at a given RH, the microscopic hydration conditions of deposited droplets of various media can differ so widely (see along the rows of Fig. 3 ) suggests that RH does not directly affect virus stability and infectivity in drying microdroplets deposited on surfaces, but rather RH indirectly affects survival through its effect on physicochemical conditions at the scale that matters for viruses (~ µm). abstract: The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH ≥ 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic. url: https://doi.org/10.1101/2020.06.15.152983 doi: 10.1101/2020.06.15.152983 id: cord-307536-qeo5dfxg author: Feng, Ye title: Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) date: 2020-06-30 words: 998.0 sentences: 69.0 pages: flesch: 58.0 cache: ./cache/cord-307536-qeo5dfxg.txt txt: ./txt/cord-307536-qeo5dfxg.txt summary: title: Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2) When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19. Based on both the epitope counts and HLA score, we 250 eventually selected 13 T-cell epitopes-only vaccine peptides. abstract: A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides. Importance So far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19. url: https://doi.org/10.1101/2020.03.03.962332 doi: 10.1101/2020.03.03.962332 id: cord-102570-lpwwlrqm author: Fenn, Gareth D. title: Crystallization and structure of ebselen bound to cysteine 141 of human inositol monophosphatase (IMPase) date: 2020-08-18 words: 3428.0 sentences: 205.0 pages: flesch: 63.0 cache: ./cache/cord-102570-lpwwlrqm.txt txt: ./txt/cord-102570-lpwwlrqm.txt summary: In the human-IMPase-complex ebselen, in a ring opened conformation, is covalently attached to Cys141, a residue located away from the active site. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins. Synopsis Here we present a 1.47Å crystal structure of human inositol monophosphatase (IMPase) bound to the inhibitor ebselen (PDB entry 6ZK0). In this paper, we present a 1.47Å structure of ebselen covalently bound to cysteine residue 141 of human IMPase (PDB entry 6ZK0). Each monomer of IMPase in this structure has a single ebselen molecule bound to Cys141 (PDB entry 6ZK0). The IMPase crystal structure that is presented (PDB entry 6ZK0) has ebselen covalently attached to Cys141, however it is not clear to what extent this binding brings about ebselen''s inhibitory effects on IMPase. abstract: Inositol monophosphatase (IMPase) is inhibited by lithium, the most efficacious treatment for bipolar disorder. Several therapies have been approved, or are going through clinical trials, aimed at the replacement of lithium in the treatment of bipolar disorder. One candidate small molecule is ebselen, a selenium-containing antioxidant, which has been demonstrated to produce lithium-like effects, both in a murine model and in clinical trials. Here we present the crystallization and first structure of human IMPase covalently complexed with ebselen, a 1.47Å crystal structure (PDB entry 6ZK0). In the human-IMPase-complex ebselen, in a ring opened conformation, is covalently attached to Cys141, a residue located away from the active site. IMPase is a dimeric enzyme and, in the crystal structure, two adjacent dimers share four ebselen molecules, creating a tetramer with ∼222 symmetry. In the crystal structure presented in this publication, the active site in the tetramer is still accessible, suggesting that ebselen may function as an allosteric inhibitor, or may block the binding of partner proteins. Synopsis Here we present a 1.47Å crystal structure of human inositol monophosphatase (IMPase) bound to the inhibitor ebselen (PDB entry 6ZK0). In the structure, ebselen forms a seleno-sulfide bond with cysteine 141 and ebselen-mediated contacts between two dimers give a ∼222 tetramer. url: https://doi.org/10.1101/2020.07.08.193284 doi: 10.1101/2020.07.08.193284 id: cord-102964-zh737cjk author: Ferraro, Francesco title: Modulation of endothelial organelle size as an antithrombotic strategy date: 2020-05-17 words: 5532.0 sentences: 357.0 pages: flesch: 43.0 cache: ./cache/cord-102964-zh737cjk.txt txt: ./txt/cord-102964-zh737cjk.txt summary: Out of 1280 human licensed drugs we found 58 compounds fitting our criteria, with a variety of mechanisms of action consistent suggesting a number of pathways that influence biogenesis of WPBs. A quantitative high-throughput microscopy-based workflow, dubbed highthroughput morphometry (HTM), allows rapid quantification of the size of tens to hundreds of thousands of WPBs within thousands of endothelial cells (Ferraro et al., 2014) . We have previously shown that treatment of endothelial cells with two statins, simvastatin and fluvastatin, induces WPB size shortening, resulting in reduced adhesive properties of the VWF released by activated endothelial cells (HUVEC), measured by the reduced size of platelet-decorated VWF strings and by the recruitment of VWF from a flowing plasma pool (Ferraro et al., 2016) . Further to the potential toxicity associated with administration of drugs at high concentrations, we note that in vitro combination of WPB-size reducing treatments, acting through different mechanisms, can display synergy in the abatement of plasma VWF recruitment to the endothelial surface (Supplemental Figure 1) . abstract: It is long-established that Von Willebrand Factor (VWF) is central to haemostasis and thrombosis. Endothelial VWF is stored in cell-specific secretory granules, Weibel-Palade bodies (WPBs), uniquely rod-like exocytic organelles generated in a wide range of lengths (0.5 to 5.0 µm). It has been shown that WPB size responds to physiological cues and pharmacological treatment and that, under flow, VWF secretion from shortened WPBs produces a dramatic reduction of platelet and plasma VWF adhesion to an endothelial surface. WPB-shortening therefore represents a novel target for antithrombotic therapy acting via modulation of VWF adhesive activity. To this aim, we screened a library of licenced drugs and identified several that prompt WPB size reduction. These compounds therefore constitute a novel set of potentially antithrombotic compounds. Summary The size of the endothelial secretory granules that store Von Willebrand Factor correlates with its activity, central to haemostasis and thrombosis. Here, human-licenced drugs that reduce the size of these secretory granules are identified, providing a set of novel potential anti-thrombotic compounds. url: https://doi.org/10.1101/2020.05.16.099580 doi: 10.1101/2020.05.16.099580 id: cord-103606-5gbk6t6y author: Fettrow, Tyler title: Walking cadence affects the recruitment of the medial-lateral balance mechanisms date: 2019-06-03 words: 6106.0 sentences: 278.0 pages: flesch: 50.0 cache: ./cache/cord-103606-5gbk6t6y.txt txt: ./txt/cord-103606-5gbk6t6y.txt summary: We limited our analysis to the time interval from the heel-strike triggering the stimulus to the end of the second double stance post-stimulus, which encompasses the three previously identified balance mechanisms of lateral ankle roll, foot placement shift and push-off modulation. We had expected the foot placement shift to be smaller in the Low condition, due to an increased and prolonged lateral ankle mechanism response, based on modeling results (Reimann et al., 2017) . The results indicate that all three previously identified balance mechanisms are used to respond to the perceived fall, but the majority of the balance response is shifted to the lateral ankle mechanism when walking with a low cadence. We also know that people with Parkinson''s disease take shorter faster steps (Knutsson, 1972) , and although their overall gait speed is diminished, an increase in cadence may shift the majority of the balance response to the foot placement compared to age matched controls. abstract: We have previously identified three balance mechanisms that young healthy adults use to maintain balance while walking. The three mechanisms are: 1) The lateral ankle mechanism, an active modulation of ankle inversion/eversion in stance; 2) The foot placement mechanism, an active shift of the swing foot placement; and 3) The push-off mechanism, an active modulation of the ankle plantarflexion angle during double stance. Here we seek to determine whether there are changes in neural control of balance when walking at different cadences and speeds. Twenty-one healthy young adults walked on a self-paced treadmill while immersed in a 3D virtual reality cave, and periodically received balance perturbations (bipolar galvanic vestibular stimulation) eliciting a perceived fall to the side. Subjects were instructed to match two cadences specified by a metronome, 110bpm (High) and 80bpm (Low), which led to faster and slower gait speeds, respectively. The results indicate that subjects altered the use of the balance mechanisms at different cadences. The lateral ankle mechanism was used more in the Low condition, while the foot placement mechanism was used more in the High condition. There was no difference in the use of the push-off mechanism between cadence conditions. These results suggest that neural control of balance is altered when gait characteristics such as cadence change, suggesting a flexible balance response that is sensitive to the constraints of the gait cycle. We speculate that the use of the balance mechanisms may be a factor resulting in well-known characteristics of gait in populations with compromised balance control, such as slower gait speed in older adults or higher cadence in people with Parkinson’s disease. url: https://doi.org/10.1101/658070 doi: 10.1101/658070 id: cord-282878-8qgsq2km author: Fignani, Daniela title: SARS-CoV-2 receptor Angiotensin I-Converting Enzyme type 2 (ACE2) is expressed in human pancreatic β-cells and in the human pancreas microvasculature date: 2020-10-23 words: 7565.0 sentences: 359.0 pages: flesch: 43.0 cache: ./cache/cord-282878-8qgsq2km.txt txt: ./txt/cord-282878-8qgsq2km.txt summary: Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increases ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets. To address this question, we screened the ACE2 expression pattern in human pancreata obtained from adult non-diabetic multiorgan donors and in the insulin-producing human β-cell line EndoC-βH1, using different methodologies, multiple reagents, and publicly available or in-house generated RNA sequencing datasets. Here, we adopted multiple technologies and reagents to thoroughly analyse presence of ACE2, both at mRNA and protein level, in order to evaluate its expression and localization in pancreatic tissue samples obtained from adult non-diabetic multiorgan donors from the INNODIA EUnPOD biobank collection, in enzymatic-and LCM-isolated primary adult human pancreatic islets and in human β-cell line EndoC-βH1. Importantly, a recent report showed that human pancreatic islets can be infected in vitro by SARS-CoV-2 (23), supporting our observations of a specific tropism of the virus due to ACE2 expression. abstract: Increasing evidence demonstrated that the expression of Angiotensin I-Converting Enzyme type 2 (ACE2), is a necessary step for SARS-CoV-2 infection permissiveness. In the light of the recent data highlighting an association between COVID-19 and diabetes, a detailed analysis aimed at evaluating ACE2 expression pattern distribution in human pancreas is still lacking. Here, we took advantage of INNODIA network EUnPOD biobank collection to thoroughly analyse ACE2, both at mRNA and protein level, in multiple human pancreatic tissues and using several methodologies. Using multiple reagents and antibodies, we showed that ACE2 is expressed in human pancreatic islets, where it is preferentially expressed in subsets of insulin producing β-cells. ACE2 is also is highly expressed in pancreas microvasculature pericytes and moderately expressed in rare scattered ductal cells. By using different ACE2 antibodies we showed that a recently described short-ACE2 isoform is also prevalently expressed in human β-cells. Finally, using RT-qPCR, RNA-seq and High-Content imaging screening analysis, we demonstrated that pro-inflammatory cytokines, but not palmitate, increases ACE2 expression in the β-cell line EndoC-βH1 and in primary human pancreatic islets. Taken together, our data indicate a potential link between SARS-CoV-2 and diabetes through putative infection of pancreatic microvasculature and/or ductal cells and/or through direct β-cell virus tropism. url: https://doi.org/10.1101/2020.07.23.208041 doi: 10.1101/2020.07.23.208041 id: cord-312702-fruzsn26 author: Finch, Courtney L. title: Characteristic and quantifiable COVID-19-like abnormalities in CT- and PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) date: 2020-05-14 words: 2785.0 sentences: 167.0 pages: flesch: 46.0 cache: ./cache/cord-312702-fruzsn26.txt txt: ./txt/cord-312702-fruzsn26.txt summary: title: Characteristic and quantifiable COVID-19-like abnormalities in CTand PET/CT-imaged lungs of SARS-CoV-2-infected crab-eating macaques (Macaca fascicularis) Based on the rather limited X-97 ray findings in the lungs of reported NHP models of SARS-CoV-2 infection with either 98 mild or no clinical signs (11, 25, 27-29), we turned to high-resolution chest CT and 99 Increases in PCLH or PCLH/LV 169 were not seen in the mock-exposed macaques over the entire study (Figure 8a A key advantage of quantifiable CT chest imaging readout over serial euthanasia 212 studies, in addition to potentially reduced experimental animal numbers, is the ability not 213 only to evaluate between-group differences, but also to compare severity and duration of 214 disease at higher resolution in single animals and even in isolated parenchymal areas 215 sequentially. follow-up confirmation of these pilot results in this model of mild-moderate COVID-19 233 is needed to further establish quantifiable lung CT as a reliable disease readout and to 234 forge imaging-pathologic correlates in macaques euthanized at peak radiographic 235 abnormality. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing an exponentially increasing number of coronavirus disease 19 (COVID-19) cases globally. Prioritization of medical countermeasures for evaluation in randomized clinical trials is critically hindered by the lack of COVID-19 animal models that enable accurate, quantifiable, and reproducible measurement of COVID-19 pulmonary disease free from observer bias. We first used serial computed tomography (CT) to demonstrate that bilateral intrabronchial instillation of SARS-CoV-2 into crab-eating macaques (Macaca fascicularis) results in mild-to-moderate lung abnormalities qualitatively characteristic of subclinical or mild-to-moderate COVID-19 (e.g., ground-glass opacities with or without reticulation, paving, or alveolar consolidation, peri-bronchial thickening, linear opacities) at typical locations (peripheral>central, posterior and dependent, bilateral, multi-lobar). We then used positron emission tomography (PET) analysis to demonstrate increased FDG uptake in the CT-defined lung abnormalities and regional lymph nodes. PET/CT imaging findings appeared in all macaques as early as 2 days post-exposure, variably progressed, and subsequently resolved by 6–12 days post-exposure. Finally, we applied operator-independent, semi-automatic quantification of the volume and radiodensity of CT abnormalities as a possible primary endpoint for immediate and objective efficacy testing of candidate medical countermeasures. url: https://www.ncbi.nlm.nih.gov/pubmed/32511338/ doi: 10.1101/2020.05.14.096727 id: cord-255888-znfgh78m author: Fisher, Dale title: Seeding of outbreaks of COVID-19 by contaminated fresh and frozen food date: 2020-08-18 words: 1816.0 sentences: 110.0 pages: flesch: 58.0 cache: ./cache/cord-255888-znfgh78m.txt txt: ./txt/cord-255888-znfgh78m.txt summary: SARS-CoV-2 was detected on workers and environmental samples, including a cutting board used to slice imported salmon. We have assessed the survival of SARS-CoV-2 on refrigerated and frozen meat and salmon over 3 weeks to assess the potential of outbreaks being seeded by imported contaminated food. The clusters of infection of COVID-19 among workers in slaughterhouses and meat processing facilities in many countries can be attributed to factors that promote transmission of virus directly between workers, such as crowding, poor ventilation, and shouting in close proximity due to high ambient noise levels. With a significant burden of virus present in infected workers and the environment then contamination of meat with SARS-CoV-2 is possible during butchering and processing. Our laboratory work has shown that SARS-CoV-2 can survive the time and temperatures associated with transportation and storage conditions associated with international food trade. We believe it is possible that contaminated imported food can transfer virus to workers as well as the environment. abstract: An explanation is required for the re-emergence of COVID-19 outbreaks in regions with apparent local eradication. Recent outbreaks have emerged in Vietnam, New Zealand and parts of China where there had been no cases for some months. Importation of contaminated food and food packaging is a feasible source for such outbreaks and a source of clusters within existing outbreaks. Such events can be prevented if the risk is better appreciated. url: https://doi.org/10.1101/2020.08.17.255166 doi: 10.1101/2020.08.17.255166 id: cord-103135-nly9vojr author: Fletcher, Nicola F. title: A novel antiviral formulation inhibits a range of enveloped viruses date: 2020-03-30 words: 6468.0 sentences: 329.0 pages: flesch: 47.0 cache: ./cache/cord-103135-nly9vojr.txt txt: ./txt/cord-103135-nly9vojr.txt summary: ViroSAL had no effect on the infectivity of a non-enveloped virus, norovirus, which is in agreement with previous studies demonstrating that free fatty acids are ineffective against nonenveloped viruses (Thormar et al., 1987 , Kohn et al., 1980 . In this study, ViroSAL at the indicated concentrations was mixed with an equal volume of viral inoculum (MeV:original TCID50 = 4.48 7 /mL, HSV-1: 100 PFU/mL, EBV: MOI=10, Zika: MOI=10, Orf: 4 PFU/mL) or pseudoviruses bearing VSV, Ebola, Lassa or SARS-CoV-1 envelope glycoproteins, and incubated at room temperature for 2 minutes. Virus/ViroSAL or control treated virus was inoculated onto appropriate target cells and incubated for 48h at 37°C, then fixed and infection enumerated, or, for pseudovirus assays, lysed and luciferase activity quantified as previously described (Fletcher et al., 2015) . Milk-based free fatty acids, as well as fatty acid emulsions, have been shown to inhibit infection of Vero cells with VSV and HSV-1, with no antiviral effect on poliovirus, a non-enveloped virus (Thormar et al., 1987) . abstract: Some free fatty acids derived from milk and vegetable oils are known to have potent antiviral and antibacterial properties. However, therapeutic applications of short to medium chain fatty acids are limited by physical characteristics such as immiscibility in aqueous solutions. We evaluated a novel proprietary formulation based on an emulsion of short chain caprylic acid, ViroSAL, for its ability to inhibit a range of viral infections in vitro and in vivo. In vitro, ViroSAL inhibited the enveloped viruses Epstein-Barr, measles, herpes simplex, Zika and orf parapoxvirus, together with Ebola, Lassa, vesicular stomatitis and SARS-CoV-1 pseudoviruses, in a concentration- and time-dependent manner. Evaluation of the components of ViroSAL revealed that caprylic acid was the main antiviral component; however, the ViroSAL formulation significantly inhibited viral entry compared with caprylic acid alone. In vivo, ViroSAL significantly inhibited Zika and Semliki Forest Virus replication in mice following the inoculation of these viruses into mosquito bite sites. In agreement with studies investigating other free fatty acids, ViroSAL had no effect on norovirus, a non-enveloped virus, indicating that its mechanism of action may be via surfactant disruption of the viral envelope. We have identified a novel antiviral formulation that is of great interest for prevention and/or treatment of a broad range of enveloped viruses. url: https://doi.org/10.1101/2020.03.29.009464 doi: 10.1101/2020.03.29.009464 id: cord-326866-nbd4arhx author: Fox, Charles W. title: The representation of women as authors of submissions to ecology journals during the COVID-19 pandemic date: 2020-05-29 words: 1947.0 sentences: 86.0 pages: flesch: 55.0 cache: ./cache/cord-326866-nbd4arhx.txt txt: ./txt/cord-326866-nbd4arhx.txt summary: At these six ecology journals there is no evidence of a decline in the proportion of submissions that are authored by women (as either first or submitting author) since the start of the COVID-19 disruptions; the proportion of papers authored by women in the post-COVID period of 2020 has increased relative to the same period in 2019, and is higher than in the period pre-COVID in 2020. At these six ecology journals there is no evidence of a decline in the proportion of submissions that are authored by women (as either first or submitting author) since the start of the COVID-19 disruptions; the proportion of papers authored by women in the post-COVID period of 2020 has increased relative to the same period in 2019, and is higher than in the period pre-COVID in 2020. abstract: Observations made from papers submitted to preprint servers, and the speculation of editors on social media platforms, suggest that women are submitting fewer papers to scholarly journals than are men during the COVID-19 pandemic. Here I examine whether submissions by men and women to six ecology journals (all published by the British Ecological Society) have changed since the start of COVID disruptions. At these six ecology journals there is no evidence of a decline in the proportion of submissions that are authored by women (as either first or submitting author) since the start of the COVID-19 disruptions; the proportion of papers authored by women in the post-COVID period of 2020 has increased relative to the same period in 2019, and is higher than in the period pre-COVID in 2020. There is also no evidence of a change in the geographic pattern of submissions from across the globe. url: https://doi.org/10.1101/2020.05.29.123455 doi: 10.1101/2020.05.29.123455 id: cord-343027-ks3fn9pq author: Fraser, Nicholas title: Preprinting the COVID-19 pandemic date: 2020-09-18 words: 5707.0 sentences: 324.0 pages: flesch: 56.0 cache: ./cache/cord-343027-ks3fn9pq.txt txt: ./txt/cord-343027-ks3fn9pq.txt summary: When the data was broken down by server, it 132 was evident that whilst posting of COVID-19 preprints to bioRxiv had remained relatively steady, 133 preprints posted to medRxiv increased with time (Supplemental Fig. 2A) . Server usage differences were more pronounced 237 for COVID-19 preprints; multiple post-hoc comparisons confirmed that bioRxiv and medRxiv received 238 significantly higher usage per COVID-19 preprint than all other servers for which data was available 239 (Tukey HSD; all p values < 0.001). However, for non COVID-19 preprints, the only observed pairwise 240 differences between servers indicated greater bioRxiv usage than SSRN or Research Square (Tukey 241 HSD; all p values < 0.001). We also compared rates of PDF downloads for bioRxiv and medRxiv preprints 506 with a number of other preprint servers (Preprints.org, SSRN, and Research Square) (Supplemental Counts of multiple altmetric indicators (mentions in tweets, blogs, and news articles) were retrieved 510 via Altmetric (https://www.altmetric.com), a service that monitors and aggregates mentions to 511 scientific articles on various online platforms. abstract: The world continues to face an ongoing viral pandemic that presents a serious threat to human health. The virus underlying the COVID-19 disease, SARS-CoV-2, caused over 29 million confirmed cases and 925,000 deaths since January 2020. Although the last pandemic occurred only a decade ago, the way science operates and responds to current events has experienced a paradigm shift in the interim. The scientific community responded rapidly to the COVID-19 pandemic, releasing over 16,000 COVID-19 scientific articles within 4 months of the first confirmed case, of which 6,753 were hosted by preprint servers. Focussing on bioRxiv and medRxiv, two growing preprint servers for biomedical research, we investigated the attributes of COVID-19 preprints, their access and usage rates and characteristics of sharing across online platforms. Our results highlight the unprecedented role of preprint servers in the dissemination of COVID-19 science, and the impact of the pandemic on the scientific communication landscape. url: https://doi.org/10.1101/2020.05.22.111294 doi: 10.1101/2020.05.22.111294 id: cord-103964-k6jnv87v author: Friedl, Jana title: More than just a ticket canceller: The mitochondrial processing peptidase matures complex precursor proteins at internal cleavage sites date: 2020-07-03 words: 2329.0 sentences: 150.0 pages: flesch: 52.0 cache: ./cache/cord-103964-k6jnv87v.txt txt: ./txt/cord-103964-k6jnv87v.txt summary: title: More than just a ticket canceller: The mitochondrial processing peptidase matures complex precursor proteins at internal cleavage sites After import into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase MPP, giving rise to shorter mature proteins. Arg5,6 is synthesized as a polyprotein precursor that is imported into the mitochondrial matrix and subsequently separated into two distinct enzymes that function in arginine biogenesis. Our data suggest that, in addition to its role as "ticket canceller" for the removal of presequences, MPP exhibits a second, widely conserved activity as internal processing peptidase for complex mitochondrial precursor proteins. We conclude that Arg5,6 is imported into the mitochondrial matrix 104 via the presequence pathway and cleaved into separate polypeptides inside mitochondria. Incubation of radiolabeled Arg5,6 precursor protein with MPP resulted in the formation of smaller 124 fragments whose size perfectly matched those that were generated after import into isolated 125 mitochondria (Fig. 1E ). abstract: Most mitochondrial proteins are synthesized in the cytosol as precursors that carry N-terminal presequences. After import into mitochondria, these targeting signals are cleaved off by the mitochondrial processing peptidase MPP, giving rise to shorter mature proteins. Using the mitochondrial tandem protein Arg5,6 as a model substrate, we demonstrate that MPP has an additional role in preprotein maturation, beyond the removal of presequences. Arg5,6 is synthesized as a polyprotein precursor that is imported into the mitochondrial matrix and subsequently separated into two distinct enzymes that function in arginine biogenesis. This internal processing is performed by MPP, which cleaves the Arg5,6 precursor both at its N-terminus and at an internal site between the Arg5 and Arg6 parts. The peculiar organization and biogenesis of Arg5,6 is conserved across fungi and might preserve the mode of co-translational subunit association of the arginine biosynthesis complex of the polycistronic arginine operon in prokaryotic mitochondrial ancestors. Putative MPP cleavage sites are also present at the junctions in other mitochondrial fusion proteins from fungi, plants and animals. Our data suggest that, in addition to its role as “ticket canceller” for the removal of presequences, MPP exhibits a second, widely conserved activity as internal processing peptidase for complex mitochondrial precursor proteins. url: https://doi.org/10.1101/2020.07.02.183996 doi: 10.1101/2020.07.02.183996 id: cord-103176-hfd8ur9a author: Frost, H. Robert title: Variance-adjusted Mahalanobis (VAM): a fast and accurate method for cell-specific gene set scoring date: 2020-02-19 words: 7407.0 sentences: 305.0 pages: flesch: 46.0 cache: ./cache/cord-103176-hfd8ur9a.txt txt: ./txt/cord-103176-hfd8ur9a.txt summary: Unfortunately, statistical and biological differences between single cell and bulk expression measurements make it challenging to use gene set testing methods originally developed for bulk tissue on scRNA-seq data and progress on single cell-specific methods has been limited. To address this challenge, we have developed a new gene set testing method, variance-adjusted Mahalanobis (VAM), that seamlessly integrates with the Seurat framework and is designed to accommodate the technical noise, sparsity and large sample sizes characteristic of scRNA-seq data. While these methods have proven effective for the analysis of bulk expression data, with GSVA and ssGSEA among the most popular techniques, the application of these methods to scRNA-seq data is limited by three main factors: poor classification performance in the presence of sparsity and technical noise, lack of inference support on the single cell level, and high computational cost (esp. abstract: Single cell RNA sequencing (scRNA-seq) is a powerful tool for analyzing complex tissues with recent advances enabling the transcriptomic profiling of thousands to tens-of-thousands of individual cells. Although scRNA-seq provides unprecedented insights into the biology of heterogeneous cell populations, analyzing such data on a gene-by-gene basis is challenging due to the large number of tested hypotheses, high level of technical noise and inflated zero counts. One promising approach for addressing these challenges is gene set testing, or pathway analysis. By combining the expression data for all genes in a pathway, gene set testing can mitigate the impacts of sparsity and noise and improve interpretation, replication and statistical power. Unfortunately, statistical and biological differences between single cell and bulk expression measurements make it challenging to use gene set testing methods originally developed for bulk tissue on scRNA-seq data and progress on single cell-specific methods has been limited. To address this challenge, we have developed a new gene set testing method, variance-adjusted Mahalanobis (VAM), that seamlessly integrates with the Seurat framework and is designed to accommodate the technical noise, sparsity and large sample sizes characteristic of scRNA-seq data. The VAM method computes cell-specific pathway scores to transform a cell-by-gene matrix into a cell-by-pathway matrix that can be used for both exploratory data visualization and statistical gene set enrichment analysis. Because the distribution of these scores under the null of uncorrelated technical noise has an accurate gamma approximation, inference can be performed at both the population and single cell levels. As we demonstrate using both simulation studies and real data analyses, the VAM method provides superior classification accuracy at a lower computation cost relative to existing single sample gene set testing approaches. url: https://doi.org/10.1101/2020.02.18.954321 doi: 10.1101/2020.02.18.954321 id: cord-297787-t9neub6d author: Fu, Ziyang title: Structural basis for the inhibition of the papain-like protease of SARS-CoV-2 by small molecules date: 2020-07-18 words: 2152.0 sentences: 149.0 pages: flesch: 64.0 cache: ./cache/cord-297787-t9neub6d.txt txt: ./txt/cord-297787-t9neub6d.txt summary: The co-crystal structure of SARS-CoV-2 PLpro-C111S in complex with GRL0617 suggests that GRL0617 is a non-covalent inhibitor. The antiviral activity of GRL0617 reveal that PLpro is a promising drug target for therapeutically treating COVID-19. The in-vitro 85 IC50 of GRL0617 against SARS-COV-2 PLpro was 2.1 ± 0.2 μM, suggesting a promising lead 86 compound and therefore it was subjected to further structural and mechanistic studies ( Fig. 2A) . Taken together, our NMR and X-ray analysis indicates that GRL0617 162 is a potent PPI (protein-protein interaction) inhibitor for PLpro blocking the binding of ISG15. Our co-crystal structure of PLpro C111S in complex with the potent 175 inhibitor GRL0617 validated that SARS-COV-2 PLpro is a druggable target. Based on the structure, GRL0617 resides in the S3/S4 site of PLpro, naturally it will also 179 inhibit the processing of viral polyproteins of SARS-CoV-2 since these viral polyproteins share the 180 same substrate cleavage sequence with Ub and ISG15. The SARS-coronavirus papain-like 257 protease: structure, function and inhibition by designed antiviral compounds abstract: SARS-CoV-2 is the pathogen responsible for the COVID-19 pandemic. The SARS-CoV-2 papain-like cysteine protease has been implicated in virus maturation, dysregulation of host inflammation and antiviral immune responses. We showed that PLpro preferably cleaves the K48-ubiquitin linkage while also being capable of cleaving ISG15 modification. The multiple functions of PLpro render it a promising drug target. Therefore, we screened an FDA-approved drug library and also examined available inhibitors against PLpro. Inhibitor GRL0617 showed a promising IC50 of 2.1 μM. The co-crystal structure of SARS-CoV-2 PLpro-C111S in complex with GRL0617 suggests that GRL0617 is a non-covalent inhibitor. NMR data indicate that GRL0617 blocks the binding of ISG15 to PLpro. The antiviral activity of GRL0617 reveal that PLpro is a promising drug target for therapeutically treating COVID-19. One Sentence Summary Co-crystal structure of PLpro in complex with GRL0617 reveals the druggability of PLpro for SARS-CoV-2 treatment. url: https://doi.org/10.1101/2020.07.17.208959 doi: 10.1101/2020.07.17.208959 id: cord-311333-shvtfxog author: Fukumoto, Tatsuya title: Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification date: 2020-05-28 words: 414.0 sentences: 37.0 pages: flesch: 70.0 cache: ./cache/cord-311333-shvtfxog.txt txt: ./txt/cord-311333-shvtfxog.txt summary: title: Efficacy of a novel SARS-CoV-2 detection kit without RNA extraction and purification The virus was detected in 53/71 fresh samples by the direct method and 55/71 corresponding frozen samples by the nCoV-DK. Concordance rates were 95.2% (95% CI, 83.8-99.4), 95.5% (95% CI, 77.2-99.9), 85.7% (95% CI, 42.1-99.6) in nasopharyngeal swab, saliva, and sputum samples, respectively. These results indicate that the nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error. Nasopharyngeal swab, sputum and saliva samples were collected from 9 patients who 69 were admitted to our hospital after a diagnosis of COVID-19. Saliva as a 187 non-invasive specimen for detection of SARS-CoV-2 Comparison of SARS-CoV-2 detection in nasopharyngeal swab and saliva Detection of noroviruses in fecal specimens by direct RT-PCR 195 without RNA purification abstract: Rapid detection of SARS-CoV-2 is critical for the diagnosis of coronavirus disease 2019 (COVID-19) and preventing the spread of the virus. A novel “2019 Novel Coronavirus Detection Kit (nCoV-DK)” halves detection time by eliminating the steps of RNA extraction and purification. We evaluated concordance between the nCoV-DK and direct PCR. The virus was detected in 53/71 fresh samples by the direct method and 55/71 corresponding frozen samples by the nCoV-DK. The overall concordance rate of the virus detection between the two methods was 94.4% (95% CI, 86.2-98.4). Concordance rates were 95.2% (95% CI, 83.8-99.4), 95.5% (95% CI, 77.2-99.9), 85.7% (95% CI, 42.1-99.6) in nasopharyngeal swab, saliva, and sputum samples, respectively. These results indicate that the nCoV-DK effectively detects SARS-CoV-2 in all types of the samples including saliva, while reducing time required for detection, labor, and risk of human error. url: https://doi.org/10.1101/2020.05.27.120410 doi: 10.1101/2020.05.27.120410 id: cord-103180-5hkoeca7 author: Furstenau, Tara N. title: Sample pooling methods for efficient pathogen screening: Practical implications date: 2020-07-16 words: 3789.0 sentences: 174.0 pages: flesch: 59.0 cache: ./cache/cord-103180-5hkoeca7.txt txt: ./txt/cord-103180-5hkoeca7.txt summary: Sample pooling methods improve the efficiency of large-scale pathogen screening campaigns by reducing the number of tests and reagents required to accurately categorize positive and negative individuals. Here we use computational simulations to determine how several theoretical approaches compare in terms of (a) the number of tests, to minimize costs and save reagents, (b) the number of sequential steps, to reduce the time it takes to complete the assay, (c) the number of samples per pool, to avoid the limits of detection, (d) simplicity, to reduce the risk of human error, and (e) robustness, to poor estimates of the number of positive samples. 25 Due to practical concerns, Dorfman''s group testing approach was never applied to 26 syphilis screening because the large number of negative samples had a tendency to 27 dilute the antigen in positive samples below the level of detection [6] . abstract: Due to the large number of negative tests, individually screening large populations for rare pathogens can be wasteful and expensive. Sample pooling methods improve the efficiency of large-scale pathogen screening campaigns by reducing the number of tests and reagents required to accurately categorize positive and negative individuals. Such methods rely on group testing theory which mainly focuses on minimizing the total number of tests; however, many other practical concerns and tradeoffs must be considered when choosing an appropriate method for a given set of circumstances. Here we use computational simulations to determine how several theoretical approaches compare in terms of (a) the number of tests, to minimize costs and save reagents, (b) the number of sequential steps, to reduce the time it takes to complete the assay, (c) the number of samples per pool, to avoid the limits of detection, (d) simplicity, to reduce the risk of human error, and (e) robustness, to poor estimates of the number of positive samples. We found that established methods often perform very well in one area but very poorly in others. Therefore, we introduce and validate a new method which performs fairly well across each of the above criteria making it a good general use approach. url: https://doi.org/10.1101/2020.07.16.206060 doi: 10.1101/2020.07.16.206060 id: cord-103654-k02z72gb author: Gamboa Arana, Olga Lucia title: Dose-dependent enhancement of motion direction discrimination with transcranial magnetic stimulation of visual cortex date: 2020-06-15 words: 5839.0 sentences: 241.0 pages: flesch: 38.0 cache: ./cache/cord-103654-k02z72gb.txt txt: ./txt/cord-103654-k02z72gb.txt summary: Studies of motion perception are particularly well-suited for exploring mechanisms of TMS due to the superficial location of motion sensitive cortex and its well-characterized spatiotemporal progression of electroencephalographic (EEG) activation described by the P1/N2/P3 Visual Evoked Potential (VEP) complex. For this purpose, we used a three-visit study design consisting of an initial dose-finding session to derive individualized motion coherence thresholds and stimulation parameters based on the onset of the N2 VEP component ("N2-Onset"), followed by two dose-testing sessions during which spTMS was delivered according to the spatial, temporal, and intensity parameters derived from the first session. The overall goal was to map the behavioral and evoked EEG dose-response functions within the constructs of individualized spatiotemporal targeting with the expectation that spTMS delivered at the onset of the N2 component would disrupt motion processes in the brain and lead to monotonic effects across different stimulation intensities. abstract: Despite the widespread use of transcranial magnetic stimulation (TMS) in research and clinical care, the underlying mechanisms-of-actions that mediate modulatory effects remain poorly understood. To fill this gap, we studied dose–response functions of TMS for modulation of visual processing. Our approach combined electroencephalography (EEG) with application of single pulse TMS to visual cortex as participants performed a motion perception task. During participants’ first visit, motion coherence thresholds, 64-channel visual evoked potentials (VEPs), and TMS resting motor thresholds (RMT) were measured. In second and third visits, single pulse TMS was delivered 30 ms before the onset of motion or at the onset latency of the N2 VEP component derived from the first session. TMS was delivered at 0%, 80%, 100%, or 120% of RMT over the site of N2 peak activity, or at 120% over vertex. Behavioral results demonstrated a significant main effect of TMS timing on accuracy, with better performance when TMS was applied at N2-Onset timing versus Pre-Onset, as well as a significant interaction, indicating that 80% intensity produced higher accuracy than other conditions. TMS effects on VEPs showed reduced amplitudes in the 80% Pre-Onset condition, an increase for the 120% N2-Onset condition, and monotonic amplitude scaling with stimulation intensity. The N2 component was not affected by TMS. These findings reveal dose–response relationships between intensity and timing of TMS on visual perception and electrophysiological brain activity, generally indicating greater facilitation at stimulation intensities below RMT. url: https://doi.org/10.1101/2020.06.14.151118 doi: 10.1101/2020.06.14.151118 id: cord-103497-1ls2dvzy author: Ganier, C title: CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals date: 2020-05-29 words: 1427.0 sentences: 90.0 pages: flesch: 53.0 cache: ./cache/cord-103497-1ls2dvzy.txt txt: ./txt/cord-103497-1ls2dvzy.txt summary: title: CD147 (BSG) but not ACE2 expression is detectable in vascular endothelial cells within single cell RNA sequencing datasets derived from multiple tissues in healthy individuals To define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 as well as other genes implicated in the cellular entry of SARS-Cov-2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). The ACE2 receptor has been shown to mediate uptake of the virus responsible for COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in human cells (Hoffmann, Kleine-Weber, Schroeder, et al. In order to define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). abstract: Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with a wide range of systemic manifestations. Several observations support a role for vascular endothelial dysfunction in the pathogenesis including an increased incidence of thrombotic events and coagulopathy and the presence of vascular risk factors as an independent predictor of poor prognosis. It has recently been reported that endothelitis is associated with viral inclusion bodies suggesting a direct role for SARS-CoV-2 in the pathogenesis. The ACE2 receptor has been shown to mediate SARS-CoV-2 uptake and it has been proposed that CD147 (BSG) can function as an alternative cell surface receptor. To define the endothelial cell populations that are susceptible to infection with SARS-CoV-2, we investigated the expression of ACE2 as well as other genes implicated in the cellular entry of SARS-Cov-2 in the vascular endothelium through the analysis of single cell sequencing data derived from multiple human tissues (skin, liver, kidney, lung and intestine). We found that CD147 (BSG) but not ACE2 is detectable in vascular endothelial cells within single cell sequencing datasets derived from multiple tissues in healthy individuals. This implies that either ACE2 is not expressed in healthy tissue but is instead induced in response to SARS-Cov2 or that SARS-Cov2 enters endothelial cells via an alternative receptor such as CD147. url: https://doi.org/10.1101/2020.05.29.123513 doi: 10.1101/2020.05.29.123513 id: cord-255552-k1retwa4 author: Gassen, Nils C. title: Analysis of SARS-CoV-2-controlled autophagy reveals spermidine, MK-2206, and niclosamide as putative antiviral therapeutics date: 2020-04-15 words: 1208.0 sentences: 73.0 pages: flesch: 39.0 cache: ./cache/cord-255552-k1retwa4.txt txt: ./txt/cord-255552-k1retwa4.txt summary: Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In the case of highly pathogenic Middle East respiratory syndrome 57 (MERS)-CoV, we recently showed that autophagy is limited by a virus-induced AKT1-dependent 58 activation of the E3-ligase S-phase kinase-associated protein 2 (SKP2), which targets the key autophagy 59 initiating protein Beclin-1 (BECN1) for proteasomal degradation (10). Direct blocking of the negative BECN1 regulator SPK2 by previously 175 described inhibitors SMIP004, SMIP004-7, valinomycin, and niclosamide (10) showed SARS-CoV-2 176 growth inhibition from 50 (SMIP004, SMIP004-7) to over 99% in case of valinomycin and niclosamide 177 (Figure 4a, lower panel, Figure S3d,e) . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses an acute threat to public health and the world economy, especially because no approved specific drugs or vaccines are available. Pharmacological modulation of metabolism-dependent cellular pathways such as autophagy reduced propagation of highly pathogenic Middle East respiratory syndrome (MERS)-CoV. Here we show that SARS-CoV-2 infection limits autophagy by interfering with multiple metabolic pathways and that compound-driven interventions aimed at autophagy induction reduce SARS-CoV-2 propagation in vitro. In-depth analyses of autophagy signaling and metabolomics indicate that SARS-CoV-2 reduces glycolysis and protein translation by limiting activation of AMP-protein activated kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1). Infection also downregulates autophagy-inducing spermidine, and facilitates AKT1/SKP2-dependent degradation of autophagy-initiating Beclin-1 (BECN1). Targeting of these pathways by exogenous administration of spermidine, AKT inhibitor MK-2206, and the Beclin-1 stabilizing, antihelminthic drug niclosamide inhibited SARS-CoV-2 propagation by 85, 88, and >99%, respectively. In sum, SARS-CoV-2 infection causally diminishes autophagy. A clinically approved and well-tolerated autophagy-inducing compound shows potential for evaluation as a treatment against SARS-CoV-2. url: https://doi.org/10.1101/2020.04.15.997254 doi: 10.1101/2020.04.15.997254 id: cord-302920-jkr438p9 author: Gasser, Romain title: Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 date: 2020-10-09 words: 423.0 sentences: 31.0 pages: flesch: 48.0 cache: ./cache/cord-302920-jkr438p9.txt txt: ./txt/cord-302920-jkr438p9.txt summary: key: cord-302920-jkr438p9 title: Major role of IgM in the neutralizing activity of convalescent plasma against SARS-CoV-2 cord_uid: jkr438p9 Characterization of the humoral response to SARS-CoV-2, the etiological agent of Covid-19, is essential to help control the infection. In this regard, we and others recently reported that the neutralization activity of plasma from COVID-19 patients decreases rapidly during the first weeks after recovery. In this study, we selected plasma from a cohort of Covid-19 convalescent patients and selectively depleted immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of IgM. Decline of humoral 409 responses against SARS-CoV-2 Spike in convalescent individuals Potent neutralizing 413 antibodies from COVID-19 patients define multiple targets of vulnerability abstract: Characterization of the humoral response to SARS-CoV-2, the etiological agent of Covid-19, is essential to help control the infection. In this regard, we and others recently reported that the neutralization activity of plasma from COVID-19 patients decreases rapidly during the first weeks after recovery. However, the specific role of each immunoglobulin isotype in the overall neutralizing capacity is still not well understood. In this study, we selected plasma from a cohort of Covid-19 convalescent patients and selectively depleted immunoglobulin A, M or G before testing the remaining neutralizing capacity of the depleted plasma. We found that depletion of immunoglobulin M was associated with the most substantial loss of virus neutralization, followed by immunoglobulin G. This observation may help design efficient antibody-based COVID-19 therapies and may also explain the increased susceptibility to SARS-CoV-2 of autoimmune patients receiving therapies that impair the production of IgM. url: https://doi.org/10.1101/2020.10.09.333278 doi: 10.1101/2020.10.09.333278 id: cord-307701-fujejfwb author: Gaurav, Shubham title: Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype date: 2020-06-07 words: 2069.0 sentences: 111.0 pages: flesch: 54.0 cache: ./cache/cord-307701-fujejfwb.txt txt: ./txt/cord-307701-fujejfwb.txt summary: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the cause of the novel human Corona Virus Disease COVID-19, first reported on November 17 th , 2019 in Wuhan, China [12] . In addition to structural and NSPs, SARS-CoV-2 genome also codes for at least two other viroporin candidates (other than the E protein), namely ORF3a and ORF8 [3] . Moreover, the 29-nucleotide deleted SARS CoV-1 strain had a 23-fold less viral replication as compared to its wild type, suggesting that this mutation effectively attenuated the virus. abstract: Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development. url: https://doi.org/10.1101/2020.06.06.137604 doi: 10.1101/2020.06.06.137604 id: cord-280979-0vaarrji author: Gauttier, V. title: Tissue-resident memory CD8 T-cell responses elicited by a single injection of a multi-target COVID-19 vaccine date: 2020-08-14 words: 4302.0 sentences: 227.0 pages: flesch: 40.0 cache: ./cache/cord-280979-0vaarrji.txt txt: ./txt/cord-280979-0vaarrji.txt summary: These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1-biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution. These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution. Altogether, these data showed that optimized peptide vaccination against selected SARS-CoV-2 epitopes elicits robust and broad Th1-biased immunogenicity against several structural (S, M, N) and non-structural proteins in HLA-A2 expressing mice and that several peptides induce viral-specific memory CD8 T cells displaying all characteristics of T lymphocyte sentinels in barrier tissues. Using sequence design through reverse vaccinology selection approach based on previous CoVs knowledge on immunodominant epitopes and computational immunology optimization, we developed a combination of 12 CD8 T cell synthetic peptides originating from 11 SARS-CoV-2 structural and non-structural proteins capable to cover HLA polymorphism with high coverage globally and to induce immunogenicity to different proteins independently of HLA alleles expression. abstract: The COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which enters the body principally through the nasal and larynx mucosa and progress to the lungs through the respiratory tract. SARS-CoV-2 replicates efficiently in respiratory epithelial cells motivating the development of alternative and rapidly scalable vaccine inducing mucosal protective and long-lasting immunity. We have previously developed an immunologically optimized multi-neoepitopes-based peptide vaccine platform which has already demonstrated tolerance and efficacy in hundreds of lung cancer patients. Here, we present a multi-target CD8 T cell peptide COVID-19 vaccine design targeting several structural (S, M, N) and non-structural (NSPs) SARS-CoV-2 proteins with selected epitopes in conserved regions of the SARS-CoV-2 genome. We observed that a single subcutaneous injection of a serie of epitopes induces a robust immunogenicity in-vivo as measured by IFNγ ELIspot. Upon tetramer characterization we found that this serie of epitopes induces a strong proportion of virus-specific CD8 T cells expressing CD103, CD44, CXCR3 and CD49a, the specific phenotype of tissue-resident memory T lymphocytes (Trm). Finally, we observed broad cellular responses, as characterized by IFNγ production, upon restimulation with structural and non-structural protein-derived epitopes using blood T cells isolated from convalescent asymptomatic, moderate and severe COVID-19 patients. These data provide insights for further development of a second generation of COVID-19 vaccine focused on inducing lasting Th1-biased memory CD8 T cell sentinels protection using immunodominant epitopes naturally observed after SARS-CoV-2 infection resolution. Statement of Significance Humoral and cellular adaptive immunity are different and complementary immune defenses engaged by the body to clear viral infection. While neutralizing antibodies have the capacity to block virus binding to its entry receptor expressed on human cells, memory T lymphocytes have the capacity to eliminate infected cells and are required for viral clearance. However, viruses evolve quickly, and their antigens are prone to mutations to avoid recognition by the antibodies (phenomenon named ‘antigenic drift’). This limitation of the antibody-mediated immunity could be addressed by the T-cell mediated immunity, which is able to recognize conserved viral peptides from any viral proteins presented by virus-infected cells. Thus, by targeting several proteins and conserved regions on the genome of a virus, T-cell epitope-based vaccines are less subjected to mutations and may work effectively on different strains of the virus. We designed a multi-target T cell-based vaccine containing epitope regions optimized for CD8+ T cell stimulation that would drive long-lasting cellular immunity with high specificity, avoiding undesired effects such as antibody-dependent enhancement (ADE) and antibody-induced macrophages hyperinflammation that could be observed in subjects with severe COVID-19. Our in-vivo results showed that a single injection of selected CD8 T cell epitopes induces memory viral-specific T-cell responses with a phenotype of tissue-resident memory T cells (Trm). Trm has attracted a growing interest for developing vaccination strategies since they act as immune sentinels in barrier tissue such as the respiratory tract and the lung. Because of their localization in tissues, they are able to immediately recognize infected cells and, because of their memory phenotypes, they rapidly respond to viral infection by orchestrating local protective immune responses to eliminate pathogens. Lastly, such multiepitope-based vaccination platform uses robust and well-validated synthetic peptide production technologies that can be rapidly manufactured in a distributed manner. url: https://doi.org/10.1101/2020.08.14.240093 doi: 10.1101/2020.08.14.240093 id: cord-325473-hrdanbn1 author: Ghahremanpour, Mohammad M. title: Identification of 14 Known Drugs as Inhibitors of the Main Protease of SARS-CoV-2 date: 2020-08-28 words: 2915.0 sentences: 205.0 pages: flesch: 56.0 cache: ./cache/cord-325473-hrdanbn1.txt txt: ./txt/cord-325473-hrdanbn1.txt summary: 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 5 Thus, M pro is viewed as a promising target for anti SARS-CoV-2 drug design; it has been the focus of several studies since the pandemic has emerged. For instance, a molecular docking study suggested remdesivir as a potential therapeutic that could be used against SARS-CoV-2, 10 which was supported experimentally by an EC50 value of 23 μM in an infected-cell assay. Structural Basis for the Inhibition of SARS-CoV-2 Main Protease by Antineoplastic Drug Carmofur Crystal Structure of SARS-CoV-2 Main Protease Provides a Basis for Design of Improved α-Ketoamide Inhibitors Prediction of Novel Inhibitors of the Main Protease (M-pro) of SARS-CoV-2 through Consensus Docking and Drug Reposition Structure-based Design of Antiviral Drug Candidates Targeting the SARS-CoV-2 Main Protease Targeting the SARS-CoV-2 Main Protease to Repurpose Drugs for abstract: A consensus virtual screening protocol has been applied to ca. 2000 approved drugs to seek inhibitors of the main protease (Mpro) of SARS-CoV-2, the virus responsible for COVID-19. 42 drugs emerged as top candidates, and after visual analyses of the predicted structures of their complexes with Mpro, 17 were chosen for evaluation in a kinetic assay for Mpro inhibition. Remarkably 14 of the compounds at 100-μM concentration were found to reduce the enzymatic activity and 5 provided IC50 values below 40 μM: manidipine (4.8 μM), boceprevir (5.4 μM), lercanidipine (16.2 μM), bedaquiline (18.7 μM), and efonidipine (38.5 μM). Structural analyses reveal a common cloverleaf pattern for the binding of the active compounds to the P1, P1’, and P2 pockets of Mpro. Further study of the most active compounds in the context of COVID-19 therapy is warranted, while all of the active compounds may provide a foundation for lead optimization to deliver valuable chemotherapeutics to combat the pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/32869018/ doi: 10.1101/2020.08.28.271957 id: cord-287172-h8zoplkm author: Ghobrial, Moheb title: The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors date: 2020-10-21 words: 7020.0 sentences: 315.0 pages: flesch: 55.0 cache: ./cache/cord-287172-h8zoplkm.txt txt: ./txt/cord-287172-h8zoplkm.txt summary: To understand the potential mechanisms underlying SARS-CoV-2 tropism for brain vasculature, we constructed a molecular atlas of the expression patterns of SARS-CoV-2 viral entry-associated genes (receptors and proteases) and SARS-CoV-2 interaction partners in human (and mouse) adult and fetal brain as well as in multiple non-CNS tissues in single-cell RNA-sequencing data across various datasets. Notably, the top regulated pathways included inflammation, angiogenesis, coagulation, cell-extracellular matrix interaction, viral-host interaction, vascular metabolism, blood-brain-barrier permeability, and reactive oxygen species (ROS) in both the adult and the fetal brain endothelium ( Together, these data reveal that CTSB is highly expressed in various endothelial cell clusters of the fetal and adult human brain and that pathways downstream of CTSB might provide a suggestive explanation of some of the neurovascular symptoms observed in COVID-19 abstract: A large number of hospitalized COVID-19 patients show neurological symptoms such as ischemic- and hemorrhagic stroke as well as encephalitis, and SARS-CoV-2 can directly infect endothelial cells leading to endotheliitis across multiple vascular beds. These findings suggest an involvement of the brain- and peripheral vasculature in COVID-19, but the underlying molecular mechanisms remain obscure. To understand the potential mechanisms underlying SARS-CoV-2 tropism for brain vasculature, we constructed a molecular atlas of the expression patterns of SARS-CoV-2 viral entry-associated genes (receptors and proteases) and SARS-CoV-2 interaction partners in human (and mouse) adult and fetal brain as well as in multiple non-CNS tissues in single-cell RNA-sequencing data across various datasets. We observed a distinct expression pattern of the cathepsins B (CTSB) and -L (CTSL) - which are able to substitute for the ACE2 co-receptor TMPRSS2 - in the human vasculature with CTSB being mainly expressed in the brain vasculature and CTSL predominantly in the peripheral vasculature, and these observations were confirmed at the protein level in the Human Protein Atlas and using immunofluorescence stainings. This expression pattern of SARS-CoV-2 viral-entry associated proteases and SARS-CoV-2 interaction partners was also present in endothelial cells and microglia in the fetal brain, suggesting a developmentally established SARS-CoV-2 entry machinery in the human vasculature. At both the adult and fetal stages, we detected a distinct pattern of SARS-CoV-2 entry associated genes’ transcripts in brain vascular endothelial cells and microglia, providing a potential explanation for an inflammatory response in the brain endothelium upon SARS-CoV-2 infection. Moreover, CTSB was co-expressed in adult and fetal brain endothelial cells with genes and pathways involved in innate immunity and inflammation, angiogenesis, blood-brain-barrier permeability, vascular metabolism, and coagulation, providing a potential explanation for the role of brain endothelial cells in clinically observed (neuro)vascular symptoms in COVID-19 patients. Our study serves as a publicly available single-cell atlas of SARS-CoV-2 related entry factors and interaction partners in human and mouse brain endothelial- and perivascular cells, which can be employed for future studies in clinical samples of COVID-19 patients. url: https://doi.org/10.1101/2020.10.10.334664 doi: 10.1101/2020.10.10.334664 id: cord-310230-9wfb43gt author: Ghorbani, Mahdi title: Critical Sequence Hot-spots for Binding of nCOV-2019 to ACE2 as Evaluated by Molecular Simulations date: 2020-06-27 words: 3479.0 sentences: 220.0 pages: flesch: 56.0 cache: ./cache/cord-310230-9wfb43gt.txt txt: ./txt/cord-310230-9wfb43gt.txt summary: Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. 7 Based on the sequence similarity between RBD of nCOV-2019 and SARS-COV and also the tight binding between RBD of nCOV-2019 and ACE2, it is most probable that nCOV-2019 uses this receptor on human cells to gain entry into the body. The focus of this article is to elucidate the differences between the interface of SARS-COV and nCOV-2019 with ACE2 to understand with atomic resolution the interaction mechanism and hotspot residues at the RBD/ACE2 interface using long-timescale molecular dynamics (MD) simulation. The binding energetics between ACE2 and the RBD of SARS-COV, nCOV-2019 and all its mutant complexes were investigated by the MMPBSA method. Computational Simulations Reveal the Binding Dynamics between Human ACE2 and the Receptor Binding Domain of SARS-CoV-2 Spike Protein abstract: The novel coronavirus (nCOV-2019) outbreak has put the world on edge, causing millions of cases and hundreds of thousands of deaths all around the world, as of June 2020, let alone the societal and economic impacts of the crisis. The spike protein of nCOV-2019 resides on the virion’s surface mediating coronavirus entry into host cells by binding its receptor binding domain (RBD) to the host cell surface receptor protein, angiotensin converter enzyme (ACE2). Our goal is to provide a detailed structural mechanism of how nCOV-2019 recognizes and establishes contacts with ACE2 and its difference with an earlier coronavirus SARS-COV in 2002 via extensive molecular dynamics (MD) simulations. Numerous mutations have been identified in the RBD of nCOV-2019 strains isolated from humans in different parts of the world. In this study, we investigated the effect of these mutations as well as other Ala-scanning mutations on the stability of RBD/ACE2 complex. It is found that most of the naturally-occurring mutations to the RBD either strengthen or have the same binding affinity to ACE2 as the wild-type nCOV-2019. This may have implications for high human-to-human transmission of coronavirus in regions where these mutations have been found as well as any vaccine design endeavors since these mutations could act as antibody escape mutants. Furthermore, in-silico Ala-scanning and long-timescale MD simulations, highlight the crucial role of the residues at the interface of RBD and ACE2 that may be used as potential pharmacophores for any drug development endeavors. From an evolutional perspective, this study also identifies how the virus has evolved from its predecessor SARS-COV and how it could further evolve to become more infectious. url: https://www.ncbi.nlm.nih.gov/pubmed/32637962/ doi: 10.1101/2020.06.27.175448 id: cord-296981-tded20ih author: Gilmore, Kerry title: In vitro efficacy of Artemisinin-based treatments against SARS-CoV-2 date: 2020-10-05 words: 3162.0 sentences: 174.0 pages: flesch: 50.0 cache: ./cache/cord-296981-tded20ih.txt txt: ./txt/cord-296981-tded20ih.txt summary: We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). annua extracts, as well as pure artemisinin, artesunate, and artemether are active against SARS-CoV-2 in vitro. To initially screen whether extracts and pure artemisinin were active against SARS-CoV-2, their antiviral activity was tested by pretreating VeroE6 cells at different time points during 120 minutes with selected concentrations of the extracts or compounds prior to infection with the first European SARS-CoV-2 isolated in München (SARS-CoV-2/human/Germany/BavPat 1/2020). abstract: Effective and affordable treatments for patients suffering from coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are needed. We report in vitro efficacy of Artemisia annua extracts as well as artemisinin, artesunate, and artemether against SARS-CoV-2. The latter two are approved active pharmaceutical ingredients of anti-malarial drugs. Proof-of-concept for prophylactic efficacy of the extracts was obtained using a plaque-reduction assay in VeroE6 cells. Subsequent concentration-response studies using a high-throughput antiviral assay, based on immunostaining of SARS-CoV-2 spike glycoprotein, revealed that pretreatment and treatment with extracts, artemisinin, and artesunate inhibited SARS-CoV-2 infection of VeroE6 cells. In treatment assays, artesunate (50% effective concentration (EC50): 7 μg/mL) was more potent than the tested plant extracts (128-260 μg/mL) or artemisinin (151 μg/mL) and artemether (>179 μg/mL), while generally EC50 in pretreatment assays were slightly higher. The selectivity index (SI), calculated based on treatment and cell viability assays, was highest for artemisinin (54), and roughly equal for the extracts (5-10), artesunate (6) and artemether (<7). Similar results were obtained in human hepatoma Huh7.5 cells. Peak plasma concentrations of artesunate exceeding EC50 values can be achieved. Clinical studies are required to further evaluate the utility of these compounds as COVID-19 treatment. url: https://doi.org/10.1101/2020.10.05.326637 doi: 10.1101/2020.10.05.326637 id: cord-267115-6jqdi417 author: Giobbe, Giovanni Giuseppe title: SARS-CoV-2 infection and replication in human fetal and pediatric gastric organoids date: 2020-06-24 words: 8080.0 sentences: 408.0 pages: flesch: 47.0 cache: ./cache/cord-267115-6jqdi417.txt txt: ./txt/cord-267115-6jqdi417.txt summary: Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. Principal component analysis (PCA) showed smaller heterogeneity in the organoid groups derived at different stages of fetal and pediatric development with respect to the primary tissues analyzed at the same stages, which may also include some heterogeneity from the surrounding cells as a result of the isolation procedure (Fig. 3a) . In order to validate both fetal and pediatric gastric organoids as functional in vitro models of SARS-CoV-2 infection and replication, we optimized the culture condition for viral infection in a 3D system (Fig. 4a) . abstract: Coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global public health emergency. COVID-19 typically manifests as a respiratory illness but an increasing number of clinical reports describe gastrointestinal (GI) symptoms. This is particularly true in children in whom GI symptoms are frequent and viral shedding outlasts viral clearance from the respiratory system. By contrast, fetuses seem to be rarely affected by COVID-19, although the virus has been detected in placentas of affected women. These observations raise the question of whether the virus can infect and replicate within the stomach once ingested. Moreover, it is not yet clear whether active replication of SARS-CoV-2 is possible in the stomach of children or in fetuses at different developmental stages. Here we show the novel derivation of fetal gastric organoids from 8-21 post-conception week (PCW) fetuses, and from pediatric biopsies, to be used as an in vitro model for SARS-CoV-2 gastric infection. Gastric organoids recapitulate human stomach with linear increase of gastric mucin 5AC along developmental stages, and expression of gastric markers pepsinogen, somatostatin, gastrin and chromogranin A. In order to investigate SARS-CoV-2 infection with minimal perturbation and under steady-state conditions, we induced a reversed polarity in the gastric organoids (RP-GOs) in suspension. In this condition of exposed apical polarity, the virus can easily access viral receptor angiotensin-converting enzyme 2 (ACE2). The pediatric RP-GOs are fully susceptible to infection with SARS-CoV-2, where viral nucleoprotein is expressed in cells undergoing programmed cell death, while the efficiency of infection is significantly lower in fetal organoids. The RP-GOs derived from pediatric patients show sustained robust viral replication of SARS-CoV-2, compared with organoids derived from fetal stomachs. Transcriptomic analysis shows a moderate innate antiviral response and the lack of differentially expressed genes belonging to the interferon family. Collectively, we established the first expandable human gastric organoid culture across fetal developmental stages, and we support the hypothesis that fetal tissue seems to be less susceptible to SARS-CoV-2 infection, especially in early stages of development. However, the virus can efficiently infect gastric epithelium in pediatric patients, suggesting that the stomach might have an active role in fecal-oral transmission of SARS-CoV-2. url: https://doi.org/10.1101/2020.06.24.167049 doi: 10.1101/2020.06.24.167049 id: cord-350286-n7ylgqfu author: Giri, Rajanish title: When Darkness Becomes a Ray of Light in the Dark Times: Understanding the COVID-19 via the Comparative Analysis of the Dark Proteomes of SARS-CoV-2, Human SARS and Bat SARS-Like Coronaviruses date: 2020-04-03 words: 15827.0 sentences: 874.0 pages: flesch: 56.0 cache: ./cache/cord-350286-n7ylgqfu.txt txt: ./txt/cord-350286-n7ylgqfu.txt summary: The results of this analysis are summarized in Table 2 , which clearly shows that most of the SARS-CoV-2 proteins contain at least one MoRF, indicating that disorder does play an important role in the functionality of these viral proteins. As it follows from Figure 3 , these cleavage sites are located within the IDPRs. In Human SARS CoV S protein, fusion peptide (residues 770-788) is located within a flexible region, is characterized by the mean disorder score of 0.232±0.053. Global analysis of intrinsic disorder in the replicase polyprotein 1ab Table 3 represents the PPID mean scores of 15 non-structural proteins (Nsps) derived from the Replicase polyprotein 1ab in SARS-CoV-2, Human SARS CoV, and Bat CoV. Similar to many other non-structural proteins of coronaviruses, Nsp15s from SARS-CoV-2, Human SARS, and Bat CoV are predicted to possess multiple flexible regions but contain virtually no IDPRs (see Figures 32A, 32B, and 32C) . abstract: Recently emerged coronavirus designated as SARS-CoV-2 (also known as 2019 novel coronavirus (2019-nCoV) or Wuhan coronavirus) is a causative agent of coronavirus disease 2019 (COVID-19), which is rapidly spreading throughout the world now. More than 9,00,000 cases of SARS-CoV-2 infection and more than 47,000 COVID-19-associated mortalities have been reported worldwide till the writing of this article, and these numbers are increasing every passing hour. World Health Organization (WHO) has declared the SARS-CoV-2 spread as a global public health emergency and admitted that the COVID-19 is a pandemic now. The multiple sequence alignment data correlated with the already published reports on the SARS-CoV-2 evolution and indicated that this virus is closely related to the bat Severe Acute Respiratory Syndrome-like coronavirus (bat SARS-like CoV) and the well-studied Human SARS coronavirus (SARS CoV). The disordered regions in viral proteins are associated with the viral infectivity and pathogenicity. Therefore, in this study, we have exploited a set of complementary computational approaches to examine the dark proteomes of SARS-CoV-2, bat SARS-like, and human SARS CoVs by analysing the prevalence of intrinsic disorder in their proteins. According to our findings, SARS-CoV-2 proteome contains very significant levels of structural order. In fact, except for Nucleocapsid, Nsp8, and ORF6, the vast majority of SARS-CoV-2 proteins are mostly ordered proteins containing less intrinsically disordered protein regions (IDPRs). However, IDPRs found in SARS-CoV-2 proteins are functionally important. For example, cleavage sites in its replicase 1ab polyprotein are found to be highly disordered, and almost all SARS-CoV-2 proteins were shown to contain molecular recognition features (MoRFs), which are intrinsic disorder-based protein-protein interaction sites that are commonly utilized by proteins for interaction with specific partners. The results of our extensive investigation of the dark side of the SARS-CoV-2 proteome will have important implications for the structural and non-structural biology of SARS or SARS-like coronaviruses. Significance The infection caused by a novel coronavirus (SARS-CoV-2) that causes severe respiratory disease with pneumonia-like symptoms in humans is responsible for the current COVID-19 pandemic. No in-depth information on structures and functions of SARS-CoV-2 proteins is currently available in the public domain, and no effective anti-viral drugs and/or vaccines are designed for the treatment of this infection. Our study provides the first comparative analysis of the order- and disorder-based features of the SARS-CoV-2 proteome relative to human SARS and bat CoV that may be useful for structure-based drug discovery. url: https://doi.org/10.1101/2020.03.13.990598 doi: 10.1101/2020.03.13.990598 id: cord-103358-1hbw3yo3 author: Gisbert-Muñoz, Sandra title: MULTIMAP: Multilingual picture naming test for mapping eloquent areas during awake surgeries date: 2020-06-08 words: 4348.0 sentences: 196.0 pages: flesch: 45.0 cache: ./cache/cord-103358-1hbw3yo3.txt txt: ./txt/cord-103358-1hbw3yo3.txt summary: Although the use of object naming tasks is widespread across surgical teams in many different geographical locations, heterogeneity in the stimuli selection criteria of previous batteries (i.e., differences in picture size, color, image quality, name agreement), in addition to the use of morphologically and typologically different languages across different studies (see supplementary material for a table review), has greatly hindered the comparison and generalization of results. Notably, direct cortical stimulation studies also show this double dissociation when object and action naming tasks are used, and allow for the identification of distinct territories in frontal and temporal brain areas in which stimulation selectively impairs verb or noun production (Corina et al., 2005; Crepaldi, Berlingeri, Paulesu, & Luzzatti, 2011; Lubrano et al., 2014; J. To address this need, we developed the MULTIMAP test, a multilingual picture naming task including both objects and actions for mapping eloquent areas during awake brain surgery. abstract: Picture naming tasks are currently the gold standard for identifying and preserving language-related areas during awake brain surgery. With multilingual populations increasing worldwide, patients frequently need to be tested in more than one language. There is still no reliable testing instrument, as the available batteries have been developed for specific languages. Heterogeneity in the selection criteria for stimuli leads to differences, for example, in the size, color, image quality, and even names associated with pictures, making direct cross-linguistic comparisons difficult. Here we present MULTIMAP, a new multilingual picture naming test for mapping eloquent areas during awake brain surgery. Recognizing that the distinction between nouns and verbs is necessary for detailed and precise language mapping, MULTIMAP consists of a database of 218 standardized color pictures representing both objects and actions. These images have been tested for name agreement with speakers of Spanish, Basque, Catalan, Italian, French, English, Mandarin Chinese, and Arabic, and have been controlled for relevant linguistic features in cross-language combinations. The MULTIMAP test for objects and verbs represents an alternative to the DO 80 monolingual pictorial set currently used in language mapping, providing an open-source, standardized set of up-to-date pictures, where relevant linguistic variables across several languages have been taken into account in picture creation and selection. url: https://doi.org/10.1101/2020.02.20.957282 doi: 10.1101/2020.02.20.957282 id: cord-346670-34wfy52f author: Gobeil, Sophie M-C. title: D614G mutation alters SARS-CoV-2 spike conformational dynamics and protease cleavage susceptibility at the S1/S2 junction date: 2020-10-12 words: 7065.0 sentences: 359.0 pages: flesch: 57.0 cache: ./cache/cord-346670-34wfy52f.txt txt: ./txt/cord-346670-34wfy52f.txt summary: Most structures of the SARS-CoV-2 S ectodomain currently available include two mutations, one to disrupt the furin cleavage site (RRAR to GSAS = S-GSAS), and a double proline mutation (PP) of residues 986-987, designed to prevent conformational change to the post-fusion state (Wrapp et al., 2020) . While the SARS-CoV-2 S ectodomain construct that includes mutations of residues K986 and V987, between the HR1 and CH subdomains (S2 domain), to prolines (PP) (named S-GSAS/PP in this study) (Figure 1 ) is widely used in the field, the origin of this PP construct was based upon the stabilization of the pre-fusion conformation of other coronavirus spikes (Pallesen et al., 2017; Walls et al., 2020; Wrapp et al., 2020) . Similar to observations made with the S-GSAS/D614G S ectodomain structure, the RBD up/down motion in the furin-cleaved G614 S ectodomain was associated with a movement in the SD1 domain and in the region of the RBD-to-NTD linker that joined the SD1 b sheet ( Figure 7C, S8B) . abstract: The SARS-CoV-2 spike (S) protein is the target of vaccine design efforts to end the COVID-19 pandemic. Despite a low mutation rate, isolates with the D614G substitution in the S protein appeared early during the pandemic, and are now the dominant form worldwide. Here, we analyze the D614G mutation in the context of a soluble S ectodomain construct. Cryo-EM structures, antigenicity and proteolysis experiments suggest altered conformational dynamics resulting in enhanced furin cleavage efficiency of the G614 variant. Furthermore, furin cleavage altered the conformational dynamics of the Receptor Binding Domains (RBD) in the G614 S ectodomain, demonstrating an allosteric effect on the RBD dynamics triggered by changes in the SD2 region, that harbors residue 614 and the furin cleavage site. Our results elucidate SARS-CoV-2 spike conformational dynamics and allostery, and have implications for vaccine design. Highlights SARS-CoV-2 S ectodomains with or without the K986P, V987P mutations have similar structures, antigenicity and stability. The D614G mutation alters S protein conformational dynamics. D614G enhances protease cleavage susceptibility at the S protein furin cleavage site. Cryo-EM structures reveal allosteric effect of changes at the S1/S2 junction on RBD dynamics. url: https://doi.org/10.1101/2020.10.11.335299 doi: 10.1101/2020.10.11.335299 id: cord-332539-v1bfm57x author: Gohl, Daryl M. title: A Rapid, Cost-Effective Tailed Amplicon Method for Sequencing SARS-CoV-2 date: 2020-05-11 words: 5048.0 sentences: 246.0 pages: flesch: 55.0 cache: ./cache/cord-332539-v1bfm57x.txt txt: ./txt/cord-332539-v1bfm57x.txt summary: Several variants of the ARTIC protocol exist in which the pooled SARS-CoV-2 amplicons from a sample are taken through a NGS library preparation protocol (using either ligation or tagmentation-based approaches) in which sample-specific barcodes are added, and are then sequenced using either short-read (Illumina) or long-read (Oxford Nanopore, PacBio) technologies. We sequenced these samples using Illumina''s Nextera DNA Flex Enrichment protocol using a respiratory virus oligo panel containing probes for SARS-CoV-2, the ARTIC v3 tiled primers, and a novel tailed amplicon method designed to reduce cost and streamline the preparation of SARS-CoV-2 sequencing libraries. For the Illumina DNA Flex Enrichment protocol, SARS-CoV-2 genome coverage was more complete for samples with lower N1 and N2 Cts (ranging from ~20-30) at comparable read depths and coverage thresholds than with amplicon approaches, similar to the BEI WA isolate data ( Figure 3C , Supplemental Figure S2 -S3). abstract: The global COVID-19 pandemic has led to an urgent need for scalable methods for clinical diagnostics and viral tracking. Next generation sequencing technologies have enabled large-scale genomic surveillance of SARS-CoV-2 as thousands of isolates are being sequenced around the world and deposited in public data repositories. A number of methods using both short- and long-read technologies are currently being applied for SARS-CoV-2 sequencing, including amplicon approaches, metagenomic methods, and sequence capture or enrichment methods. Given the small genome size, the ability to sequence SARS-CoV-2 at scale is limited by the cost and labor associated with making sequencing libraries. Here we describe a low-cost, streamlined, all amplicon-based method for sequencing SARS-CoV-2, which bypasses costly and time-consuming library preparation steps. We benchmark this tailed amplicon method against both the ARTIC amplicon protocol and sequence capture approaches and show that an optimized tailed amplicon approach achieves comparable amplicon balance, coverage metrics, and variant calls to the ARTIC v3 approach and represents a cost-effective and highly scalable method for SARS-CoV-2 sequencing. url: https://doi.org/10.1101/2020.05.11.088724 doi: 10.1101/2020.05.11.088724 id: cord-351011-v4zmksio author: Golden, Joseph W. title: Human angiotensin-converting enzyme 2 transgenic mice infected with SARS-CoV-2 develop severe and fatal respiratory disease date: 2020-07-09 words: 4650.0 sentences: 268.0 pages: flesch: 52.0 cache: ./cache/cord-351011-v4zmksio.txt txt: ./txt/cord-351011-v4zmksio.txt summary: In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. In comparison with the normal lung architecture in uninfected control animals, infected mice necropsied on day 3, and those succumbing to disease on days 5-11, had varying levels of lung injury including area of lung consolidation characterized by inflammation/expansion of 145 alveolar septa with fibrin, edema and mononuclear leukocytes and infiltration of vessel walls by numerous mononuclear leukocytes (Fig 3A, Fig S4, and Table S1 ). Importantly, in our study some animals at the lower dose survived infection despite significant Infection of K18-hACE2 mice by SARS-CoV-2 produces a disease similar to that observed in acute human cases, with development of an acute lung injury associated with edema, production 285 of inflammatory cytokines and the accumulation of mononuclear cells in the lung. abstract: The emergence of SARS-CoV-2 has created an international health crisis. Small animal models mirroring SARS-CoV-2 human disease are essential for medical countermeasure (MCM) development. Mice are refractory to SARS-CoV-2 infection due to low affinity binding to the murine angiotensin-converting enzyme 2 (ACE2) protein. Here we evaluated the pathogenesis of SARS-CoV-2 in male and female mice expressing the human ACE2 gene under the control of the keratin 18 promotor. In contrast to non-transgenic mice, intranasal exposure of K18-hACE2 animals to two different doses of SARS-CoV-2 resulted in acute disease including weight loss, lung injury, brain infection and lethality. Vasculitis was the most prominent finding in the lungs of infected mice. Transcriptomic analysis from lungs of infected animals revealed increases in transcripts involved in lung injury and inflammatory cytokines. In the lower dose challenge groups, there was a survival advantage in the female mice with 60% surviving infection whereas all male mice succumbed to disease. Male mice that succumbed to disease had higher levels of inflammatory transcripts compared to female mice. This is the first highly lethal murine infection model for SARS-CoV-2. The K18-hACE2 murine model will be valuable for the study of SARS-CoV-2 pathogenesis and the assessment of MCMs. url: https://doi.org/10.1101/2020.07.09.195230 doi: 10.1101/2020.07.09.195230 id: cord-255325-tl5fm2yu author: Goletic, Teufik title: Phylogenetic pattern of SARS-CoV-2 from COVID-19 patients from Bosnia and Herzegovina: lessons learned to optimize future molecular and epidemiological approaches date: 2020-06-19 words: 1726.0 sentences: 95.0 pages: flesch: 49.0 cache: ./cache/cord-255325-tl5fm2yu.txt txt: ./txt/cord-255325-tl5fm2yu.txt summary: Objectives of this research were: To share obtained sequences of the complete genome of SARS-CoV-2 strains from clinical samples of BiH patients diagnosed with COVID-19, and To contribute to the understanding of the interaction of molecular and classical epidemiology findings of COVID 19 in BH and the whole region and give recommendations for the improvement of prevention and future measures. Livno and Banja Luka samples WGS was performed according to the ARTIC amplicon sequencing protocol for MinION for nCoV-2019, which uses two primer pools to generate the sequence, as described elsewhere [7] . The constructed phylogenetic tree in Figure 2 indicates probable multiple independent introduction events as reflected by clustering of each single BiH sequence in a separate cluster, highlighted with red (Livno, EPI_ISL_462753), green (Banja Luka, EPI_ISL_462990), blue (Sarajevo, EPI_ISL_467300) and purple (Tuzla, EPI_ISL_463893). abstract: Whole Genome Sequence of four samples from COVID-19 outbreaks was done in two laboratories in Bosnia and Herzegovina (Veterinary Faculty Sarajevo and Alea Genetic Center). All four BiH sequences cluster mainly with European ones (Italy, Austria, France, Sweden, Cyprus, England). The constructed phylogenetic tree indicates probable multiple independent introduction events. The success of future containment measures concernig new introductions will be highly challenging for country due to the significant proportion of BH population living abroad. url: https://doi.org/10.1101/2020.06.19.160606 doi: 10.1101/2020.06.19.160606 id: cord-102886-oo7q05ml author: Gomes, Fabio M. title: “Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes” date: 2020-09-10 words: 1963.0 sentences: 116.0 pages: flesch: 45.0 cache: ./cache/cord-102886-oo7q05ml.txt txt: ./txt/cord-102886-oo7q05ml.txt summary: title: "Proliferation of DBLOX Peroxidase-Expressing Oenocytes Maintains Innate Immune Memory in Primed Mosquitoes" Immune priming in Anopheles gambiae mosquitoes following infection with Plasmodium parasites is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4 bound to Evokin, a lipid carrier. We provide direct evidence that modifications mediated by the histone acetyltransferase AgTip60 (AGAP01539) are essential for sustained oenocyte proliferation, HDF synthesis and immune priming. We propose that oenocytes function as a population of "memory" cells that continuously release lipoxin to orchestrate and maintain a broad, systemic and long-lasting state of enhanced immune surveillance. We recently showed that two heme peroxidases, HPX7 and HPX8, are necessary for midgut PGE 2 synthesis and are essential to establish immune priming in response to Plasmodium infection (8) . These cells express high levels of DBLOX and their proliferation is essential for HDF synthesis and to maintain the priming response. abstract: Immune priming in Anopheles gambiae mosquitoes following infection with Plasmodium parasites is mediated by the systemic release of a hemocyte differentiation factor (HDF), a complex of lipoxin A4 bound to Evokin, a lipid carrier. HDF increases the proportion of circulating granulocytes and enhances mosquito cellular immunity. We found that Evokin is constitutively produced by hemocytes and fat-body cells, but expression increases in response to infection. Insects synthesize lipoxins, but lack lipoxygenases. Here, we show that the Double Peroxidase (DBLOX) enzyme, present in insects but not in vertebrates, is essential for HDF synthesis. DBLOX is highly expressed in oenocytes in the fat body tissue, and these cells proliferate in response to Plasmodium challenge. We provide direct evidence that modifications mediated by the histone acetyltransferase AgTip60 (AGAP01539) are essential for sustained oenocyte proliferation, HDF synthesis and immune priming. We propose that oenocytes function as a population of “memory” cells that continuously release lipoxin to orchestrate and maintain a broad, systemic and long-lasting state of enhanced immune surveillance. url: https://doi.org/10.1101/2020.09.09.290312 doi: 10.1101/2020.09.09.290312 id: cord-102406-9gnbe3n1 author: González-Arias, Fabio title: Scalable Analysis of Authentic Viral Envelopes on FRONTERA date: 2020-07-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Enveloped viruses infect host cells via fusion of their viral envelope with the plasma membrane. Upon cell entry, viruses gain access to all the macromolecular machinery necessary to replicate, assemble, and bud their progeny from the infected cell. By employing molecular dynamics simulations to characterize the dynamical and chemical-physical properties of viral envelopes, researchers can gain insights into key determinants of viral infection and propagation. Here, the Frontera supercomputer is leveraged for large-scale analysis of authentic viral envelopes, whose lipid compositions are complex and realistic. VMD with support for MPI is employed on the massive parallel computer to overcome previous computational limitations and enable investigation into virus biology at an unprecedented scale. The modeling and analysis techniques applied to authentic viral envelopes at two levels of particle resolution are broadly applicable to the study of other viruses, including the novel coronavirus that causes COVID-19. A framework for carrying out scalable analysis of multi-million particle MD simulation trajectories on Frontera is presented, expanding the the utility of the machine in humanity’s ongoing fight against infectious disease. url: https://doi.org/10.1101/2020.07.05.188367 doi: 10.1101/2020.07.05.188367 id: cord-356090-oj3d9ail author: Gorgun, D. title: Binding Mode of SARS-CoV2 Fusion Peptide to Human Cellular Membrane date: 2020-10-27 words: 6065.0 sentences: 277.0 pages: flesch: 51.0 cache: ./cache/cord-356090-oj3d9ail.txt txt: ./txt/cord-356090-oj3d9ail.txt summary: Here, we use an array of molecular dynamics (MD) simulations taking advantage of the Highly Mobile Membrane Mimetic (HMMM) model, to investigate the interaction of the SARS-CoV2 FP with a lipid bilayer representing mammalian cellular membranes at an atomic level, and to characterize the membrane-bound form of the peptide. Taken into account the sequence conservation among the viral FPs and the results of mutagenesis studies establishing the role of specific residues in the helical portion of the FP in membrane association, we propose that the helix-binding mode represents more closely the biologically relevant form. In this study, using molecular dynamics simulations, we describe how the fusion peptide from the SARS-CoV2 virus binds human cellular membranes and characterize, at an atomic level, lipid-protein interactions important for the stability of the bound state. In this study, using a large set of simulations, we describe how the SARS-CoV2 FP binds mammalian cellular membranes and characterize, at atomic details, lipid-protein interactions important for the stability of the bound state. abstract: Infection of human cells by the SARS-CoV2 relies on its binding to a specific receptor and subsequent fusion of the viral and host cell membranes. The fusion peptide (FP), a short peptide segment in the spike protein, plays a central role in the initial penetration of the virus into the host cell membrane, followed by the fusion of the two membranes. Here, we use an array of molecular dynamics (MD) simulations taking advantage of the Highly Mobile Membrane Mimetic (HMMM) model, to investigate the interaction of the SARS-CoV2 FP with a lipid bilayer representing mammalian cellular membranes at an atomic level, and to characterize the membrane-bound form of the peptide. Six independent systems were generated by changing the initial positioning and orientation of the FP with respect to the membrane, and each system was simulated in five independent replicas. In 60% of the simulations, the FP reaches a stable, membrane-bound configuration where the peptide deeply penetrated into the membrane. Clustering of the results reveals two major membrane binding modes, the helix-binding mode and the loop-binding mode. Taken into account the sequence conservation among the viral FPs and the results of mutagenesis studies establishing the role of specific residues in the helical portion of the FP in membrane association, we propose that the helix-binding mode represents more closely the biologically relevant form. In the helix-binding mode, the helix is stabilized in an oblique angle with respect to the membrane with its N-terminus tilted towards the membrane core. Analysis of the FP-lipid interactions shows the involvement of specific residues of the helix in membrane binding previously described as the fusion active core residues. Taken together, the results shed light on a key step involved in SARS-CoV2 infection with potential implications in designing novel inhibitors. SIGNIFICANCE A key step in cellular infection by the SARS-CoV2 virus is its attachment to and penetration into the plasma membrane of human cells. These processes hinge upon the membrane interaction of the viral fusion peptide, a segment exposed by the spike protein upon its conformational changes after encountering the host cell. In this study, using molecular dynamics simulations, we describe how the fusion peptide from the SARS-CoV2 virus binds human cellular membranes and characterize, at an atomic level, lipid-protein interactions important for the stability of the bound state. url: https://doi.org/10.1101/2020.10.27.357350 doi: 10.1101/2020.10.27.357350 id: cord-331680-qlzhtxs0 author: Goryachev, A.N. title: Potential Opportunity of Antisense Therapy of COVID-19 on an in Vitro Model date: 2020-11-03 words: 4106.0 sentences: 200.0 pages: flesch: 51.0 cache: ./cache/cord-331680-qlzhtxs0.txt txt: ./txt/cord-331680-qlzhtxs0.txt summary: In accordance with the purpose of the study, the following tasks were set: -to select the nucleotide sequence of the virus that is supposed to be inhibited, -to carry out the synthesis of oligonucleotide, -to determine cytotoxicity and antiviral activity in an in vitro experiment on cell culture. The assessment of antiviral activity of the drug in addition to cytopathic action was also taken into account by reducing the infectious titer of the virus in the culture of Vero cells E6 according to PCR RNA SARS-CoV-2, determined by the threshold of the number of reaction cycles (cycle treshold, Ct) in various dilutions of the study drug. Determination of the antiviral efficacy of the antisense oligonucleotide according to the treatment scheme (administration of the drug 24 hours after infection) was taken into account by the decrease in the infectious titer of the virus in the culture of Vero E6 cells by the cytopathic effect. abstract: Data on potential effectiveness and prospects of treatment of new coronavirus infection of COVID-19 caused by virus SARS-CoV-2 with the help of antisense oligonucleotides acting against RNA of virus on an in vitro model are given. The ability of antisense oligonucleotides to suppress viral replication in diseases caused by coronaviruses using the example of SARS and MERS is shown. The identity of the initial regulatory section of RNA of various coronaviruses was found within 50 - 100 nucleotides from the 5’-end, which allows using antisense suppression of this RNA fragment. A new RNA fragment of the virus present in all samples of coronovirus SARS-CoV-2 has been identified, the suppression of which with the help of an antisense oligonucleotide can be effective in the treatment of COVID-19. The study of the synthesized antisense oligonucleotide 5’ - AGCCGAGTGACAGCC ACACAG, complementary to the selected virus RNA sequence, was carried out. The low toxicity of the preparations of this group in the cell culture study and the ability to reduce viral load at high doses according to real time-PCR data are shown. The cytopathogenic dose exceeds 2 mg / ml. At a dosage of 1 mg / ml, viral replication is reduced by 5-13 times. Conclusions are made about the prospects of this direction and the feasibility of using the inhalation way of drug administration into the body. url: https://doi.org/10.1101/2020.11.02.363598 doi: 10.1101/2020.11.02.363598 id: cord-351321-6d2mn5ok author: Gouveia, Duarte title: Proteotyping SARS-CoV-2 virus from nasopharyngeal swabs: a proof-of-concept focused on a 3 min mass spectrometry window date: 2020-06-19 words: 6241.0 sentences: 294.0 pages: flesch: 52.0 cache: ./cache/cord-351321-6d2mn5ok.txt txt: ./txt/cord-351321-6d2mn5ok.txt summary: Simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC-MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. By using a short LC gradient focusing on the region of interest identified in our previous study, we tested the detection of the virus in samples containing different quantities of viral peptides, as well as COVID-19 clinical samples, paving the way for the development of time-efficient viral diagnostic tests based on an alternative platform. To assess the performance of shotgun MS-based proteomics in detecting SARS-CoV-2 peptides in a background matrix consisting of nasopharyngeal swab protein material, we experimentally created tryptic peptidomes from i) a purified virus solution obtained from Vero E6 cells infected with a SARS-CoV-2 reference strain, and ii) nasopharyngeal swabs obtained from two healthy volunteers (Figure 1) . Simili swabs containing specific quantities of SARS-CoV-2 virus and the equivalent of 8.4% of the nasal matrix protein material collected during sampling were analysed by MS/MS with a short gradient. abstract: Rapid but yet sensitive, specific and high-throughput detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in clinical samples is key to diagnose infected people and to better control the spread of the virus. Alternative methodologies to PCR and immunodiagnostic that would not require specific reagents are worth to investigate not only for fighting the COVID-19 pandemic, but also to detect other emergent pathogenic threats. Here, we propose the use of tandem mass spectrometry to detect SARS-CoV-2 marker peptides in nasopharyngeal swabs. We documented that the signal from the microbiota present in such samples is low and can be overlooked when interpreting shotgun proteomic data acquired on a restricted window of the peptidome landscape. Simili nasopharyngeal swabs spiked with different quantities of purified SARS-CoV-2 viral material were used to develop a nanoLC-MS/MS acquisition method, which was then successfully applied on COVID-19 clinical samples. We argue that peptides ADETQALPQR and GFYAQGSR from the nucleocapsid protein are of utmost interest as their signal is intense and their elution can be obtained within a 3 min window in the tested conditions. These results pave the way for the development of time-efficient viral diagnostic tests based on mass spectrometry. url: https://doi.org/10.1101/2020.06.19.161000 doi: 10.1101/2020.06.19.161000 id: cord-277487-jgbjxgh1 author: Graham, Simon P. title: Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19 date: 2020-06-20 words: 5057.0 sentences: 242.0 pages: flesch: 53.0 cache: ./cache/cord-277487-jgbjxgh1.txt txt: ./txt/cord-277487-jgbjxgh1.txt summary: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. Analysis of SARS-CoV-2 S protein-specific murine splenocyte responses by IFNγ ELISpot assay showed no statistically significant difference between the prime-only and primeboost vaccination regimens, in either strain of mouse ( Figure 1A ). IFN-γ ELISpot analysis of porcine peripheral blood mononuclear cells (PBMC) showed responses on 42 dpv (2 weeks after boost) that were significantly greater in the prime-boost pigs compared to prime-only animals (p < 0.05; Figure 1C ). : SARS-CoV-2 S protein-specific antibody responses following ChAdOx1 nCoV-19 primeonly and prime-boost vaccination regimens in mice and pigs. abstract: Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres. url: https://doi.org/10.1101/2020.06.20.159715 doi: 10.1101/2020.06.20.159715 id: cord-299737-r34d0rx7 author: Grant, Paul R title: Extraction-free COVID-19 (SARS-CoV-2) diagnosis by RT-PCR to increase capacity for national testing programmes during a pandemic date: 2020-04-08 words: 1383.0 sentences: 78.0 pages: flesch: 63.0 cache: ./cache/cord-299737-r34d0rx7.txt txt: ./txt/cord-299737-r34d0rx7.txt summary: The standard molecular diagnostic test is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). We have developed a simplified qRT-PCR assay that removes the need for an RNA extraction process and can be run on a real-time thermal cycler. The standard molecular diagnostic test for this virus is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). Using the same primers and probes, we have now developed a qRT-PCR that can be run on a real-time thermal cycler without the need for an RNA extraction process. Direct addition of samples to the qRT-PCR without extraction with a diagnostic sensitivity of 98.0%, specificity of 100% and accuracy of 98.8% compared to the method on the Panther Fusion. Many laboratories use real-time thermal cyclers, so this method can be used to increase national screening capacity without the need for other specialized equipment or RNA extraction reagents. abstract: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus disease 2019 (COVID-19), a respiratory tract infection. The standard molecular diagnostic test is a multistep process involving viral RNA extraction and real-time quantitative reverse transcriptase PCR (qRT-PCR). Laboratories across the globe face constraints on equipment and reagents during the COVID-19 pandemic. We have developed a simplified qRT-PCR assay that removes the need for an RNA extraction process and can be run on a real-time thermal cycler. The assay uses custom primers and probes, and maintains diagnostic sensitivity within 98.0% compared to the assay run on a high-throughput, random-access automated platform, the Panther Fusion (Hologic). This assay can be used to increase capacity for COVID-19 testing for national programmes worldwide. url: https://doi.org/10.1101/2020.04.06.028316 doi: 10.1101/2020.04.06.028316 id: cord-304356-jyp9gjh9 author: Grant, Rogan A. title: Alveolitis in severe SARS-CoV-2 pneumonia is driven by self-sustaining circuits between infected alveolar macrophages and T cells date: 2020-08-05 words: 7453.0 sentences: 427.0 pages: flesch: 44.0 cache: ./cache/cord-304356-jyp9gjh9.txt txt: ./txt/cord-304356-jyp9gjh9.txt summary: We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. b. Sankey diagram illustrating relationship between number of BAL samples from participants with COVID-19, other viral pneumonia, non-viral pneumonia (other pneumonia) and non-pneumonia controls 1) enrolled in the SCRIPT study (534 samples), 2) analyzed via flow cytometry (344 samples), 3) bulk RNA-seq on flow-sorted alveolar macrophages (243 samples) and 4) single-cell RNA-seq (6 samples). To define the immune cell profile over the course of severe SARS-CoV-2-induced pneumonia, we analyzed 116 samples from 61 patients with confirmed COVID-19 in our cohort. As our analysis of transcriptomic data from alveolar macrophages suggested that SARS-CoV-2 pneumonia is uniquely associated with the activation of pathways induced by interferons, we looked for the expression of type I interferons in our single cell dataset. abstract: Some patients infected with Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) develop severe pneumonia and the acute respiratory distress syndrome (ARDS) [1]. Distinct clinical features in these patients have led to speculation that the immune response to virus in the SARS-CoV-2-infected alveolus differs from other types of pneumonia [2]. We collected bronchoalveolar lavage fluid samples from 86 patients with SARS-CoV-2-induced respiratory failure and 252 patients with known or suspected pneumonia from other pathogens and subjected them to flow cytometry and bulk transcriptomic profiling. We performed single cell RNA-Seq in 5 bronchoalveolar lavage fluid samples collected from patients with severe COVID-19 within 48 hours of intubation. In the majority of patients with SARS-CoV-2 infection at the onset of mechanical ventilation, the alveolar space is persistently enriched in alveolar macrophages and T cells without neutrophilia. Bulk and single cell transcriptomic profiling suggest SARS-CoV-2 infects alveolar macrophages that respond by recruiting T cells. These T cells release interferon-gamma to induce inflammatory cytokine release from alveolar macrophages and further promote T cell recruitment. Our results suggest SARS-CoV-2 causes a slowly unfolding, spatially-limited alveolitis in which alveolar macrophages harboring SARS-CoV-2 transcripts and T cells form a positive feedback loop that drives progressive alveolar inflammation. This manuscript is accompanied by an online resource: https://www.nupulmonary.org/covid-19/ One sentence summary SARS-CoV-2-infected alveolar macrophages form positive feedback loops with T cells in patients with severe COVID-19. url: https://doi.org/10.1101/2020.08.05.238188 doi: 10.1101/2020.08.05.238188 id: cord-255515-7se14455 author: Graudenzi, Alex title: Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity date: 2020-07-06 words: 8275.0 sentences: 450.0 pages: flesch: 53.0 cache: ./cache/cord-255515-7se14455.txt txt: ./txt/cord-255515-7se14455.txt summary: To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, our analysis allowed to identify three non-overlapping mutational signatures, i.e., specific distributions of nucleotide substitutions, which are observed in distinct clusters of samples in a mutually exclusive fashion, suggesting the presence of host-related mutational processes. Finally, the analysis of homoplasies, i.e., (low-frequency) variants shared across distinct viral lineages and unlikely due to infection events, demonstrate that a high number of mutations can independently emerge in multiple samples, due to mutational hotspots often related to signatures or, possibly, to positive (functional) selection. abstract: To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, the deconvolution of the entire set of intra-host variants reveals the existence of mutually exclusive viral mutational signatures, which prove that distinct hosts differently respond to SARS-CoV-2 infections. In particular, two signatures are likely ruled by APOBEC and Reactive Oxygen Species (ROS), which induce hypermutation in a significant number of samples, and appear to be affected by severe purifying selection. Conversely, several mutations linked to low-rate mutational processes appear to transit to clonality in the population, eventually leading to the definition of new viral genotypes and to an increase of overall genomic diversity. Finally, we demonstrate that a high number of variants are observed in samples associated to independent lineages, likely due to signature-related mutational hotspots or to positive selection. url: https://doi.org/10.1101/2020.07.06.189944 doi: 10.1101/2020.07.06.189944 id: cord-326380-9ecsp66y author: Griesemer, Sara B title: Assessment of sample pooling for clinical SARS-CoV-2 testing date: 2020-05-27 words: 2234.0 sentences: 113.0 pages: flesch: 52.0 cache: ./cache/cord-326380-9ecsp66y.txt txt: ./txt/cord-326380-9ecsp66y.txt summary: The greatest concern with this approach in a clinical setting is the potential for reduced sensitivity, particularly the risk of false negative results when weak positive samples are pooled. To investigate this possibility, detection rates in pooled samples were evaluated, with extensive assessment of pools containing weak positive specimens. Additionally, the percentage of positive samples at different viral loads, as assessed by Ct value, was reviewed across nine weeks of the pandemic, to determine if these weak positive specimens comprise a significant component of total tested specimens and whether the proportion has changed over the course of the pandemic. In contrast, for weak positive specimens in VTM transport media, nine-sample pools caused multiple replicates to return negative results. We then sought to assess what component of the total specimens tested are comprised of these weak positive specimens, to evaluate how much of an impact pooling might have overall on testing sensitivity across positive patient detection in the pandemic. abstract: Accommodating large increases in sample workloads has presented one of the biggest challenges to clinical laboratories during the COVID-19 pandemic. Despite the implementation of new automated detection systems, and previous efficiencies such as barcoding, electronic data transfer and extensive robotics, throughput capacities have struggled to meet the demand. Sample pooling has been suggested as an additional strategy to further address this need. The greatest concern with this approach in a clinical setting is the potential for reduced sensitivity, particularly the risk of false negative results when weak positive samples are pooled. To investigate this possibility, detection rates in pooled samples were evaluated, with extensive assessment of pools containing weak positive specimens. Additionally, the frequency of occurrence of weak positive samples across ten weeks of the pandemic were reviewed. Weak positive specimens were detected in all five-sample pools but failed to be detected in four of the 24 nine-sample pools tested. Weak positive samples comprised an average 16.5% of the positive specimens tested during the pandemic thus far, slightly increasing in frequency during later weeks. Other aspects of the testing process should be considered, however, such as accessioning and reporting, which are not streamlined and may be complicated by pooling procedures. Therefore, the impact on the entire laboratory process needs to be carefully assessed prior to implementing such a strategy. url: https://doi.org/10.1101/2020.05.26.118133 doi: 10.1101/2020.05.26.118133 id: cord-294120-8fxrqorg author: Guebre-Xabier, Mimi title: NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge date: 2020-08-19 words: 866.0 sentences: 78.0 pages: flesch: 64.0 cache: ./cache/cord-294120-8fxrqorg.txt txt: ./txt/cord-294120-8fxrqorg.txt summary: title: NVX-CoV2373 vaccine protects cynomolgus macaque upper and lower airways against SARS-CoV-2 challenge Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. And, hACE2 receptor 158 inhibition titers of 649, 1,410, and 1,320 in 2.5, 5, and 25 µg NVX-CoV2373 dose groups 159 respectively were 5.2 -11.2-fold higher than in convalescent sera ( Figure 1C) . Finally, 160 SARS-CoV-2 GMT neutralization antibody titers of 17,920 -23,040 CPE 100 in 161 immunized macaques, were 7.9 -10.1-fold higher than in convalescent sera ( Figure 162 1D) . To evaluate the potential efficacy of NVX-CoV2373 vaccine, macaques were 165 challenged with SARS-CoV-2 virus in upper and lower airways. SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 214 elicits immunogenicity in baboons and protection in mice These interests do not alter the authors adherence to policies on 209 sharing data and materials. abstract: There is an urgent need for a safe and protective vaccine to control the global spread of SARS-CoV-2 and prevent COVID-19. Here, we report the immunogenicity and protective efficacy of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length SARS-CoV-2 spike (S) glycoprotein stabilized in the prefusion conformation. Cynomolgus macaques (Macaca fascicularis) immunized with NVX-CoV2373 and the saponin-based Matrix-M adjuvant induced anti-S antibody that was neutralizing and blocked binding to the human angiotensin-converting enzyme 2 (hACE2) receptor. Following intranasal and intratracheal challenge with SARS-CoV-2, immunized macaques were protected against upper and lower infection and pulmonary disease. These results support ongoing phase 1/2 clinical studies of the safety and immunogenicity of NVX-CoV2327 vaccine (NCT04368988). Highlights Full-length SARS-CoV-2 prefusion spike with Matrix-M1™ (NVX-CoV2373) vaccine. Induced hACE2 receptor blocking and neutralizing antibodies in macaques. Vaccine protected against SARS-CoV-2 replication in the nose and lungs. Absence of pulmonary pathology in NVX-CoV2373 vaccinated macaques. url: https://doi.org/10.1101/2020.08.18.256578 doi: 10.1101/2020.08.18.256578 id: cord-264204-4ablrwuo author: Guintivano, Jerry title: Psychiatric Genomics Research During the COVID-19 Pandemic: A Survey of Psychiatric Genomics Consortium Researchers date: 2020-10-08 words: 3998.0 sentences: 159.0 pages: flesch: 43.0 cache: ./cache/cord-264204-4ablrwuo.txt txt: ./txt/cord-264204-4ablrwuo.txt summary: We provide recommendations for institutions, organizations such as the PGC, as well as individual senior investigators to ensure that the futures of early career investigators, especially those underrepresented in academic medicine such as women and underrepresented minorities, are not disproportionately disadvantaged by the COVID-19 pandemic. Four main themes characterized the comments: maintain team dynamics (e.g., utilizing videoconferencing for regular team meetings, being flexible with deadlines, use clear communication) (32.8% of responses); maintain good personal habits (e.g., keeping in mind productivity may be reduced, practicing self-care, keeping work and personal areas separate) (27.2%); reprioritize research goals (e.g., spending more effort on dry-lab projects rather than wet-lab, using available time to complete analyses or manuscripts, utilizing existing data for new projects) (20.8%); and shift recruitment to online approaches (e.g., phone interviews rather than face-to-face, development of online recruitment and consent protocols) (8.0%). abstract: Between April 20, 2020 and June 19, 2020 we conducted a survey of the membership of the Psychiatric Genomics Consortium (PGC) to explore the impact of COVID-19 on their research and academic careers. A total of 123 individuals responded representing academic ranks from trainee to full professor, tenured and fixed-term appointments, and all genders. The survey included both quantitative and free text responses. Results revealed considerable concern about the impact of COVID-19 on research with the greatest concern reported by individuals in non-permanent positions and female researchers. Concerns about the availability of funding and the impact of the pandemic on career progression were commonly reported by early career researchers. We provide recommendations for institutions, organizations such as the PGC, as well as individual senior investigators to ensure that the futures of early career investigators, especially those underrepresented in academic medicine such as women and underrepresented minorities, are not disproportionately disadvantaged by the COVID-19 pandemic. url: https://www.ncbi.nlm.nih.gov/pubmed/33052336/ doi: 10.1101/2020.10.08.331421 id: cord-280392-ij5gtesw author: Gultom, Mitra title: Susceptibility of well-differentiated airway epithelial cell cultures from domestic and wildlife animals to SARS-CoV-2 date: 2020-11-10 words: 2253.0 sentences: 140.0 pages: flesch: 50.0 cache: ./cache/cord-280392-ij5gtesw.txt txt: ./txt/cord-280392-ij5gtesw.txt summary: In this study, we inoculated well-differentiated animal AEC cultures of monkey, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two neotropical bat species with SARS-CoV-2. The AEC 131 cultures from 12 different species (rhesus macaque, cat, ferret, dog, rabbit, pig, cattle, goat, llama, 132 camel, and two neotropical bats) were inoculated with 10.000 TCID50 of either IAV or IDV and incubated 133 at 33°C and 37°C. For IDV we observed 137 antigen-positive cells in all AEC model, except for rhesus macaque and one of the neotropical bat 138 species, indicating that the AEC cultures were all well-differentiated and susceptible to virus infection. In the viral sequences in the 96 hpi samples from virus-infected 156 rhesus macaque and cat AEC cultures, we observed no obvious signs of nucleotide transitions that lead 157 to nonsynonymous mutations compared to the respective inoculums ( Fig. 3) , irrespective of 158 temperature and animal species. abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread globally, and the number of cases continues to rise all over the world. Besides humans, the zoonotic origin, as well as intermediate and potential spillback host reservoirs of SARS-CoV-2 are unknown. To circumvent ethical and experimental constraints, and more importantly, to reduce and refine animal experimentation, we employed our airway epithelial cell (AEC) culture repository composed of various domesticated and wildlife animal species to assess their susceptibility to SARS-CoV-2. In this study, we inoculated well-differentiated animal AEC cultures of monkey, cat, ferret, dog, rabbit, pig, cattle, goat, llama, camel, and two neotropical bat species with SARS-CoV-2. We observed that SARS-CoV-2 only replicated efficiently in monkey and cat AEC culture models. Whole-genome sequencing of progeny virus revealed no obvious signs of nucleotide transitions required for SARS-CoV-2 to productively infect monkey and cat epithelial airway cells. Our findings, together with the previously reported human-to-animal spillover events warrants close surveillance to understand the potential role of cats, monkeys, and closely related species as spillback reservoirs for SARS-CoV-2. url: https://doi.org/10.1101/2020.11.10.374587 doi: 10.1101/2020.11.10.374587 id: cord-270698-9w3ap3gz author: Guo, Hua title: Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes date: 2020-05-13 words: 2496.0 sentences: 142.0 pages: flesch: 59.0 cache: ./cache/cord-270698-9w3ap3gz.txt txt: ./txt/cord-270698-9w3ap3gz.txt summary: title: Evolutionary arms race between virus and host drives genetic diversity in bat SARS related coronavirus spike genes The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. Consistent results were observed by binding affinity assays between SARSand SARSr-CoV spike proteins and receptor molecules from bats and humans. In a host-virus arms race situation, the genes involved tend to display dN/dS ratios Codon-based analysis of molecular evolution 536 Bat ACE2 and SARSr-CoV spike sequences were analyzed for positive selection. Identification of key amino acid 671 residues required for horseshoe bat angiotensin-I converting enzyme 2 to function as a 672 receptor for severe acute respiratory syndrome coronavirus abstract: The Chinese horseshoe bat (Rhinolophus sinicus), reservoir host of severe acute respiratory syndrome coronavirus (SARS-CoV), carries many bat SARS-related CoVs (SARSr-CoVs) with high genetic diversity, particularly in the spike gene. Despite these variations, some bat SARSr-CoVs can utilize the orthologs of human SARS-CoV receptor, angiotensin-converting enzyme 2 (ACE2), for entry. It is speculated that the interaction between bat ACE2 and SARSr-CoV spike proteins drives diversity. Here, we have identified a series of R. sinicus ACE2 variants with some polymorphic sites involved in the interaction with the SARS-CoV spike protein. Pseudoviruses or SARSr-CoVs carrying different spike proteins showed different infection efficiency in cells transiently expressing bat ACE2 variants. Consistent results were observed by binding affinity assays between SARS- and SARSr-CoV spike proteins and receptor molecules from bats and humans. All tested bat SARSr-CoV spike proteins had a higher binding affinity to human ACE2 than to bat ACE2, although they showed a 10-fold lower binding affinity to human ACE2 compared with their SARS-CoV counterpart. Structure modeling revealed that the difference in binding affinity between spike and ACE2 might be caused by the alteration of some key residues in the interface of these two molecules. Molecular evolution analysis indicates that these residues were under strong positive selection. These results suggest that the SARSr-CoV spike protein and R. sinicus ACE2 may have coevolved over time and experienced selection pressure from each other, triggering the evolutionary arms race dynamics. It further proves that R. sinicus is the natural host of SARSr-CoVs. Importance Evolutionary arms race dynamics shape the diversity of viruses and their receptors. Identification of key residues which are involved in interspecies transmission is important to predict potential pathogen spillover from wildlife to humans. Previously, we have identified genetically diverse SARSr-CoV in Chinese horseshoe bats. Here, we show the highly polymorphic ACE2 in Chinese horseshoe bat populations. These ACE2 variants support SARS- and SARSr-CoV infection but with different binding affinity to different spike proteins. The higher binding affinity of SARSr-CoV spike to human ACE2 suggests that these viruses have the capacity of spillover to humans. The positive selection of residues at the interface between ACE2 and SARSr-CoV spike protein suggests a long-term and ongoing coevolutionary dynamics between them. Continued surveillance of this group of viruses in bats is necessary for the prevention of the next SARS-like disease. url: https://doi.org/10.1101/2020.05.13.093658 doi: 10.1101/2020.05.13.093658 id: cord-320165-1b6sycgv author: Guo, Qirui title: Small molecules inhibit SARS-COV-2 induced aberrant inflammation and viral replication in mice by targeting S100A8/A9-TLR4 axis date: 2020-09-09 words: 6762.0 sentences: 425.0 pages: flesch: 54.0 cache: ./cache/cord-320165-1b6sycgv.txt txt: ./txt/cord-320165-1b6sycgv.txt summary: S100A8/A9 specific inhibitor, Paquinimod, significantly reduced the number of neutrophils activated by the coronavirus, inhibited viral replication and rescued lung damage a result of SARS-CoV-2 infection. The whole genome wide RNA-seq analysis of the lungs from infected rhesus macaques showed that a number of transcripts were induced or inhibited at day 3 and day 5 after SARS-CoV-2 infection (Supplementary Figure 1A) . Similar to the data from rhesus macaque experiments, compared to other alarmins, S100A8 was robustly induced by SARS-CoV-2 but not by IAV infection in mice ( Figure 2E ). The expression of these B cell related genes was rescued or induced by Paquinimod during MHV infection, which was confirmed by qRT-PCR analysis ( Figure 3M ). Moreover, both Paquinimod and Resatorvid suppressed the activation of coronavirus related neutrophils in lung during SARS-CoV-2 infection ( Figure 4D ). abstract: The SARS-CoV-2 pandemic poses an unprecedented public health crisis. Accumulating evidences suggest that SARS-CoV-2 infection causes dysregulation of immune system. However, the unique signature of early immune responses remains elusive. We characterized the transcriptome of rhesus macaques and mice infected with SARS-CoV-2. Alarmin S100A8 was robustly induced by SARS-CoV-2 in animal models as well as in COVID-19 patients. Paquinimod, a specific inhibitor of S100A8/A9, could reduce inflammatory response and rescue the pneumonia with substantial reduction of viral titers in SASR-CoV-2 infected animals. Remarkably, Paquinimod treatment resulted in 100% survival of mice in a lethal model of mouse coronavirus (MHV) infection. A novel group of neutrophils that contributed to the uncontrolled inflammation and onset of COVID-19 were dramatically induced by coronavirus infections. Paquinimod treatment could reduce these neutrophils and regain antiviral responses, unveiling key roles of S100A8/A9 and noncanonical neutrophils in the pathogenesis of COVID-19, highlighting new opportunities for therapeutic intervention. url: https://doi.org/10.1101/2020.09.09.288704 doi: 10.1101/2020.09.09.288704 id: cord-298172-iyxyennq author: Guo, Youjia title: Potent mouse monoclonal antibodies that block SARS-CoV-2 infection date: 2020-10-02 words: 4557.0 sentences: 295.0 pages: flesch: 49.0 cache: ./cache/cord-298172-iyxyennq.txt txt: ./txt/cord-298172-iyxyennq.txt summary: Various recombinant monoclonal antibodies of human origin that neutralize SARS-CoV-2 infection have been isolated from convalescent patients and will be applied as therapies and prophylaxis. Here, we produced mouse anti-SARS-CoV-2 spike monoclonal antibodies that exhibit not only robust performance in immunoassays including western blotting, ELISA, immunofluorescence, and immunoprecipitation, but also neutralizing activity against SARS-CoV-2 infection in vitro. Among them, two antibodies were shown to attenuate the interaction of spike proteins with ACE2 and neutralized infection of VeroE6/TMPRSS2 cells by SARS-CoV-2. Mice were immunized with these recombinant spike proteins to generate antibodies against the SARS-CoV-2 virus, followed by cell fusion to generate a hybridoma-producing antibody. The performance of our antibodies in IP experiments prompted us to examine whether they were capable of inhibiting spike-ACE2 binding or even neutralizing SARS-CoV-2 infection. Our antibodies, S1D7 and S3D8, have been shown to attenuate the interaction of spike proteins with ACE2 and neutralize infection of VeroE6/TM2 cells by SARS-CoV-2. abstract: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has developed into a global pandemic since its first outbreak in the winter of 2019. An extensive investigation of SARS-CoV-2 is critical for disease control. Various recombinant monoclonal antibodies of human origin that neutralize SARS-CoV-2 infection have been isolated from convalescent patients and will be applied as therapies and prophylaxis. However, the need for dedicated monoclonal antibodies in molecular pathology research is not fully addressed. Here, we produced mouse anti-SARS-CoV-2 spike monoclonal antibodies that exhibit not only robust performance in immunoassays including western blotting, ELISA, immunofluorescence, and immunoprecipitation, but also neutralizing activity against SARS-CoV-2 infection in vitro. Our monoclonal antibodies are of mouse origin, making them compatible with the experimental immunoassay setups commonly used in basic molecular biology research laboratories, and large-scale production and easy distribution are guaranteed by conventional mouse hybridoma technology. url: https://doi.org/10.1101/2020.10.01.323220 doi: 10.1101/2020.10.01.323220 id: cord-102705-mcit0luk author: Gupta, Chitrak title: Mind reading of the proteins: Deep-learning to forecast molecular dynamics date: 2020-07-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Molecular dynamics (MD) simulations have emerged to become the back-bone of today’s computational biophysics. Simulation tools such as, NAMD, AMBER and GROMACS have accumulated more than 100,000 users. Despite this remarkable success, now also bolstered by compatibility with graphics processor units (GPUs) and exascale computers, even the most scalable simulations cannot access biologically relevant timescales - the number of numerical integration steps necessary for solving differential equations in a million-to-billion-dimensional space is computationally in-tractable. Recent advancements in Deep Learning has made it such that patterns can be found in high dimensional data. In addition, Deep Learning have also been used for simulating physical dynamics. Here, we utilize LSTMs in order to predict future molecular dynamics from current and previous timesteps, and examine how this physics-guided learning can benefit researchers in computational biophysics. In particular, we test fully connected Feed-forward Neural Networks, Recurrent Neural Networks with LSTM / GRU memory cells with TensorFlow and PyTorch frame-works trained on data from NAMD simulations to predict conformational transitions on two different biological systems. We find that non-equilibrium MD is easier to train and performance improves under the assumption that each atom is independent of all other atoms in the system. Our study represents a case study for high-dimensional data that switches stochastically between fast and slow regimes. Applications of resolving these sets will allow real-world applications in the interpretation of data from Atomic Force Microscopy experiments. url: https://doi.org/10.1101/2020.07.28.225490 doi: 10.1101/2020.07.28.225490 id: cord-300078-svu06v9c author: Haghani, Milad title: Covid-19 pandemic and the unprecedented mobilisation of scholarly efforts prompted by a health crisis: Scientometric comparisons across SARS, MERS and 2019-nCov literature date: 2020-06-01 words: 6365.0 sentences: 298.0 pages: flesch: 52.0 cache: ./cache/cord-300078-svu06v9c.txt txt: ./txt/cord-300078-svu06v9c.txt summary: To compare the scientometric aspects of the studies on SARS, MERS and Covid-19, three separate datasets of publications on these three topics were retrieved from Scopus through three separate search strategies. Figures A1 and A2 in the Appendix illustrate the map associated with the SARS literature overlaid respectively with the average year of publication and average number of citations associated with the studies where these keywords have occurred. Maps of term occurrences based on the analysis of the title and abstract of studies on SARS, MERS and Covid-19 have also been presented in Figures 7, 8 and 9 respectively. An inspection of the maps overlaid with the average year of publications for SARS and MERS in Figures A1 and A3 in the Appendix suggests that, on average, this cohort of studies are generally the last to emerge in the published domain compared to the two other major clusters, but they receive relatively high citations on average (according to Figures A2, A4 and A6). abstract: During the current century, each major coronavirus outbreak has triggered a quick and immediate surge of academic publications on this topic. The spike in research publications following the 2019 Novel Coronavirus (Covid-19) outbreak, however, has been like no other. The global crisis caused by the Covid-19 pandemic has mobilised scientific efforts in an unprecedented way. In less than five months, more than 12,000 research items have been indexed while the number increasing every day. With the crisis affecting all aspects of life, research on Covid-19 seems to have become a focal point of interest across many academic disciplines. Here, scientometric aspects of the Covid-19 literature are analysed and contrasted with those of the two previous major Coronavirus diseases, i.e. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The focus is on the co-occurrence of key-terms, bibliographic coupling and citation relations of journals and collaborations between countries. Certain recurring patterns across all three literatures were discovered. All three outbreaks have commonly generated three distinct and major cohort of studies: (i) studies linked to the public health response and epidemic control, (ii) studies associated with the chemical constitution of the virus and (iii) studies related to treatment, vaccine and clinical care. While studies affiliated with the category (i) seem to have been the first to emerge, they overall received least numbers of citations compared to those of the two other categories. Covid-19 studies seem to have been distributed across a broader variety of journals and subject areas. Clear links are observed between the geographical origins of each outbreak or the local geographical severity of each outbreak and the magnitude of research originated from regions. Covid-19 studies also display the involvement of authors from a broader variety of countries compared to SARS and MRS. url: https://doi.org/10.1101/2020.05.31.126813 doi: 10.1101/2020.05.31.126813 id: cord-102958-q8jamg07 author: Hahka, Taija M. title: Resiniferatoxin (RTX) ameliorates acute respiratory distress syndrome (ARDS) in a rodent model of lung injury date: 2020-09-14 words: 3737.0 sentences: 219.0 pages: flesch: 45.0 cache: ./cache/cord-102958-q8jamg07.txt txt: ./txt/cord-102958-q8jamg07.txt summary: We ablated cardiopulmonary spinal afferents through either epidural T1-T4 dorsal root ganglia (DRG) application or intra-stellate ganglia delivery of a selective afferent neurotoxin, resiniferatoxin (RTX) in rats 3 days post bleomycin-induced lung injury. Our data showed that both epidural and intra-stellate ganglia injection of RTX significantly reduced plasma extravasation and reduced the level of lung pro-inflammatory cytokines providing proof of principle that cardiopulmonary spinal afferents are involved in lung pathology post ALI. Therefore, in the current study we hypothesized that ablation of lung afferent innervation (thoracic spinal) by application of an ultrapotent, selective afferent neurotoxin, resiniferatoxin (RTX) will modify the course of the pathology including lung edema and local pulmonary inflammation associated with progressive ALI. 2 1 Our data suggest that pulmonary spinal afferent ablation by intra-stellate injection of RTX reduces plasma extravasation and local pulmonary inflammation post bleomycininduced lung injury which results in improved blood gas exchange. abstract: Acute lung injury (ALI) is associated with cytokine release, pulmonary edema and in the longer term, fibrosis. A severe cytokine storm and pulmonary pathology can cause respiratory failure due to acute respiratory distress syndrome (ARDS), which is one of the major causes of mortality associated with ALI. In this study, we aimed to determine a novel neural component through cardiopulmonary spinal afferents that mediates lung pathology during ALI/ARDS. We ablated cardiopulmonary spinal afferents through either epidural T1-T4 dorsal root ganglia (DRG) application or intra-stellate ganglia delivery of a selective afferent neurotoxin, resiniferatoxin (RTX) in rats 3 days post bleomycin-induced lung injury. Our data showed that both epidural and intra-stellate ganglia injection of RTX significantly reduced plasma extravasation and reduced the level of lung pro-inflammatory cytokines providing proof of principle that cardiopulmonary spinal afferents are involved in lung pathology post ALI. Considering the translational potential of stellate ganglia delivery of RTX, we further examined the effects of stellate RTX on blood gas exchange and lung edema in the ALI rat model. Our data suggest that intra-stellate ganglia injection of RTX improved pO2 and blood acidosis 7 days post ALI. It also reduced wet lung weight in bleomycin treated rats, indicating a reduction in lung edema. Taken together, this study suggests that cardiopulmonary spinal afferents play a critical role in lung inflammation and edema post ALI. This study shows the translational potential for ganglionic administration of RTX in ARDS. url: https://doi.org/10.1101/2020.09.14.296731 doi: 10.1101/2020.09.14.296731 id: cord-255895-6at9gelt author: Han, Namshik title: Identification of SARS-CoV-2 induced pathways reveal drug repurposing strategies date: 2020-08-25 words: 4736.0 sentences: 269.0 pages: flesch: 52.0 cache: ./cache/cord-255895-6at9gelt.txt txt: ./txt/cord-255895-6at9gelt.txt summary: We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by COVID-19 multi-omic datasets(Bojkova et al., 2020; Gordon et al., 2020), and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials(Clinicaltrials.gov, 2020) testifying to the validity of the approach. Importantly, treatment of Calu-3 and Vero E6 cell lines with Proguanil and Sulfasalazine led to a significant downregulation of the mRNA of key cytokines (Figures 4G-J and S8), which are dictated by the p38/MAPK signalling pathway and shown to become elevated during SARS-CoV-2 infection and replication (CXCL3, IFNB1 and TNF-A). Here we have used a series of computational approaches, including bespoke methods for data integration, network analysis, computer simulation and machine learning, to identify novel SARS-CoV-2 induced pathways that could be targeted therapeutically by repurposing existing and approved drugs ( Figure S9 ). abstract: The global outbreak of SARS-CoV-2 necessitates the rapid development of new therapies against COVID-19 infection. Here, we present the identification of 200 approved drugs, appropriate for repurposing against COVID-19. We constructed a SARS-CoV-2-induced protein (SIP) network, based on disease signatures defined by COVID-19 multi-omic datasets(Bojkova et al., 2020; Gordon et al., 2020), and cross-examined these pathways against approved drugs. This analysis identified 200 drugs predicted to target SARS-CoV-2-induced pathways, 40 of which are already in COVID-19 clinical trials(Clinicaltrials.gov, 2020) testifying to the validity of the approach. Using artificial neural network analysis we classified these 200 drugs into 9 distinct pathways, within two overarching mechanisms of action (MoAs): viral replication (130) and immune response (70). A subset of drugs implicated in viral replication were tested in cellular assays and two (proguanil and sulfasalazine) were shown to inhibit replication. This unbiased and validated analysis opens new avenues for the rapid repurposing of approved drugs into clinical trials. url: https://doi.org/10.1101/2020.08.24.265496 doi: 10.1101/2020.08.24.265496 id: cord-103524-1w9tdhdd author: Hao, Siyuan title: Establishment of a Replicon System for Bourbon Virus and Identification of Small Molecules that Efficiently Inhibit Virus Replication date: 2020-04-25 words: 4241.0 sentences: 237.0 pages: flesch: 61.0 cache: ./cache/cord-103524-1w9tdhdd.txt txt: ./txt/cord-103524-1w9tdhdd.txt summary: By using the luciferase reporter, we screened a few small molecule compounds of anti-endonuclease that inhibited the nicking activity by parvovirus B19 (B19V) NS1, as well as FDA-approved drugs targeting the RdRP of influenza virus. Our results demonstrated that myricetin, and an anti-B19V NS1 nicking inhibitor, efficiently inhibited the RdRP activity of BRBV and virus replication. We then used the replicon reporter to examine anti-influenza drugs that target viral RNA-dependent RNA polymerase (RdRP) and endonuclease inhibitors of human parvovirus B19 (B19V) for inhibition of BRBV RdRP activity and BRBV replication in HEK293T and Vero cells. BRBV GFP reporter assay: pHW-ΔCMV-GP-GFP was co-transfected with the four pcDNA-PA, PB1, PB2, and NP plasmids into HEK293T cells confluent in six-well plates. BRBV luciferase reporter assay: pHW-ΔCMV-GP-gLuc and the four pcDNA-based plasmids were co-transfected into HEK293T cells in 96-well plate. abstract: Bourbon virus (BRBV) was first isolated from a patient hospitalized at the University of Kansas Hospital in 2014. Since then, several deaths have been reported to be caused by BRBV infection in the Midwest and Southern United States. BRBV is a tick-borne virus that is widely carried by lone star ticks. It belongs to genus Thogotovirus of the Orthomyxoviridae family. Currently, there are no treatments or vaccines available for BRBV or thogotovirus infection caused diseases. In this study, we reconstituted a replicon reporter system, composed of plasmids expressing the RNA-dependent RNA polymerase (RdRP) complex (PA, PB1 and PB2), nucleocapsid (NP) protein, and a reporter gene flanked by the 3’ and 5’ UTR of the envelope glycoprotein (GP) genome segment. By using the luciferase reporter, we screened a few small molecule compounds of anti-endonuclease that inhibited the nicking activity by parvovirus B19 (B19V) NS1, as well as FDA-approved drugs targeting the RdRP of influenza virus. Our results demonstrated that myricetin, and an anti-B19V NS1 nicking inhibitor, efficiently inhibited the RdRP activity of BRBV and virus replication. The IC50 and EC50 of myricetin are 2.22 μM and 4.6 μM, respectively, in cells. Myricetin had minimal cytotoxicity in cells, and therefore the therapeutic index of the compound is high. In conclusion, the BRBV replicon system is a useful tool to study viral RNA replication and to develop antivirals, and myricetin may hold promise in treatment of BRBV infected patients. url: https://doi.org/10.1101/2020.04.24.058693 doi: 10.1101/2020.04.24.058693 id: cord-337973-djqzgc1k author: Hao, Siyuan title: Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium date: 2020-08-28 words: 2624.0 sentences: 166.0 pages: flesch: 54.0 cache: ./cache/cord-337973-djqzgc1k.txt txt: ./txt/cord-337973-djqzgc1k.txt summary: title: Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium We also identified that SARS-CoV-2 does not infect HAE from the basolateral side, and the dominant SARS-CoV-2 permissive epithelial cells are ciliated cells and goblet cells, whereas virus replication in basal cells and club cells was not detectable. Our observation that SARS-CoV-2 was unable to infect epithelial cells from the 299 basolateral side supports that the viral entry receptor ACE2 is polarly expressed at the apical 300 side 30, 31 . We 332 determined that 1 pfu of SARS-CoV-2 in Vero-E6 cells has a particle (viral genome copy) 333 number of 820, suggesting that a load of 2.46 x 10 5 particles is required to productively infect 1 334 cm 2 of the airway epithelium, which is much higher than the small DNA virus parvovirus human 335 bocavirus 1 (HBoV1) we studied 55 . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) replicates throughout human airways. The polarized human airway epithelium (HAE) cultured at an airway-liquid interface (HAE-ALI) is an in vitro model mimicking the in vivo human mucociliary airway epithelium and supports the replication of SARS-CoV-2. However, previous studies only characterized short-period SARS-CoV-2 infection in HAE. In this study, continuously monitoring the SARS-CoV-2 infection in HAE-ALI cultures for a long period of up to 51 days revealed that SARS-CoV-2 infection was long lasting with recurrent replication peaks appearing between an interval of approximately 7-10 days, which was consistent in all the tested HAE-ALI cultures derived from 4 lung bronchi of independent donors. We also identified that SARS-CoV-2 does not infect HAE from the basolateral side, and the dominant SARS-CoV-2 permissive epithelial cells are ciliated cells and goblet cells, whereas virus replication in basal cells and club cells was not detectable. Notably, virus infection immediately damaged the HAE, which is demonstrated by dispersed Zonula occludens-1 (ZO-1) expression without clear tight junctions and partial loss of cilia. Importantly, we identified that SARS-CoV-2 productive infection of HAE requires a high viral load of 2.5 × 105 virions per cm2 of epithelium. Thus, our studies highlight the importance of a high viral load and that epithelial renewal initiates and maintains a recurrent infection of HAE with SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32869024/ doi: 10.1101/2020.08.27.271130 id: cord-307811-6e3j0pn7 author: Hao, Wei title: Binding of the SARS-CoV-2 Spike Protein to Glycans date: 2020-07-02 words: 5665.0 sentences: 299.0 pages: flesch: 54.0 cache: ./cache/cord-307811-6e3j0pn7.txt txt: ./txt/cord-307811-6e3j0pn7.txt summary: Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. Previous studies of many other viruses suggested that SARS-CoV-2 S protein may use other molecules on host cell surface as attachment factors to facilitate binding to the high-affinity receptor ACE2. 36 A recent study suggested that HS may bind to the receptor binding domain (RBD, the C-terminal region of the S1 subunit, Fig. 2 ) of the SARS-CoV-2 spike protein and change its conformation. 38 In this study, we systematically examined and compared the binding of the SARS-CoV-2 S protein subunits, full-length molecule and its trimer to different HS using microarray experiments (Fig. 2) . In addition to binding protein-based receptors, many viruses can interact with cell surface glycans, including GAGs and sialic acid-containing oligosaccharides. abstract: The pandemic of SARS-CoV-2 has caused a high number of deaths in the world. To combat it, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. In this study, we examined and compared the binding of the subunits and spike (S) proteins of SARS-CoV-2 and SARS-CoV, MERS-CoV to these glycans. Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner, the length of HS is not a critical factor for the binding, and no binding with sialic acid residues was detected. Overall, this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells, and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses. url: https://doi.org/10.1101/2020.05.17.100537 doi: 10.1101/2020.05.17.100537 id: cord-102156-v98vrely author: Harda, Zofia title: Loss of mu and delta opioid receptors on neurons expressing dopamine receptor D1 has no effect on reward sensitivity date: 2020-03-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Opioid signaling controls the activity of the brain’s reward system. It is involved in signaling the hedonic effects of rewards and also has essential roles in reinforcement and motivational processes. Here, we focused on opioid signaling through mu and delta receptors on dopaminoceptive neurons and evaluated the role these receptors play in reward-driven behaviors. We generated a genetically modified mouse with selective double knockdown of mu and delta opioid receptors in neurons expressing dopamine receptor D1. Selective expression of the transgene was confirmed using immunostaining. Knockdown was validated by measuring the effects of selective opioid receptor agonists on neuronal membrane currents using whole-cell patch clamp recordings. We found that in the nucleus accumbens of control mice, the majority of dopamine receptor D1-expressing neurons were sensitive to a mu or delta opioid agonist. In mutant mice, the response to the delta receptor agonist was blocked, while the effects of the mu agonist were strongly attenuated. Behaviorally, the mice had no obvious impairments. The mutation did not affect sensitivity to the rewarding effects of morphine injections or social contact and had no effect on preference for sweet taste. Knockdown had a moderate effect on motor activity in some of the tests performed, but this effect did not reach statistical significance. Thus, we found that knocking down mu and delta receptors on dopamine receptor D1-expressing cells does not appreciably affect reward-driven behaviors. Highlights – It is well accepted that opioid signaling controls the brain’s reward system – We generated mutant mice with mu and delta receptor knockdown in D1 neurons – Knockdown made dopaminoceptive neurons insensitive to mu and delta opioid receptor agonists – The mutation did not cause obvious behavioral impairments – The loss of mu and delta receptors on D1 neurons does not affect reward sensitivity url: https://doi.org/10.1101/2020.03.18.996454 doi: 10.1101/2020.03.18.996454 id: cord-336012-8klkojpo author: Harilal, Divinlal title: SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission date: 2020-06-18 words: 3040.0 sentences: 144.0 pages: flesch: 45.0 cache: ./cache/cord-336012-8klkojpo.txt txt: ./txt/cord-336012-8klkojpo.txt summary: Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic. Here we show that cWGS is cost-effective and is highly scalable when using a target enrichment sequencing method, and we also demonstrate its utility in tracking the origin of SARS-CoV-2 transmission. abstract: Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic. url: https://doi.org/10.1101/2020.06.06.138339 doi: 10.1101/2020.06.06.138339 id: cord-103868-iwpiti2h author: Harrison, Angela R. title: The Ebola virus interferon antagonist VP24 undergoes active nucleocytoplasmic trafficking date: 2020-08-11 words: 2255.0 sentences: 124.0 pages: flesch: 45.0 cache: ./cache/cord-103868-iwpiti2h.txt txt: ./txt/cord-103868-iwpiti2h.txt summary: Functions of the Ebola virus (EBOV) IFN antagonist VP24 include nucleocapsid assembly during cytoplasmic replication and inhibition of IFN-activated signalling by STAT1. Proteins of many viruses with cytoplasmic replication cycles similar to EBOV interact with the nuclear trafficking machinery, resulting in active nucleocytoplasmic shuttling important to immune evasion and other intranuclear functions. Thus, it appears that active In this study we have shown that EBOV VP24 undergoes active trafficking between the nucleus 275 and cytoplasm involving CRM1-dependent nuclear export via a NES at the VP24 C-terminus. Notably, the EBOV 287 matrix protein VP40 has also been reported to localise to the nucleus in infected and transfected 288 cells (16, 50); however, a direct role for active trafficking pathways to regulate localisation, 289 distinct from mechanisms such as diffusion or interaction with other host factors, has not been 290 defined. abstract: Viral interferon (IFN) antagonist proteins mediate evasion of IFN-mediated innate immunity and are often multifunctional, having distinct roles in viral replication processes. Functions of the Ebola virus (EBOV) IFN antagonist VP24 include nucleocapsid assembly during cytoplasmic replication and inhibition of IFN-activated signalling by STAT1. For the latter, VP24 prevents STAT1 nuclear import via competitive binding to nuclear import receptors (karyopherins). Many viral proteins, including proteins from viruses with cytoplasmic replication cycles, interact with the trafficking machinery to undergo nucleocytoplasmic transport, with key roles in pathogenesis. Despite established karyopherin interaction, the nuclear trafficking profile of VP24 has not been investigated. We find that VP24 becomes strongly nuclear following overexpression of karyopherin or inhibition of nuclear export pathways. Molecular mapping indicates that cytoplasmic localisation of VP24 depends on a CRM1-dependent nuclear export sequence at the VP24 C-terminus. Nuclear export is not required for STAT1 antagonism, consistent with competitive karyopherin binding being the principal antagonistic mechanism while export mediates return of nuclear VP24 to the cytoplasm for replication functions. Thus, nuclear export of VP24 might provide novel targets for antiviral approaches. Importance Ebola virus (EBOV) is the causative agent of ongoing outbreaks of severe haemorrhagic fever with case-fatality rates between 40 and 60%. Proteins of many viruses with cytoplasmic replication cycles similar to EBOV interact with the nuclear trafficking machinery, resulting in active nucleocytoplasmic shuttling important to immune evasion and other intranuclear functions. However, exploitation of host trafficking machinery for nucleocytoplasmic transport by EBOV has not been directly examined. We find that the EBOV protein VP24 is actively trafficked between the nucleus and cytoplasm, and identify the specific pathways and sequences involved. The data indicate that nucleocytoplasmic trafficking is important for the multifunctional nature of VP24, which has critical roles in immune evasion and viral replication, identifying a new mechanism in infection by this highly lethal pathogen, and potential target for antivirals. url: https://doi.org/10.1101/2020.08.10.245563 doi: 10.1101/2020.08.10.245563 id: cord-297786-jz1d1m2e author: Hasan, Md. Mahbub title: Global and Local Mutations in Bangladeshi SARS-CoV-2 Genomes date: 2020-08-26 words: 3271.0 sentences: 187.0 pages: flesch: 54.0 cache: ./cache/cord-297786-jz1d1m2e.txt txt: ./txt/cord-297786-jz1d1m2e.txt summary: Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Then, we studied the variants present in different isolates of Bangladesh to investigate the pattern of mutations, identify UMs, and discuss the pseudo-effect of these mutations on the structure and function of encoded proteins, with their role in pathogenicity. To understand the SARS-CoV-2 viral transmission in Bangladesh, we performed phylogenetic analysis on the selected 207 viral genomes reported from different districts of Bangladesh along with selected 467 globally submitted sequences as reported from 42 countries and 6 continents ( Figure 1 ). abstract: Corona Virus Disease-2019 (COVID-19) warrants comprehensive investigations of publicly available Severe Acute Respiratory Syndrome-CoronaVirus-2 (SARS-CoV-2) genomes to gain new insight about their epidemiology, mutations and pathogenesis. Nearly 0.4 million mutations were identified so far in ∼60,000 SARS-CoV-2 genomic sequences. In this study, we compared 207 of SARS-CoV-2 genomes reported from different parts of Bangladesh and their comparison with 467 globally reported sequences to understand the origin of viruses, possible patterns of mutations, availability of unique mutations, and their apparent impact on pathogenicity of the virus in victims of Bangladeshi population. Phylogenetic analyses indicates that in Bangladesh, SARS-CoV-2 viruses might arrived through infected travelers from European countries, and the GR clade was found as predominant in this region. We found 2602 mutations including 1602 missense mutations, 612 synonymous mutations, 36 insertions and deletions with 352 other mutations types. In line with the global trend, D614G mutation in spike glycoprotein was predominantly high (95.6%) in Bangladeshi isolates. Interestingly, we found the average number of mutations in ORF1ab, S, ORF3a, M and N of genomes, having nucleotide shift at G614 (n=459), were significantly higher (p≤0.001) than those having mutation at D614 (n=215). Previously reported frequent mutations such as P4715L, D614G, R203K, G204R and I300F were also prevalent in Bangladeshi isolates. Additionally, 87 unique amino acid changes were revealed and were categorized as originating from different cities of Bangladesh. The analyses would increase our understanding of variations in virus genomes circulating in Bangladesh and elsewhere and help develop novel therapeutic targets against SARS-CoV-2. url: https://doi.org/10.1101/2020.08.25.267658 doi: 10.1101/2020.08.25.267658 id: cord-102504-d840uu3e author: Hass, Kenneth N. title: Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) System for Rapid Viral DNA Sensing date: 2020-03-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: A fully Integrated Micropillar Polydimethylsiloxane Accurate CRISPR Detection (IMPACT) system is developed for viral DNA detection. This powerful system is patterned with high-aspect ratio micropillars to enhance reporter probe binding. After surface modification and probe immobilization, CRISPR Cas12a/crRNA complex is injected into the fully enclosed system. With the presence of double-stranded DNA target, the CRISPR enzyme is activated and non-specifically cleaves the ssDNA reporters initially immobilized on the micropillars. This collateral cleavage releases fluorescence dyes into the assay, and the intensity is linearly proportional to the target DNA concentration ranging from 0.1 to 10 nM. Importantly, this system does not rely on traditional dye-quencher labeled probe thus eliminating the fluorescence background presented in the assay. Furthermore, our one-step detection protocol is performed at isothermal conditions (37°C) without using complicated and time-consuming off-chip probe hybridization and denaturation. This miniaturized and fully packed IMPACT chip demonstrates rapid, sensitive, and simple nucleic acid detection and is an ideal candidate for the next generation molecular diagnostic platform for point-of-care (POC) applications, responding to emerging and deadly pathogen outbreaks. url: https://doi.org/10.1101/2020.03.17.994137 doi: 10.1101/2020.03.17.994137 id: cord-312999-3erodkv9 author: Hassan, Sk. Sarif title: Notable sequence homology of the ORF10 protein introspects the architecture of SARS-COV-2 date: 2020-09-06 words: 3920.0 sentences: 236.0 pages: flesch: 53.0 cache: ./cache/cord-312999-3erodkv9.txt txt: ./txt/cord-312999-3erodkv9.txt summary: SARS-CoV-2 has been reported to be uniquely characterized by the accessory protein ORF10, which contains eleven cytotoxic T lymphocyte (CTL) epitopes of nine amino acids length each, across various human leukocyte antigen (HLA) subtypes. In this study, all missense mutations found in sequence databases were examined across twnety-two unique SARS-CoV-2 ORF10 variants that could possibly alter viral pathogenicity. The high degree of physicochemical and structural similarity of ORF10 proteins of SARS-CoV-2 and Pangolin-CoV open questions about the architecture of SARS-CoV-2 due to the disagreement of these two ORF10 proteins over their sub-structure (loop/coil region), solubility, antigenicity and change from the strand to coil at amino acid position 26, where tyrosine is present. Based on the mutations, conserved and non-conserved residues in ORF10 proteins are identified and marked in different colors in (Figure There are altogether 22 distinct missense mutations which were examined across 22 unique ORF10 variants of SARS-CoV-2. abstract: The global public health is endangered due to COVID-19 pandemic, which is caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Despite having similar pathology to MERS and SARS-CoV, the infection fatality rate of SARS-CoV-2 is likely lower than 1%. SARS-CoV-2 has been reported to be uniquely characterized by the accessory protein ORF10, which contains eleven cytotoxic T lymphocyte (CTL) epitopes of nine amino acids length each, across various human leukocyte antigen (HLA) subtypes. In this study, all missense mutations found in sequence databases were examined across twnety-two unique SARS-CoV-2 ORF10 variants that could possibly alter viral pathogenicity. Some of these mutations decrease the stability of ORF10, e.g. I4L and V6I were found in the MoRF region of ORF10 which may also possibly contribute to Intrinsic protein disorder. Furthermore, a physicochemical and structural comparative analysis was carried out on SARS-CoV-2 and Pangolin-CoV ORF10 proteins, which share 97.37% amino acid homology. The high degree of physicochemical and structural similarity of ORF10 proteins of SARS-CoV-2 and Pangolin-CoV open questions about the architecture of SARS-CoV-2 due to the disagreement of these two ORF10 proteins over their sub-structure (loop/coil region), solubility, antigenicity and change from the strand to coil at amino acid position 26, where tyrosine is present. Altogether, SARS-CoV-2 ORF10 is a promising pharmaceutical target and a protein which should be monitored for changes which correlate to change pathogenesis and clinical course of COVID-19 infection. url: https://doi.org/10.1101/2020.09.06.284976 doi: 10.1101/2020.09.06.284976 id: cord-338055-2d6n4cve author: Hassan, Sk. Sarif title: A unique view of SARS-CoV-2 through the lens of ORF8 protein date: 2020-08-26 words: 5942.0 sentences: 322.0 pages: flesch: 55.0 cache: ./cache/cord-338055-2d6n4cve.txt txt: ./txt/cord-338055-2d6n4cve.txt summary: In this present study, we identified the distinct mutations present across unique variants of the SARS-CoV-2 ORF8 and classified them according to their predicted effect on the host, i.e disease or neutral and the consequences on protein structural stability. The ORF8 sequences of SARS-CoV-2, Bat-CoV RaTG13 and Pangolin-CoV have almost the same positive and negative charged amino acids, therefore we can say that probably they have similar kind of electrostatic and hydrophobic interactions, 135 which also contribute to the functionality of the proteins. • QKV07730.1: The T11A mutation occurred as the second mutation in this sequence, which was predicted to be of disease-increasing type and the polarity was changed from hydrophilic to hydrophobic, hence the structure and 305 function of the protein are expected to differ. abstract: Immune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through downregulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geolocations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8. url: https://doi.org/10.1101/2020.08.25.267328 doi: 10.1101/2020.08.25.267328 id: cord-102935-cx3elpb8 author: Hassani-Pak, Keywan title: KnetMiner: a comprehensive approach for supporting evidence-based gene discovery and complex trait analysis across species date: 2020-04-24 words: 2172.0 sentences: 119.0 pages: flesch: 60.0 cache: ./cache/cord-102935-cx3elpb8.txt txt: ./txt/cord-102935-cx3elpb8.txt summary: Here we report the main design principles behind KnetMiner and provide use cases for mining public datasets to identify unknown links between traits such grain colour and pre-harvest sprouting in Triticum aestivum, as well as, an evidence-based approach to identify candidate genes under an Arabidopsis thaliana petal size QTL. KnetMiner is the first open-source gene discovery platform that can leverage genome-scale knowledge graphs, generate evidence-based biological networks and be deployed for any species with a sequenced genome. Even when 38 the task of gathering information is complete, it is demanding to assemble a coherent view of how 39 each piece of evidence might come together to "tell a story" about the biology that can explain how 40 multiple genes might be implicated in a complex trait or disease. abstract: Generating new ideas and scientific hypotheses is often the result of extensive literature and database reviews, overlaid with scientists’ own novel data and a creative process of making connections that were not made before. We have developed a comprehensive approach to guide this technically challenging data integration task and to make knowledge discovery and hypotheses generation easier for plant and crop researchers. KnetMiner can digest large volumes of scientific literature and biological research to find and visualise links between the genetic and biological properties of complex traits and diseases. Here we report the main design principles behind KnetMiner and provide use cases for mining public datasets to identify unknown links between traits such grain colour and pre-harvest sprouting in Triticum aestivum, as well as, an evidence-based approach to identify candidate genes under an Arabidopsis thaliana petal size QTL. We have developed KnetMiner knowledge graphs and applications for a range of species including plants, crops and pathogens. KnetMiner is the first open-source gene discovery platform that can leverage genome-scale knowledge graphs, generate evidence-based biological networks and be deployed for any species with a sequenced genome. KnetMiner is available at http://knetminer.org. url: https://doi.org/10.1101/2020.04.02.017004 doi: 10.1101/2020.04.02.017004 id: cord-329840-f3dsu36p author: Hati, Sanchita title: Impact of Thiol-Disulfide Balance on the Binding of Covid-19 Spike Protein with Angiotensin Converting Enzyme 2 Receptor date: 2020-05-11 words: 2497.0 sentences: 173.0 pages: flesch: 51.0 cache: ./cache/cord-329840-f3dsu36p.txt txt: ./txt/cord-329840-f3dsu36p.txt summary: In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. In the backdrop of significant mortality rate for SARS-CoV-2 (hereinafter referred to as CoV-2) infection, it is important to know if the thiol-disulfide balance plays any role on the binding of the spike glycoprotein on to the host cell receptor protein ACE2. Using these reported structures, molecular dynamics simulations and electrostatic field calculations were performed to explore the impact of thioldisulfide balance on CoV/CoV-2 and ACE2 binding affinities. The structural and dynamical changes due to the change in the redox states of cysteines in the interacting proteins were analyzed and their effects on binding free energies were studied. abstract: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease (COVID-19), which started in 2019. This is a member of Coronaviridae family in the genus Betacoronavirus, which also includes SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). The angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV and SARS-CoV-2 to enter the host cells. In particular, the interaction of viral spike proteins with ACE2 is a critical step in the viral replication cycle. The receptor binding domain of the viral spike proteins and ACE2 have several cysteine residues. In this study, the role of thiol-disulfide balance on the interactions between SARS-CoV/CoV-2 spike proteins and ACE2 was investigated using molecular dynamic simulations. The study revealed that the binding affinity was significantly impaired when all the disulfide bonds of both ACE2 and SARS-CoV/CoV-2 spike proteins were reduced to thiol groups. The impact on the binding affinity was less severe when the disulfide bridges of only one of the binding partners were reduced to thiols. This computational finding provides a molecular basis for the severity of COVID-19 infection due to the oxidative stress. url: https://doi.org/10.1101/2020.05.07.083147 doi: 10.1101/2020.05.07.083147 id: cord-334624-chnibsa1 author: Hayn, Manuel title: Imperfect innate immune antagonism renders SARS-CoV-2 vulnerable towards IFN-γ and -λ date: 2020-10-30 words: 5355.0 sentences: 432.0 pages: flesch: 57.0 cache: ./cache/cord-334624-chnibsa1.txt txt: ./txt/cord-334624-chnibsa1.txt summary: Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation. SARS-CoV-1 ORF6 is about 4-fold less potent in antagonizing type I IFN signaling (Fig. 243 4b) but induces higher levels of autophagy (Fig. 4c) . Examination of the functional conservation showed that SARS-CoV-2 Nsp15 was less 319 efficient in blocking innate immune activation, both type I IFN induction and signaling, than SARS-320 Hepatitis C virus viruses to block anti-viral autophagic turnover 50 and thus may represent a common studies will see more mechanistic data to explain the molecular details of the impact of SARS-CoV-2 343 proteins on innate immune activation. abstract: The innate immune system constitutes a powerful barrier against viral infections. However, it may fail because successful emerging pathogens, like SARS-CoV-2, evolved strategies to counteract it. Here, we systematically assessed the impact of 29 SARS-CoV-2 proteins on viral sensing, type I, II and III interferon (IFN) signaling, autophagy and inflammasome formation. Mechanistic analyses show that autophagy and type I IFN responses are effectively counteracted at different levels. For example, Nsp14 induces loss of the IFN receptor, whereas ORF3a disturbs autophagy at the Golgi/endosome interface. Comparative analyses revealed that antagonism of type I IFN and autophagy is largely conserved, except that SARS-CoV-1 Nsp15 is more potent in counteracting type I IFN than its SARS-CoV-2 ortholog. Altogether, however, SARS-CoV-2 counteracts type I IFN responses and autophagy much more efficiently than type II and III IFN signaling. Consequently, the virus is relatively resistant against exogenous IFN-α/β and autophagy modulation but remains highly vulnerable towards IFN-γ and -λ treatment. In combination, IFN-γ and -λ act synergistically, and drastically reduce SARS-CoV-2 replication at exceedingly low doses. Our results identify ineffective type I and II antagonism as weakness of SARS-CoV-2 that may allow to devise safe and effective anti-viral therapies based on targeted innate immune activation. url: https://doi.org/10.1101/2020.10.15.340612 doi: 10.1101/2020.10.15.340612 id: cord-254855-gmy9zyad author: He, Sijia title: PSGL-1 inhibits the virion incorporation of SARS-CoV and SARS-CoV-2 spike glycoproteins and impairs virus attachment and infectivity date: 2020-07-06 words: 1700.0 sentences: 94.0 pages: flesch: 51.0 cache: ./cache/cord-254855-gmy9zyad.txt txt: ./txt/cord-254855-gmy9zyad.txt summary: Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks virus attachment and infection of target cells. Together, these results demonstrate that PSGL-1 expression in the virus-producer cells severely diminishes the infectivity of virions bearing SARS coronavirus S proteins. We and other previously reported that PSGL-1-mediated inhibition of virion infectivity is through steric hindrance of particle attachment to target cells, which does not depend on the presence of viral envelope glycoproteins (1, 5) . We performed a virion attachment assay and observed that the lentiviral particles pseudotyped with SARS-CoV or SARS-CoV-2 S protein produced from PSGL-1-expressing cells were impaired in their ability to attach to target cells (Fig. 2D) . These results demonstrate that the presence of PSGL-1 on virus particles can structurally hinder virion interaction with the target cells even in the presence of remaining S proteins, consistent with previous studies of PSGL-1 and HIV-1 infection (1, 5) . abstract: P-selectin glycoprotein ligand-1 (PSGL-1) is a cell surface glycoprotein that binds to P-, E-, and L-selectins to mediate the tethering and rolling of immune cells on the surface of the endothelium for cell migration into inflamed tissues. PSGL-1 has been identified as an interferon-γ (INF-γ)-regulated factor that restricts HIV-1 infectivity, and has recently been found to possess broad-spectrum antiviral activities. Here we report that the expression of PSGL-1 in virus-producing cells impairs the incorporation of SARS-CoV and SARS-CoV-2 spike (S) glycoproteins into pseudovirions and blocks virus attachment and infection of target cells. These findings suggest that PSGL-1 may potentially inhibit coronavirus replication in PSGL-1+ cells. url: https://www.ncbi.nlm.nih.gov/pubmed/32511349/ doi: 10.1101/2020.05.01.073387 id: cord-323908-8dgngwmw author: He, Zhesheng title: Molecules inhibit the enzyme activity of 3-chymotrypsin-like cysteine protease of SARS-CoV-2 virus: the experimental and theory studies date: 2020-05-31 words: 881.0 sentences: 61.0 pages: flesch: 59.0 cache: ./cache/cord-323908-8dgngwmw.txt txt: ./txt/cord-323908-8dgngwmw.txt summary: title: Molecules inhibit the enzyme activity of 3-chymotrypsin-like cysteine protease of SARS-CoV-2 virus: the experimental and theory studies Herein, we report that the clinical approved auranofin could perfectly inhibit the activity of 3-chymotrypsin-like cysteine protease (Mpro or 3CLpro) of SARS-CoV-2. As Au(I) ion is active metabolism specie derived from gold compounds or gold clusters in vivo, further computational studies revealed Au ion could tightly bind thiol group of Cys145 residue of 3CLpro thus inhibit enzyme activity. Also, phenyl isothiocyanate and Vitamin K3 may interact with thiol group of Cys145 via Michael addition reaction, molecular dynamic (MD) theory studied are applied to confirmed these small molecules are stable in the pocket and inhibit Mpro activity. These compounds could serve as potential anti-SARS-CoV-2 lead molecules for further drug studies to combat COVID-19. The interactions between the gold atom with the binding pockets of proteins were studied by density functional theory (DFT) calculations. abstract: SARS-CoV-2 has emerged as a world public health threat. Herein, we report that the clinical approved auranofin could perfectly inhibit the activity of 3-chymotrypsin-like cysteine protease (Mpro or 3CLpro) of SARS-CoV-2. Gold cluster could significantly inhibit 3CLpro of SARS-COV-2. Phenyl isothiocyanate and Vitamin K3 could well suppress the activity of 3CLpro. For Mpro inhibition, IC50 of auranofin, Vitamin K3, phenyl isothiocyanate, gold cluster are about 0.51μM, 7.96μM, 10.13μM, 1.61μM, respectively. These compounds may be with potentials for treatment SARS-CoV-2 virus replication. Especially for FDA approved auranofin, it is an anti-inflammation drug in clinic, thus it may with strong potential to inhibit virus replication and suppress the inflammation damage in COVID-19 patients. Gold cluster is with better safety index and well anti-inflammation in vitro/vivo, therefore it is with potential to inhibit virus replication and suppress the inflammation damage caused by COVID-19 virus. As Au(I) ion is active metabolism specie derived from gold compounds or gold clusters in vivo, further computational studies revealed Au ion could tightly bind thiol group of Cys145 residue of 3CLpro thus inhibit enzyme activity. Also, phenyl isothiocyanate and Vitamin K3 may interact with thiol group of Cys145 via Michael addition reaction, molecular dynamic (MD) theory studied are applied to confirmed these small molecules are stable in the pocket and inhibit Mpro activity. url: https://doi.org/10.1101/2020.05.28.120642 doi: 10.1101/2020.05.28.120642 id: cord-353731-7xn7m662 author: Heaton, Brook E. title: SRSF protein kinases 1 and 2 are essential host factors for human coronaviruses including SARS-CoV-2 date: 2020-08-18 words: 2233.0 sentences: 139.0 pages: flesch: 51.0 cache: ./cache/cord-353731-7xn7m662.txt txt: ./txt/cord-353731-7xn7m662.txt summary: sgRNA sequencing data indicated that the host gene with the highest probability of being 125 required for SARS-CoV-2 infection was the serine/arginine-rich protein kinase, SRPK1 126 ( Figure 1B) . We next wanted to define the degree to which inhibition of SRPK1 mediated N 141 phosphorylation would affect viral replication, especially since other non-SRPK1 kinases 142 have been predicted to be responsible for SARS-CoV-2 protein phosphorylation 12,13 . SRPIN340 treatment of cells infected with the 183 alphacoronavirus 229E (which is only distantly related to betacoronavirus SARS-CoV-2) 184 inhibited the virus by more than 1,000-fold at non-toxic concentrations of the drug ( Figure 185 2G-H). Human papillomavirus type 1 E1^E4 protein is a potent 533 inhibitor of the serine-arginine (SR) protein kinase SRPK1 and inhibits 534 phosphorylation of host SR proteins and of the viral transcription and replication 535 regulator E2 abstract: Antiviral therapeutics against SARS-CoV-2 are needed to treat the pandemic disease COVID-19. Pharmacological targeting of a host factor required for viral replication can suppress viral spread with a low probability of viral mutation leading to resistance. Here, we performed a genome-wide screen in human lung epithelial cells to identify potential host therapeutic targets. We report that the kinase SRPK1, together with the closely related SRPK2, are jointly essential for SARS-CoV-2 replication; inhibition of SRPK1/2 with small molecules led to a dramatic decrease (more than 100,000-fold) in SARS-CoV-2 virus production in immortalized and primary human lung cells. Subsequent biochemical studies revealed that SPRK1/2 phosphorylate the viral nucleocapsid (N) protein at sites highly conserved across human coronaviruses and, due to this conservation, even a distantly related coronavirus was highly sensitive to an SPRK1/2 inhibitor. Together, these data suggest that SRPK1/2-targeted therapies may be an efficacious strategy to prevent or treat COVID-19 and other coronavirus-mediated diseases. url: https://doi.org/10.1101/2020.08.14.251207 doi: 10.1101/2020.08.14.251207 id: cord-295545-ruxz77i8 author: Hennighausen, Lothar title: Activation of the SARS-CoV-2 receptor Ace2 by cytokines through pan JAK-STAT enhancers date: 2020-05-11 words: 1660.0 sentences: 108.0 pages: flesch: 55.0 cache: ./cache/cord-295545-ruxz77i8.txt txt: ./txt/cord-295545-ruxz77i8.txt summary: The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. The presence of pan JAK-STAT components in mammary alveolar cells and in Type II Pneumocytes combined with the autoregulation of both STAT1 and STAT5 suggests a prominent role of cytokine signaling pathways in cells targeted by SARS-CoV-2. A study in pneumocytes demonstrated that ACE2 expression is induced by interferons (Ziegler, 2020) , possibly through the transcription factors Signal Transducer and Activator of Transcription (STAT) 1 and 2, as the authors suggest. Ace2 mRNA levels vary widely between cell types, with high expression detected in lactating mammary and intestinal tissues ( Figure 1A -B) and Type II Pneumocytes (Ziegler, 2020) . To explore the possibility that Ace2 gene expression in SARS-CoV-2 target cells is regulated not only by interferons but also by a range of cytokines through the family of STAT transcription factors, we mined available scRNA-seq data (Ziegler, 2020) (Table 1) . abstract: ACE2, in concert with the protease TMPRSS2, binds the novel coronavirus SARS-CoV-2 and facilitates its cellular entry. The ACE2 gene is expressed in SARS-CoV-2 target cells, including Type II Pneumocytes (Ziegler, 2020), and is activated by interferons. Viral RNA was also detected in breast milk (Wu et al., 2020), raising the possibility that ACE2 expression is under the control of cytokines through the JAK-STAT pathway. Here we show that Ace2 expression in mammary tissue is induced during pregnancy and lactation, which coincides with the establishment of a candidate enhancer. The prolactin-activated transcription factor STAT5 binds to tandem sites that coincide with activating histone enhancer marks and additional transcription components. The presence of pan JAK-STAT components in mammary alveolar cells and in Type II Pneumocytes combined with the autoregulation of both STAT1 and STAT5 suggests a prominent role of cytokine signaling pathways in cells targeted by SARS-CoV-2. url: https://doi.org/10.1101/2020.05.11.089045 doi: 10.1101/2020.05.11.089045 id: cord-103502-asphso2s author: Herrgårdh, Tilda title: An organ-based multi-level model for glucose homeostasis: organ distributions, timing, and impact of blood flow date: 2020-10-21 words: 8160.0 sentences: 409.0 pages: flesch: 60.0 cache: ./cache/cord-103502-asphso2s.txt txt: ./txt/cord-103502-asphso2s.txt summary: Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. However, neither this model, nor any of the previously mentioned multi-level models, have subdivided the glucose uptake into the individual contributions of all of the main insulin-responding and glucose-utilizing organs: adipose tissue, muscle, and liver. The final combined model (Q4) can fit to all of the new data for glucose uptake in all organs (Fig 6) , as well as to all previous data, such as the postprandial glucose and insulin fluxes and concentrations in (Dalla Man et al. abstract: Glucose homeostasis is the tight control of glucose in the blood. This complex control is important and not yet sufficiently understood, due to its malfunction in serious diseases like diabetes. Due to the involvement of numerous organs and sub-systems, each with their own intra-cellular control, we have developed a multi-level mathematical model, for glucose homeostasis, which integrates a variety of data. Over the last 10 years, this model has been used to insert new insights from the intra-cellular level into the larger whole-body perspective. However, the original cell-organ-body translation has during these years never been updated, despite several critical shortcomings, which also have not been resolved by other modelling efforts. For this reason, we here present an updated multi-level model. This model provides a more accurate sub-division of how much glucose is being taken up by the different organs. Unlike the original model, we now also account for the different dynamics seen in the different organs. The new model also incorporates the central impact of blood flow on insulin-stimulated glucose uptake. Each new improvement is clear upon visual inspection, and they are also supported by statistical tests. The final multi-level model describes >300 data points in >40 time-series and dose-response curves, resulting from a large variety of perturbations, describing both intra-cellular processes, organ fluxes, and whole-body meal responses. We hope that this model will serve as an improved basis for future data integration, useful for research and drug developments within diabetes. url: https://doi.org/10.1101/2020.10.21.344499 doi: 10.1101/2020.10.21.344499 id: cord-296657-mymndjvd author: Higuchi, Yusuke title: High affinity modified ACE2 receptors prevent SARS-CoV-2 infection date: 2020-09-16 words: 3509.0 sentences: 195.0 pages: flesch: 51.0 cache: ./cache/cord-296657-mymndjvd.txt txt: ./txt/cord-296657-mymndjvd.txt summary: The extracellular domain of modified ACE2 fused to the Fc region of the human immunoglobulin IgG1 had stable structure and neutralized SARS-CoV-2 pseudotyped lentivirus and authentic virus with more than 100-fold lower concentration than wild-type. Engineering ACE2 decoy receptors with directed evolution is a promising approach to develop a SARS-CoV-2 neutralizing drug that has affinity comparable to monoclonal antibodies yet displaying resistance to escape mutations of virus. Three cycles of screening resulted in an identification of mutant ACE2 clones with more than 100-fold higher binding affinity to the RBD and lower half-maximal inhibitory concentration (IC50) for SARS-CoV-2 pseudotyped lentivirus as well as authentic virus. We engineered ACE2 to bind the RBD of the SARS-CoV-2 spike protein with the combination of surface display of mutagenized library and fluorescence-activated cell sorting (FACS) to perform the evolution in 293T human cells. abstract: The SARS-CoV-2 spike protein binds to the human angiotensin-converting enzyme 2 (ACE2) receptor via receptor binding domain (RBD) to enter into the cell. Inhibiting this interaction is a main approach to block SARS-CoV-2 infection and it is required to have high affinity to RBD independently of viral mutation for effective protection. To this end, we engineered ACE2 to enhance the affinity with directed evolution in human cells. Three cycles of random mutation and cell sorting achieved more than 100-fold higher affinity to RBD than wild-type ACE2. The extracellular domain of modified ACE2 fused to the Fc region of the human immunoglobulin IgG1 had stable structure and neutralized SARS-CoV-2 pseudotyped lentivirus and authentic virus with more than 100-fold lower concentration than wild-type. Engineering ACE2 decoy receptors with directed evolution is a promising approach to develop a SARS-CoV-2 neutralizing drug that has affinity comparable to monoclonal antibodies yet displaying resistance to escape mutations of virus. url: https://doi.org/10.1101/2020.09.16.299891 doi: 10.1101/2020.09.16.299891 id: cord-103925-i73ymrov author: Hill, Chris H. title: Structural and molecular basis for protein-stimulated ribosomal frameshifting in Theiler’s murine encephalomyelitis virus date: 2020-08-11 words: 11552.0 sentences: 550.0 pages: flesch: 53.0 cache: ./cache/cord-103925-i73ymrov.txt txt: ./txt/cord-103925-i73ymrov.txt summary: Finally, we use metabolic labelling and ribosome profiling to study 2A-mediated frameshifting and translation of the TMEV genome at sub-codon resolution in infected cells. A meta-analysis of the inferred P site positions of ribosomes relative to host mRNA start and stop codons reveals that RPFs map to coding sequences with a triplet periodicity reflective of the length of a codon ( Figure S3D ). Moving on to look specifically at the frameshift site, a single-nucleotide resolution plot of reads mapping to this region reveals a peak on the SS mutant genome corresponding to a ribosome paused with the GUU codon of the slippery sequence in the P site ( Figure 5G , Figure S4C ). These read lengths were selected for analysis as potential "disome-protected fragments", and their density plotted on the viral genome at the inferred P site position of the upstream, colliding ribosome ( Figure 6C and D). abstract: The 2A protein of Theiler’s murine encephalomyelitis virus (TMEV) is required for stimulating programmed −1 ribosomal frameshifting (PRF) during infection. However, the amino acid sequence of TMEV 2A shares only 27% identity with the 2A orthologue from the related cardiovirus encephalomyocarditis virus (EMCV) for which a structure has been recently determined. Here we present the X-ray crystal structure of TMEV 2A, revealing that, despite the low sequence identity, the overall beta-shell architecture is retained, and the location of previously described mutations on this structure suggests a common RNA binding mode. We determine the minimal stimulatory element in the viral RNA required for 2A binding and show that 2A binds to this element with 1:1 stoichiometry and nanomolar affinity. We also demonstrate a critical role for bases upstream of the originally predicted stem-loop, providing evidence that an alternative pseudoknot-like conformation recently demonstrated for EMCV is a conserved feature of cardiovirus stimulatory elements. We go on to examine frameshifting in infected cells by ribosome profiling and metabolic labelling. We observe PRF efficiencies of up to 85%, highlighting this as the most efficient example of −1 PRF in any natural system thus far characterised. Furthermore, we document a series of ribosomal pauses in and around the site of PRF with potential implications for our understanding of translational control in cardioviruses. url: https://doi.org/10.1101/2020.08.11.245068 doi: 10.1101/2020.08.11.245068 id: cord-328960-46zui1sl author: Hillen, Hauke S. title: Structure of replicating SARS-CoV-2 polymerase date: 2020-04-27 words: 4541.0 sentences: 285.0 pages: flesch: 62.0 cache: ./cache/cord-328960-46zui1sl.txt txt: ./txt/cord-328960-46zui1sl.txt summary: Particle classification yielded a 3D reconstruction at a nominal resolution of 2.9 Å and led to a refined structure of the RdRp-RNA complex (Extended Data Figures 1 and 2) . The structure resembles that of the free enzyme 16 , but also reveals large additional protein regions in nsp8 that became ordered upon RNA binding and interact with RNA far outside the core enzyme (Extended Data Figure 3a ). The supernatant containing nsp12 was filtered using a 5-μm syringe filter, followed by filtration with a 0.8-µm syringe filter (Millipore) and applied onto a HisTrap HP 5 mL (GE Healthcare), preequilibrated in lysis buffer (300 mM NaCl, 50 mM Na-HEPES pH 7.4, 10 % (v/v) glycerol, 30 mM imidazole pH 8.0, 3 mM MgCl2, 5 mM β-mercaptoethanol, 0.284 µg ml-1 leupeptin, 1.37 µg ml-1 pepstatin, 0.17 mg ml-1 PMSF, and 0.33 mg ml-1 benzamidine). abstract: The coronavirus SARS-CoV-2 uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes. Here we present the cryo-electron microscopic structure of the SARS-CoV-2 RdRp in its replicating form. The structure comprises the viral proteins nsp12, nsp8, and nsp7, and over two turns of RNA template-product duplex. The active site cleft of nsp12 binds the first turn of RNA and mediates RdRp activity with conserved residues. Two copies of nsp8 bind to opposite sides of the cleft and position the RNA duplex as it exits. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged ‘sliding poles’ that may enable processive replication of the long coronavirus genome. Our results will allow for a detailed analysis of the inhibitory mechanisms used by antivirals such as remdesivir, which is currently in clinical trials for the treatment of coronavirus disease 2019 (COVID-19). url: https://doi.org/10.1101/2020.04.27.063180 doi: 10.1101/2020.04.27.063180 id: cord-342456-5gp3cry0 author: Hoagland, Daisy A. title: Modulating the transcriptional landscape of SARS-CoV-2 as an effective method for developing antiviral compounds date: 2020-07-13 words: 4511.0 sentences: 240.0 pages: flesch: 48.0 cache: ./cache/cord-342456-5gp3cry0.txt txt: ./txt/cord-342456-5gp3cry0.txt summary: Utilizing expression patterns of SARS-CoV-2-infected cells, we identified a region in gene expression space that was unique to virus infection and inversely proportional to the transcriptional footprint of known compounds characterized in the Library of Integrated Network-based Cellular Signatures. These signatures were then used as queries against the LINCS L1000 dataset, a collection of gene expression profiles generated following the administration of >20,000 bioactive compounds including >1,000 FDA-approved drugs to human cell lines at a variety of different times and concentrations (Subramanian et al., 2017) With L1000FWD , we could identify reciprocal transcriptional signatures generated between SARS-CoV-2 infection and a given compound. Overall, based on the L1000 data, these seven compounds influence the same pharmacological high-dimensional gene expression signature space and are predicted to disrupt key cellular processes that are modulated in response to SARS-CoV-2 infection. abstract: To interfere with the biology of SARS-CoV-2, the virus responsible for the COVID-19 pandemic, we focused on restoring the transcriptional response induced by infection. Utilizing expression patterns of SARS-CoV-2-infected cells, we identified a region in gene expression space that was unique to virus infection and inversely proportional to the transcriptional footprint of known compounds characterized in the Library of Integrated Network-based Cellular Signatures. Here we demonstrate the successful identification of compounds that display efficacy in blocking SARS-CoV-2 replication based on their ability to counteract the virus-induced transcriptional landscape. These compounds were found to potently reduce viral load despite having no impact on viral entry or modulation of the host antiviral response in the absence of virus. RNA-Seq profiling implicated the induction of the cholesterol biosynthesis pathway as the underlying mechanism of inhibition and suggested that targeting this aspect of host biology may significantly reduce SARS-CoV-2 viral load. url: https://doi.org/10.1101/2020.07.12.199687 doi: 10.1101/2020.07.12.199687 id: cord-350817-tmszrtju author: Hoepel, Willianne title: Anti-SARS-CoV-2 IgG from severely ill COVID-19 patients promotes macrophage hyper-inflammatory responses date: 2020-07-13 words: 5626.0 sentences: 296.0 pages: flesch: 47.0 cache: ./cache/cord-350817-tmszrtju.txt txt: ./txt/cord-350817-tmszrtju.txt summary: Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. Taken together, these data demonstrate that anti-Spike IgG immune complexes generated from serum of severely ill COVID-19 patients induce a strong pro-inflammatory response by (otherwise immunosuppressive) human M2 macrophages, which is characterized by high production of classical cytokine storm mediators such as IL-1β, IL-6, IL-8, and TNF. As shown in Figure 4A , the used human macrophage model highly expressed all FcγRs. To determine whether FcγRs are involved in activation by anti-Spike immune complexes, we blocked the different FcγRs with specific antibodies during stimulation, and analyzed cytokine production. In conclusion, our data show that anti-Spike IgG from serum of severely ill COVID-19 patients strongly amplifies pro-inflammatory responses by human macrophages, and can contribute to subsequent endothelial barrier disruption and thrombosis. abstract: For yet unknown reasons, severely ill COVID-19 patients often become critically ill around the time of activation of adaptive immunity. Here, we show that anti-Spike IgG from serum of severely ill COVID-19 patients induces a hyper-inflammatory response by human macrophages, which subsequently breaks pulmonary endothelial barrier integrity and induces microvascular thrombosis. The excessive inflammatory capacity of this anti-Spike IgG is related to glycosylation changes in the IgG Fc tail. Moreover, the hyper-inflammatory response induced by anti-Spike IgG can be specifically counteracted in vitro by use of the active component of fostamatinib, an FDA- and EMA-approved therapeutic small molecule inhibitor of Syk. One sentence summary Anti-Spike IgG promotes hyper-inflammation. url: https://doi.org/10.1101/2020.07.13.190140 doi: 10.1101/2020.07.13.190140 id: cord-327431-dnppshnv author: Hognon, Cécilia title: Role of RNA Guanine Quadruplexes in Favoring the Dimerization of SARS Unique Domain in Coronaviruses date: 2020-05-27 words: 2460.0 sentences: 133.0 pages: flesch: 48.0 cache: ./cache/cord-327431-dnppshnv.txt txt: ./txt/cord-327431-dnppshnv.txt summary: In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. 28, 37 In this letter, we report an extended all-atom molecular dynamics (MD) study of the interactions produced between a dimeric SUD domain and a short RNA G4 sequence. To further examine the conformational space spanned by the G4/SUD complex, and in particular the role of the RNA in favoring the dimerization and the structure of the interface, we resorted to enhanced sampling MD simulations to obtain the 2D free energy profile along two relevant collective variables: first, the distance between G4 and SUD, and second, the separation between the two SUD subdomains. abstract: Coronaviruses may produce severe acute respiratory syndrome (SARS). As a matter of fact, a new SARS-type virus, SARS-CoV-2, is responsible of a global pandemic in 2020 with unprecedented sanitary and economic consequences for most countries. In the present contribution we study, by all-atom equilibrium and enhanced sampling molecular dynamics simulations, the interaction between the SARS Unique Domain and RNA guanine quadruplexes, a process involved in eluding the defensive response of the host thus favoring viral infection of human cells. Our results evidence two stable binding modes involving an interaction site spanning either the protein dimer interface or only one monomer. The free energy profile unequivocally points to the dimer mode as the thermodynamically favored one. The effect of these binding modes in stabilizing the protein dimer was also assessed, being related to its biological role in assisting SARS viruses to bypass the host protective response. This work also constitutes a first step of the possible rational design of efficient therapeutic agents aiming at perturbing the interaction between SARS Unique Domain and guanine quadruplexes, hence enhancing the host defenses against the virus. TOC GRAPHICS url: https://doi.org/10.1101/2020.04.07.029447 doi: 10.1101/2020.04.07.029447 id: cord-264919-0jlg2gkc author: Hopp, Marie-Thérèse title: Unravelling the debate on heme effects in COVID-19 infections date: 2020-06-12 words: 7093.0 sentences: 366.0 pages: flesch: 49.0 cache: ./cache/cord-264919-0jlg2gkc.txt txt: ./txt/cord-264919-0jlg2gkc.txt summary: On the one hand, we examine the possibility of a direct interaction of heme with select SARS-CoV-2 proteins and specific host cell proteins by applying our webserver HeMoQuest (Paul that is based on experimental data. One of the most promising findings was the prediction of heme-binding motifs (HBMs) in the host cell proteins ACE2 and TMPRSS2. We leveraged this multimodal information to hypothesize the pathways that connect key molecules associated with SARS-CoV-2 and heme to phenotypes observed in COVID-19 patients. Here, we have investigated the possibility of a direct interaction of heme with SARS-CoV-2 surface proteins and their human counterparts ACE2 and TMPRSS2. Apart from investigating the direct impact of heme on proteins at the interface of the virus-host cell interaction, we also explored similarities between relevant pathways characterizing the respective pathologies, i.e. labile heme occurrence in hemolytic conditions and COVID-19 disease progression ( Figure 4) . abstract: The SARS-CoV-2 outbreak was recently declared a worldwide pandemic. Infection triggers the respiratory tract disease COVID-19, which is accompanied by serious changes of clinical biomarkers such as hemoglobin and interleukins. The same parameters are altered during hemolysis, which is characterized by an increase in labile heme. We present two approaches that aim at analyzing a potential link between available heme and COVID-19 pathogenesis. Four COVID-19 related proteins, i.e. the host cell proteins ACE2 and TMPRSS2 as well as the viral protein 7a and S protein, were identified as potential heme binders. We also performed a detailed analysis of the common pathways induced by heme and SARS-CoV-2 by superimposition of knowledge graphs covering heme biology and COVID-19 pathophysiology. Herein, focus was laid on inflammatory pathways, and distinct biomarkers as the linking elements. Finally, the results substantially improve our understanding of COVID-19 infections and disease progression of patients with different clinical backgrounds and expand the diagnostic and treatment options. url: https://doi.org/10.1101/2020.06.09.142125 doi: 10.1101/2020.06.09.142125 id: cord-297775-ug4ovsws author: Hosie, Margaret J title: Respiratory disease in cats associated with human-to-cat transmission of SARS-CoV-2 in the UK date: 2020-09-23 words: 1997.0 sentences: 118.0 pages: flesch: 54.0 cache: ./cache/cord-297775-ug4ovsws.txt txt: ./txt/cord-297775-ug4ovsws.txt summary: High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. Recent reports from Dutch mink farms of both mink-to-cat and mink-tohuman transmission of the virus provide support for this scenario (5, 9) We used a range of laboratory techniques to show that two domestic cats from households with suspected cases of COVID-19, and which displayed either mild or severe respiratory disease, were infected with SARS-CoV-2. As we do not have the owner''s virus sequence, we cannot determine whether the observed mutations in cat 2''s viral genome arose in a human prior to transmission. Table 1 details the SNPs observed in the cat 2 viral genome, and their frequency in the existing UK human population and among existing feline SARS-CoV-2 sequences. abstract: Two cats from different COVID-19-infected households in the UK were found to be infected with SARS-CoV-2 from humans, demonstrated by immunofluorescence, in situ hybridisation, reverse transcriptase quantitative PCR and viral genome sequencing. Lung tissue collected post-mortem from cat 1 displayed pathological and histological findings consistent with viral pneumonia and tested positive for SARS-CoV-2 antigens and RNA. SARS-CoV-2 RNA was detected in an oropharyngeal swab collected from cat 2 that presented with rhinitis and conjunctivitis. High throughput sequencing of the virus from cat 2 revealed that the feline viral genome contained five single nucleotide polymorphisms (SNPs) compared to the nearest UK human SARS-CoV-2 sequence. An analysis of cat 2’s viral genome together with nine other feline-derived SARS-CoV-2 sequences from around the world revealed no shared catspecific mutations. These findings indicate that human-to-cat transmission of SARS-CoV-2 occurred during the COVID-19 pandemic in the UK, with the infected cats developing mild or severe respiratory disease. Given the versatility of the new coronavirus, it will be important to monitor for human-to-cat, cat-to-cat and cat-to-human transmission. url: https://doi.org/10.1101/2020.09.23.309948 doi: 10.1101/2020.09.23.309948 id: cord-339012-4juhmjaj author: Hou, Wei title: Rapid host response to an infection with Coronavirus. Study of transcriptional responses with Porcine Epidemic Diarrhea Virus date: 2020-07-28 words: 6756.0 sentences: 344.0 pages: flesch: 48.0 cache: ./cache/cord-339012-4juhmjaj.txt txt: ./txt/cord-339012-4juhmjaj.txt summary: Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and "synaptic clefts" between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The detected sets of differential expressed genes (DEGs) for PEDV and MRV were analyzed by gene set enrichment analysis (GSEA) using functional bioinformatic programs to retrieve biological processes (pathways and Gene Ontology terms [GO-term]) and associations with chemical compounds, including drugs. abstract: The transcriptional response in Vero cells (ATCC® CCL-81) infected with the coronavirus Porcine Epidemic Diarrhea Virus (PEDV) was measured by RNAseq analysis 4 and 6 hours after infection. Differential expressed genes (DEGs) in PEDV infected cells were compared to DEGs responding in Vero cells infected with Mammalian Orthoreovirus (MRV). Functional analysis of MRV and PEDV DEGs showed that MRV increased the expression level of several cytokines and chemokines (e.g. IL6, CXCL10, IL1A, CXCL8 [alias IL8]) and antiviral genes (e.g. IFI44, IFIT1, MX1, OASL), whereas for PEDV no enhanced expression was observed for these “hallmark” antiviral and immune effector genes. Pathway and Gene Ontology “enrichment analysis” revealed that PEDV infection did not stimulate expression of genes able to activate an acquired immune response, whereas MRV did so within 6h. Instead, PEDV down-regulated the expression of a set of zinc finger proteins with putative antiviral activity and enhanced the expression of the transmembrane serine protease gene TMPRSS13 (alias MSPL) to support its own infection by virus-cell membrane fusion (Shi et al, 2017, Viruses, 9(5):114). PEDV also down-regulated expression of Ectodysplasin A, a cytokine of the TNF-family able to activate the canonical NFKB-pathway responsible for transcription of inflammatory genes like IL1B, TNF, CXCL8 and PTGS2. The only 2 cytokine genes found up-regulated by PEDV were Cardiotrophin-1, an IL6-type cytokine with pleiotropic functions on different tissues and types of cells, and Endothelin 2, a neuroactive peptide with vasoconstrictive properties. Furthermore, by comprehensive datamining in biological and chemical databases and consulting related literature we identified sets of PEDV-response genes with potential to influence i) the metabolism of biogenic amines (e.g. histamine), ii) the formation of cilia and “synaptic clefts” between cells, iii) epithelial mucus production, iv) platelets activation, and v) physiological processes in the body regulated by androgenic hormones (like blood pressure, salt/water balance and energy homeostasis). The information in this study describing a “very early” response of epithelial cells to an infection with a coronavirus may provide pharmacologists, immunological and medical specialists additional insights in the underlying mechanisms of coronavirus associated severe clinical symptoms including those induced by SARS-CoV-2. This may help them to fine-tune therapeutic treatments and apply specific approved drugs to treat COVID-19 patients. url: https://doi.org/10.1101/2020.07.28.224576 doi: 10.1101/2020.07.28.224576 id: cord-302608-fw4pmaoc author: Huang, Jiao-Mei title: Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) date: 2020-03-19 words: 1890.0 sentences: 125.0 pages: flesch: 57.0 cache: ./cache/cord-302608-fw4pmaoc.txt txt: ./txt/cord-302608-fw4pmaoc.txt summary: However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. The host specificity of virus particle is determined by amino acid sequence of RBD and is usually dissimilar among different CoVs. Therefore, RBD is a core determinant for tissue tropism and host range of CoVs. This article presents SARS-CoV-2 phylogenetic trees, comparison and analysis of genome, spike protein, and RBD amino acid sequences of different CoVs, deducing source and etiology of COVID-19 and evolutionary relationship among SARS-CoV-2 in human. The S-protein amino acid sequence identity between SARS-CoV-2 and related beta-CoVs showed that bat/Yunnan/RaTG13 shares highest similarity of 97.43%. abstract: The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability. url: https://doi.org/10.1101/2020.03.16.993816 doi: 10.1101/2020.03.16.993816 id: cord-262145-i29e3fge author: Huang, Kuan-Ying A. title: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans date: 2020-10-19 words: 2949.0 sentences: 207.0 pages: flesch: 61.0 cache: ./cache/cord-262145-i29e3fge.txt txt: ./txt/cord-262145-i29e3fge.txt summary: A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. The MAbs with 161 strong anti-RBD binding have a relatively long heavy chain CDR3 length (50% 162 binding concentration <0.5 µg/ml versus >0.5 µg/ml, p=0.03, two-tailed Mann-163 Whitney test; Supplemental Figure 3 The 32 anti-spike glycoprotein MAbs were systematically examined by plaque 173 reduction neutralisation (PRNT) assay for neutralisation of wild type SARS-CoV-2 174 virus (see methods; summarised in Table 1 ). Potent neutralising antibodies to the RBD of SARS-CoV-2 spike glycoprotein were 188 identified and we thus analyse the blockade of the ACE2-RBD interaction by anti-189 RBD antibodies in two assays ( Figure 3 , Table 1 The structure of VHH72-Fc bound to RBD is known (17) and its footprint on the 198 RBD does not overlap that of ACE2, so inhibition is thought to occur by steric 199 hindrance. abstract: Serological and plasmablast responses and plasmablast-derived IgG monoclonal antibodies (MAbs) have been analysed in three COVID-19 patients with different clinical severities. Potent humoral responses were detected within 3 weeks of onset of illness in all patients and the serological titre was elicited soon after or concomitantly with peripheral plasmablast response. An average of 13.7% and 13.0% of plasmablast-derived MAbs were reactive with virus spike glycoprotein or nucleocapsid, respectively. A subset of anti-spike (10 of 32) and over half of anti-nucleocapsid (19 of 35) antibodies cross-reacted with other betacoronaviruses tested and harboured extensive somatic mutations, indicative of an expansion of memory B cells upon SARS-CoV-2 infection. Fourteen of 32 anti-spike MAbs, including five anti-RBD, three anti-non-RBD S1 and six anti-S2, neutralised wild-type SARS-CoV-2 in independent assays. Anti-RBD MAbs were further grouped into four cross-inhibiting clusters, of which six antibodies from three separate clusters blocked the binding of RBD to ACE2 and five were neutralising. All ACE2-blocking anti-RBD antibodies were isolated from two patients with prolonged fever, which is compatible with substantial ACE2-blocking response in their sera. At last, the identification of non-competing pairs of neutralising antibodies would offer potential templates for the development of prophylactic and therapeutic agents against SARS-CoV-2. url: https://doi.org/10.1101/2020.08.28.267526 doi: 10.1101/2020.08.28.267526 id: cord-256572-sqz8yc7b author: Huo, Jiandong title: Neutralization of SARS-CoV-2 by destruction of the prefusion Spike date: 2020-05-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: There are as yet no licenced therapeutics for the COVID-19 pandemic. The causal coronavirus (SARS-CoV-2) binds host cells via a trimeric Spike whose receptor binding domain (RBD) recognizes angiotensin-converting enzyme 2 (ACE2), initiating conformational changes that drive membrane fusion. We find that monoclonal antibody CR3022 binds the RBD tightly, neutralising SARS-CoV-2 and report the crystal structure at 2.4 Å of the Fab/RBD complex. Some crystals are suitable for screening for entry-blocking inhibitors. The highly conserved, structure-stabilising, CR3022 epitope is inaccessible in the prefusion Spike, suggesting that CR3022 binding would facilitate conversion to the fusion-incompetent post-fusion state. Cryo-EM analysis confirms that incubation of Spike with CR3022 Fab leads to destruction of the prefusion trimer. Presentation of this cryptic epitope in an RBD-based vaccine might advantageously focus immune responses. Binders at this epitope may be useful therapeutically, possibly in synergy with an antibody blocking receptor attachment. Highlights CR3022 neutralises SARS-CoV-2 Neutralisation is by destroying the prefusion SPIKE conformation This antibody may have therapeutic potential alone or with one blocking receptor attachment url: https://doi.org/10.1101/2020.05.05.079202 doi: 10.1101/2020.05.05.079202 id: cord-103204-gt6upfri author: Hölzer, Martin title: PoSeiDon: a Nextflow pipeline for the detection of evolutionary recombination events and positive selection date: 2020-05-20 words: 1791.0 sentences: 108.0 pages: flesch: 42.0 cache: ./cache/cord-103204-gt6upfri.txt txt: ./txt/cord-103204-gt6upfri.txt summary: Summary PoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. A comprehensive evolutionary analysis of significantly positively selected sites consist of several complicated steps, including (1) in-frame alignment; (2) Indel correction; (3) phylogenetic tree calculation; (4) selection of a best-fitting nucleotide substitution * To whom correspondence should be addressed. model; (5) detection of topological incongruence and breakpoint selection to describe putative recombination events; (6) calculation of positively selected sites (ω > 1) under varying models; (7) and their impact on the selective pressure acting on the whole alignment. PoSeiDon comprises an assembly of different scripts and tools ( Fig. 1) that allow for the detection of recombination and positive selection in protein-coding sequences. Here we present PoSeiDon, an easy-to-use Nextflow pipeline for the accurate detection of site-specific positive selection and recombination events in protein-coding sequences. abstract: Summary PoSeiDon is an easy-to-use pipeline that helps researchers to find recombination events and sites under positive selection in protein-coding sequences. By entering homologous sequences, PoSeiDon builds an alignment, estimates a best-fitting substitution model, and performs a recombination analysis followed by the construction of all corresponding phylogenies. Finally, significantly positive selected sites are detected according to different models for the full alignment and possible recombination fragments. The results of PoSeiDon are summarized in a user-friendly HTML page providing all intermediate results and the graphical representation of recombination events and positively selected sites. Availability and implementation PoSeiDon is freely available at https://github.com/hoelzer/poseidon. The pipeline is implemented in Nextflow with Docker support and processes the output of various tools. Contact hoelzer.martin@gmail.com url: https://doi.org/10.1101/2020.05.18.102731 doi: 10.1101/2020.05.18.102731 id: cord-103568-zesg4atp author: Iacullo, Carly title: Non-selective inhibition of the motor system following unexpected and expected infrequent events date: 2020-03-26 words: 5559.0 sentences: 272.0 pages: flesch: 44.0 cache: ./cache/cord-103568-zesg4atp.txt txt: ./txt/cord-103568-zesg4atp.txt summary: Consequently, in line with the proposal that unexpected sensory events lead to an automatic recruitment of the brain''s reactive inhibition circuity even when stopping is not explicitly required (i.e., in the absence of proactive control), such events do indeed also produce non-selective suppression of CSE (Wessel & Aron, 2013) . Therefore, the goal of the current study was to investigate whether expected infrequent events can produce reactive motor inhibition, as indexed by non-selective CSE suppression. Using single-pulse TMS combined with EMG of task-unrelated hand muscles while participants performed forced-choice reaction time tasks with their feet, we found that infrequent expected sounds are indeed followed by a non-selective suppression of task-unrelated motor effectors. The latter finding replicates our previous report of non-selective CSE suppression in a verbal reaction time task when unexpected sounds were presented prior to the imperative stimulus (Wessel & Aron, 2013) . abstract: Motor inhibition is a key control mechanism that allows humans to rapidly adapt their actions in response to environmental events. One of the hallmark signatures of rapidly exerted, reactive motor inhibition is the non-selective suppression of cortico-spinal excitability (CSE): unexpected sensory stimuli lead to a suppression of CSE across the entire motor system, even in muscles that are inactive. Theories suggest that this reflects a fast, automatic, and broad engagement of inhibitory control, which facilitates behavioral adaptations to unexpected changes in the sensory environment. However, it is an open question whether such non-selective CSE suppression is truly due to the unexpected nature of the sensory event, or whether it is sufficient for an event to be merely infrequent (but not unexpected). Here, we report data from two experiments in which human subjects experienced both unexpected and expected infrequent events during a simple reaction time task while CSE was measured from a task-unrelated muscle. We found that expected infrequent events can indeed produce non-selective CSE suppression – but only when they occur during movement initiation. In contrast, unexpected infrequent events produce non-selective CSE suppression even in the absence of movement initiation. Moreover, CSE suppression due to unexpected events occurs at shorter latencies compared to expected infrequent events. These findings demonstrate that unexpectedness and stimulus infrequency have qualitatively different suppressive effects on the motor system. They also have key implications for studies that seek to disentangle neural and psychological processes related to motor inhibition and stimulus detection. url: https://doi.org/10.1101/2020.03.25.008789 doi: 10.1101/2020.03.25.008789 id: cord-320490-3jmo35jc author: Ismail, Saba title: Immuno-informatics Characterization SARS-CoV-2 Spike Glycoprotein for Prioritization of Epitope based Multivalent Peptide Vaccine date: 2020-04-12 words: 6688.0 sentences: 412.0 pages: flesch: 52.0 cache: ./cache/cord-320490-3jmo35jc.txt txt: ./txt/cord-320490-3jmo35jc.txt summary: In this study, we characterized the SARS-CoV-2 spike glycoprotein by immune-informatics techniques to put forward potential B and T cell epitopes, followed by the use of epitopes in construction of a multi-epitope peptide vaccine construct (MEPVC). Stable conformation of the MEPVC with a representative innate immune TLR3 receptor was observed involving strong hydrophobic and hydrophilic chemical interactions, along with enhanced contribution from salt-bridges towards inter-molecular stability. The study presented, herein, is an attempt to get insights about antigenic determinants of SARS-CoV-2 spike glycoprotein and highlight all antigenic epitopes [31] of the spike that can be used specifically for the design of a multi-epitope peptide vaccine construct (MEPVC) [32] to counter COVID-19 infections. The epitopes predicted by immunoinformatics techniques were fused together as well as to β-defensin adjuvant [33, 34] to boost the antibody production and longThe MEPVC affinity for an appropriate immune receptor as an agonist was checked in the step of molecular docking [60] . abstract: The COVID-19 pandemic caused by SARS-CoV-2 is a public-health emergency of international concern and thus calling for the development of safe and effective therapeutics and prophylactics particularly a vaccine to protect against the infection. SARS-CoV-2 spike glycoprotein is an attractive candidate for vaccine, antibodies and inhibitor development because of many roles it plays in attachment, fusion and entry into the host cell. In this study, we characterized the SARS-CoV-2 spike glycoprotein by immune-informatics techniques to put forward potential B and T cell epitopes, followed by the use of epitopes in construction of a multi-epitope peptide vaccine construct (MEPVC). The MEPVC revealed robust host immune system simulation with high production of immunoglobulins, cytokines and interleukins. Stable conformation of the MEPVC with a representative innate immune TLR3 receptor was observed involving strong hydrophobic and hydrophilic chemical interactions, along with enhanced contribution from salt-bridges towards inter-molecular stability. Molecular dynamics simulation in solution aided further in interpreting strong affinity of the MEPVC for TLR3. This stability is the attribute of several vital residues from both TLR3 and MEPVC as shown by radial distribution function (RDF) and a novel analytical tool axial frequency distribution (AFD). Comprehensive binding free energies estimation was provided at the end that concluded major domination by electrostatic and minor from van der Waals. Summing all, the designed MEPVC has tremendous potential of providing protective immunity against COVID-19 and thus has the potential to be considered in experimental studies. url: https://doi.org/10.1101/2020.04.05.026005 doi: 10.1101/2020.04.05.026005 id: cord-332374-cbiw6yvb author: Israeli, Ofir title: Evaluating the efficacy of RT-qPCR SARS-CoV-2 direct approaches in comparison to RNA extraction date: 2020-06-10 words: 1051.0 sentences: 77.0 pages: flesch: 55.0 cache: ./cache/cord-332374-cbiw6yvb.txt txt: ./txt/cord-332374-cbiw6yvb.txt summary: Very recently, two studies [6] [7] used a direct no-buffer RT-qPCR approach which identified > 90% of the tested clinical samples. In this study, we tested the diagnostic efficiency following thermal inactivation (65°C for 30min and 95°C for 10min) without addition of lysis buffers ("no buffer") or following lysis by three buffers (Virotype, QuickExtract and 2% Triton-X-100) and compared it to diagnosis after standard RNA extraction. Samples included buffers spiked with SARS-CoV-2, at concentrations 0.1-100,000 PFU/ml and 30 clinical samples, previously diagnosed as positive (20) and negative (10). The limit of detection was 1 PFU/ml: In this concentration samples in the no buffer mode and Virotype at 95°C were not detected, while the RNA extraction mode averaged the lowest critical threshold ( Ct=29.8) followed by QuickExtract and Triton. SARS-CoV-2 detection by direct rRT-PCR without RNA extraction. Direct RT-qPCR detection of SARS-CoV-2 RNA from patient nasopharyngeal swabs without an RNA extraction step abstract: SARS-CoV-2 genetic identification is based on viral RNA extraction prior to RT-qPCR assay, however recent studies support the elimination of the extraction step. Herein, we assessed the RNA extraction necessity, by comparing RT-qPCR efficacy in several direct approaches vs. the gold standard RNA extraction, in detection of SARS-CoV-2 from laboratory samples as well as clinical Oro-nasopharyngeal SARS-CoV-2 swabs. Our findings show advantage for the extraction procedure, however a direct no-buffer approach might be an alternative, since it identified up to 70% of positive clinical specimens. url: https://doi.org/10.1101/2020.06.10.144196 doi: 10.1101/2020.06.10.144196 id: cord-256607-wpywh8c9 author: Itokawa, Kentaro title: Disentangling primer interactions improves SARS-CoV-2 genome sequencing by the ARTIC Network’s multiplex PCR date: 2020-06-01 words: 1415.0 sentences: 76.0 pages: flesch: 59.0 cache: ./cache/cord-256607-wpywh8c9.txt txt: ./txt/cord-256607-wpywh8c9.txt summary: The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network''s original (V1) and modified (V3) primer set. Alongside with this modification, the ARTIC Network itself released another 108 modified version of primer set known as V3 in 24 th March 2020 (Loman and Quick 2020) after replacement for the same clinical sample (previously deposited to GISAID with ID EPI_ISL_416596, Ct=28.5, 1/25 input per reaction). Fig 3 Abundance of 98 amplicons at 8 different annealing/extension temperatures with the three different primer sets on a same clinical sample (previously deposited to GISAID with ID EPI_ISL_416584, Ct=16, 1/300 input per reaction). The orange lines and points indicate the abundances of amplicons whose primers were not modified but predicted to be eliminated the adverse primer interactions in the N1 primer set. abstract: Since December 2019, the coronavirus disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2 has rapidly spread to almost every nation in the world. Soon after the pandemic was recognized by epidemiologists, a group of biologists comprising the ARTIC Network, has devised a multiplexed polymerase chain reaction (PCR) protocol and primer set for targeted whole-genome amplification of SARS-CoV-2. The ARTIC primer set amplifies 98 amplicons, which are separated only in two PCRs, across a nearly entire viral genome. The original primer set and protocol showed a fairly small amplification bias when clinical samples with relatively high viral loads were used. However, when sample’s viral load was low, several amplicons, especially amplicons 18 and 76, exhibited low coverage or complete dropout. We have determined that these dropouts were due to a dimer formation between the forward primer for amplicon 18, 18_LEFT, and the reverse primer for amplicon 76, 76_RIGHT. Replacement of 76_RIGHT with an alternatively designed primer was sufficient to produce a drastic improvement in coverage of both amplicons. Based on this result, we replaced 12 primers in total in the ARTIC primer set that were predicted to be involved in 14 primer interactions. The resulting primer set, version N1 (NIID-1), exhibits improved overall coverage compared to the ARTIC Network’s original (V1) and modified (V3) primer set. url: https://doi.org/10.1101/2020.03.10.985150 doi: 10.1101/2020.03.10.985150 id: cord-104035-ykyr2gvl author: Ivanov, Mark V. title: Boosting the MS1-only proteomics with machine learning allows 2000 protein identifications in 5-minute proteome analysis date: 2020-10-29 words: 1844.0 sentences: 115.0 pages: flesch: 43.0 cache: ./cache/cord-104035-ykyr2gvl.txt txt: ./txt/cord-104035-ykyr2gvl.txt summary: A number of methods and approaches to MS/MS-free proteome analysis have been proposed and widely explored starting from the early Accurate Mass and Tag (Time) method [21] [22] [23] [24] [25] to a recent truly (e.g., without employing tandem mass spectrometry at any step in the workflow) MS/MS-free realizations 26, 27 . 27 Because the method does not employ isolation and fragmentation steps, the time for peptide separation can be reduced significantly to few minutes and the number of MS1 spectra available for processing will only be limited by the acquisition rate of the mass analyzer operating at high mass resolution. Also, the method was upgraded and tested for processing MS1-only data obtained using high resolution mass spectrometry and the high-field asymmetric waveform ion mobility, FAIMS 35 , which was found increasingly applicable in proteomic research 36, 37 as it provides additional separation dimension for peptides at the front end of a mass spectrometer. abstract: Proteome-wide analyses most often rely on tandem mass spectrometry imposing considerable instrumental time consumption that is one of the main obstacles in a broader acceptance of proteomics in biomedical and clinical research. Recently, we presented a fast proteomic method termed DirectMS1 based on MS1-only mass spectra acquisition and data processing. The method allowed significant squeezing of the proteome-wide analysis to a few minute time frame at the depth of quantitative proteome coverage of 1000 proteins at 1% FDR. In this work, to further increase the capabilities of the DirectMS1 method, we explored the opportunities presented by the recent progress in the machine learning area and applied the LightGBM tree-based learning algorithm into the scoring of peptide-feature matches when processing MS1 spectra. Further, we integrated the peptide feature identification algorithm of DirectMS1 with the recently introduced peptide retention time prediction utility, DeepLC. Additional approaches to improve performance of the DirectMS1 method are discussed and demonstrated, such as FAIMS coupled to the Orbitrap mass analyzer. As a result of all improvements to DirectMS1, we succeeded in identifying more than 2000 proteins at 1% FDR from the HeLa cell line in a 5 minute LC-MS1 analysis. url: https://doi.org/10.1101/2020.10.29.359075 doi: 10.1101/2020.10.29.359075 id: cord-350821-0qfoc553 author: Jahromi, Reza title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 date: 2020-06-01 words: 1941.0 sentences: 113.0 pages: flesch: 46.0 cache: ./cache/cord-350821-0qfoc553.txt txt: ./txt/cord-350821-0qfoc553.txt summary: title: Synergistic effects of anionic surfactants on coronavirus (SARS-CoV-2) virucidal efficiency of sanitizing fluids to fight COVID-19 In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Twelve sanitizing fluids with different recipes, as shown in Table 1 , were prepared to examine the effect of individual components and mixtures on evaporation rate and SARS-CoV-2 virucidal efficiency of the solutions. Furthermore, the addition of 3% dish soap to the ethanol solution (S1) increased the evaporation time by about 63% from 24 to 39 s (of fluid S9), as shown in Figure 2 . abstract: Our surrounding environment, especially often-touched contaminated surfaces, plays an important role in the transmission of pathogens in society. The shortage of effective sanitizing fluids, however, became a global challenge quickly after the coronavirus disease-19 (COVID-19) outbreak in December 2019. In this study, we present the effect of surfactants on coronavirus (SARS-CoV-2) virucidal efficiency in sanitizing fluids. Sodium dodecylbenzenesulfonate (SDBS), sodium laureth sulfate (SLS), and two commercial dish soap and liquid hand soap were studied with the goal of evaporation rate reduction in sanitizing liquids to maximize surface contact time. Twelve fluids with different recipes composed of ethanol, isopropanol, SDBS, SLS, glycerin, and water of standardized hardness (WSH) were tested for their evaporation time and virucidal efficiency. Evaporation time increased by 17-63% when surfactant agents were added to the liquid. In addition, surfactant incorporation enhanced the virucidal efficiency between 15-27% according to the 4-field test in the EN 16615:2015 European Standard method. Most importantly, however, we found that surfactant addition provides a synergistic effect with alcohols to inactivate the SARS-CoV-2 virus. This study provides a simple, yet effective solution to improve the virucidal efficiency of commonly used sanitizers. url: https://doi.org/10.1101/2020.05.29.124107 doi: 10.1101/2020.05.29.124107 id: cord-303069-ss6g3jkg author: Jakhar, Renu title: An Immunoinformatics Study to Predict Epitopes in the Envelope Protein of SARS-COV-2 date: 2020-05-26 words: 3379.0 sentences: 202.0 pages: flesch: 52.0 cache: ./cache/cord-303069-ss6g3jkg.txt txt: ./txt/cord-303069-ss6g3jkg.txt summary: A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. The aim of this study is to analyze envelope protein strains using in silico approaches looking for the conservancy, which is further studied to predict all potential epitopes that can be used after in vitro and in vivo confirmation as a therapeutic peptide vaccine [22, 23, 24] . Envelope protein from the SARS-CoV-2 was analyzed using the IEDB MHC-1 binding prediction tool to predict the T cell epitope suggested interacting with different types of MHC Class I alleles. Analysis of the genome sequence and prediction of B-cell epitopes of the envelope protein of Middle East respiratory syndrome-coronavirus abstract: COVID-19 is a new viral emergent human disease caused by a novel strain of Coronavirus. This virus has caused a huge problem in the world as millions of the people are affected with this disease in the entire world. We aimed to design a peptide vaccine for COVID-19 particularly for the envelope protein using computational methods to predict epitopes inducing the immune system and can be used later to create a new peptide vaccine that could replace conventional vaccines. A total of available 370 sequences of SARS-CoV-2 were retrieved from NCBI for bioinformatics analysis using Immune Epitope Data Base (IEDB) to predict B and T cells epitopes. Then we docked the best predicted CTL epitopes with HLA alleles. CTL cell epitopes namely interacted with MHC class I alleles and we suggested them to become universal peptides based vaccine against COVID-19. Potentially continuous B cell epitopes were predicted using tools from IEDB. The Allergenicity of predicted epitopes was analyzed by AllerTOP tool and the coverage was determined throughout the worlds. We found these CTL epitopes to be T helper epitopes also. The B cell epitope, SRVKNL and T cell epitope, FLAFVVFLL were suggested to become a universal candidate for peptide-based vaccine against COVID-19. We hope to confirm our findings by adding complementary steps of both in vitro and in vivo studies to support this new universal predicted candidate. url: https://doi.org/10.1101/2020.05.26.115790 doi: 10.1101/2020.05.26.115790 id: cord-103081-k7ev5qkn author: Janosevic, Danielle title: The orchestrated cellular and molecular responses of the kidney to endotoxin define the sepsis timeline date: 2020-05-30 words: 4505.0 sentences: 310.0 pages: flesch: 57.0 cache: ./cache/cord-103081-k7ev5qkn.txt txt: ./txt/cord-103081-k7ev5qkn.txt summary: Note that the expression of cluster-defining markers varied significantly during the injury and 63 recovery phases of sepsis ( Fig. S1b; Supplementary Table 1 ). One of the subclusters showed 112 increased expression of alternatively activated macrophages (M2) markers such as Arg1 113 (Arginase 1) and Mrc1 (Cd206) 27 at later time points (36 hours, Supplementary Fig. 4b) . Such 181 communication patterns among these four cell types may also explain macrophage clustering 182 around S1 tubules at later time points in sepsis as we previously reported 13 . To this end, we selected the differentially expressed genes from all cells combined (pseudo 203 bulk) for each time point across the mouse sepsis timeline (Supplementary Table 4) . Our data 215 cover nearly all renal cell types and are time-anchored, thus providing a detailed and precise 216 view of the evolution of sepsis in the kidney at the cellular and molecular level. abstract: Clinical sepsis is a highly dynamic state that progresses at variable rates and has life-threatening consequences. Staging patients along the sepsis timeline requires a thorough knowledge of the evolution of cellular and molecular events at the tissue level. Here, we investigated the kidney, an organ central to the pathophysiology of sepsis. Single cell RNA sequencing revealed the involvement of various cell populations in injury and repair to be temporally organized and highly orchestrated. We identified key changes in gene expression that altered cellular functions and can explain features of clinical sepsis. These changes converged towards a remarkable global cell-cell communication failure and organ shutdown at a well-defined point in the sepsis timeline. Importantly, this time point was also a transition towards the emergence of recovery pathways. This rigorous spatial and temporal definition of murine sepsis will uncover precise biomarkers and targets that can help stage and treat human sepsis. url: https://doi.org/10.1101/2020.05.27.118620 doi: 10.1101/2020.05.27.118620 id: cord-307242-e20gtx0z author: Jegouic, Sophie M. title: Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping date: 2020-05-22 words: 3454.0 sentences: 177.0 pages: flesch: 52.0 cache: ./cache/cord-307242-e20gtx0z.txt txt: ./txt/cord-307242-e20gtx0z.txt summary: Similar western blot analysis of total protein extracts following induction of logarithmic phase E.coli cultures with IPTG confirmed the expression of His-tagged S antigen of the predicted molecular weight in all cases ( Figure 3 , upper panel). Nevertheless, we found that S protein fragments prepared for gel electrophoresis using non-reducing loading buffer could be used successfully for epitope mapping of 2 S reactive monoclonal antibodies, 3G9, an unpublished mouse mAb generated to SARS S, and CR3022, a human mAb also isolated originally to SARS [19] but shown to cross-react with SARS-CoV-2. To provide an additional level of validation and to add epitope specificity to the data, 2 of the sera scoring positive by S1 ELISA were used as probes on western blots using full length S expressed in insect cells (cf. Optimization of the Production Process and Characterization of the Yeast-Expressed SARS-CoV Recombinant Receptor-Binding Domain ( RBD219-N1 ), a SARS Vaccine Candidate abstract: The newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes. url: https://doi.org/10.1101/2020.05.21.109298 doi: 10.1101/2020.05.21.109298 id: cord-270257-5f95gve3 author: Jeon, Sangeun title: Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs date: 2020-03-28 words: 1145.0 sentences: 79.0 pages: flesch: 53.0 cache: ./cache/cord-270257-5f95gve3.txt txt: ./txt/cord-270257-5f95gve3.txt summary: Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19. We screened approximately 3,000 FDA-and IND-approved drug library against SARS-CoV to identify antiviral drug candidates (manuscript in preparation). Among the 48 drugs that were evaluated in our study, 24 drugs showed potential antiviral activities against SARS-CoV-2 with IC 50 values in Second, ciclesonide is another interesting drug candidate for further development although its antiviral potency was much lower (IC 50 = 4.33 µM) than niclosamide. Prior to our evaluation of 48 drugs against SARS-CoV-2 infection, we also tested antiviral activity of several other drugs based on the cytopathic effect of the virus in the presence of each drug ( Figure 2 ). abstract: COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19. url: https://doi.org/10.1101/2020.03.20.999730 doi: 10.1101/2020.03.20.999730 id: cord-353777-t8q99tlq author: Jia, Yong title: Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity date: 2020-04-11 words: 3217.0 sentences: 180.0 pages: flesch: 58.0 cache: ./cache/cord-353777-t8q99tlq.txt txt: ./txt/cord-353777-t8q99tlq.txt summary: The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. The discrepant phylogenies for the spike protein and its 23 receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARSDespite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that 25 leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27 th January 2020 from 26 abstract: Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020. url: https://doi.org/10.1101/2020.04.09.034942 doi: 10.1101/2020.04.09.034942 id: cord-297044-tpp40j0g author: Jin, Zhenming title: Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur date: 2020-04-28 words: 1146.0 sentences: 84.0 pages: flesch: 62.0 cache: ./cache/cord-297044-tpp40j0g.txt txt: ./txt/cord-297044-tpp40j0g.txt summary: title: Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug Carmofur The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease 24 (M pro ). Here the X-ray crystal structure of M pro in complex with Carmofur reveals that 25 the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, 26 whereas its fatty acid tail occupies the hydrophobic S2 subsite. Here, we present the 1.6 Å X-ray crystal structure of SARS-CoV-2 M pro in complex 49 with Carmofur (Fig. 1b, domain II feature the catalytic dyad residues Cys145 and His41 (Fig. 1c, d) . Here we determined the inhibitory 94 effect of Carmofur against SARS-CoV-2 infection on Vero E6 cells, as previously 95 described 20 (Fig. 2) . abstract: The antineoplastic drug Carmofur was shown to inhibit SARS-CoV-2 main protease (Mpro). Here the X-ray crystal structure of Mpro in complex with Carmofur reveals that the carbonyl reactive group of Carmofur is covalently bound to catalytic Cys145, whereas its fatty acid tail occupies the hydrophobic S2 subsite. Carmofur inhibits viral replication in cells (EC50 = 24.30 μM) and it is a promising lead compound to develop new antiviral treatment for COVID-19. url: https://doi.org/10.1101/2020.04.09.033233 doi: 10.1101/2020.04.09.033233 id: cord-103249-k35o3gxe author: Johannsen, Leif title: Robotic light touch assists human balance control during maximum forward reaching date: 2019-11-20 words: 3082.0 sentences: 154.0 pages: flesch: 51.0 cache: ./cache/cord-103249-k35o3gxe.txt txt: ./txt/cord-103249-k35o3gxe.txt summary: We speculated, therefore, that minimization of the interaction 106 forces and their variability at the contact location during IPT acts as an implicit task constraint and shared goal In the present study, we intended to contrast the effects of human IPT (hIPT) on CR''s postural performance 112 against the effects of two different modes of robotic IPT (rIPT) and expected specific costs and benefits on body 113 sway and postural performance due to the robotic response modes. As the coupling 116 between two humans with IPT in terms of the interaction forces is intrinsically more noisy due to each 117 individual''s motion dynamics and response delays, we expected that a predictive mode of the robotic system 118 would result in a less noisy haptic coupling and therefore enhance performance in the MFR task, such as greater 119 reaching distance with less body sway. abstract: Objective We investigated how light interpersonal touch (IPT) provided by a robotic system supports human individuals performing a challenging balance task compared to IPT provided by a human partner. Background IPT augments the control of body balance in contact receivers without a provision of mechanical body weight support. The nature of the processes governing the social haptic interaction, whether they are predominantly reactive or predictive, is uncertain. Method Ten healthy adult individuals performed maximum forward reaching (MFR) without visual feedback while standing upright. We evaluated their control of reaching behaviour and of body balance during IPT provided by either another human individual or by a robotic system in two alternative control modes (reactive vs predictive). Results Changes in reaching behaviour under the robotic IPT, such as lower speed and straighter direction were linked to reduced body sway. MFR of the contact receiver was influenced by the robotic control mode such as that a predictive mode reduced movement variability and increased postural stability to a greater extend in comparison to human IPT. The effects of the reactive robotic system, however, more closely resembled the effects of IPT provided by human contact provider. Conclusion The robotic IPT system was as supportive as human IPT. Robotic IPT seemed to afford more specific adjustments, such as trading reduced speed for increased accuracy, to meet the intrinsic demands and constraints of the robotic system. Possibly, IPT provided by a human contact provider reflected reactive interpersonal postural coordination more similar to the robotic system’s follower mode. Précis Interpersonal touch support by a robotic system was evaluated against support provided a human partner during maximum forward reaching. Human contact receivers showed comparable benefits in their reaching postural performance between the support conditions. Coordination with the robotic system, nevertheless, afforded specific adaptations in the reaching behaviour. url: https://doi.org/10.1101/848432 doi: 10.1101/848432 id: cord-258650-aeyf0yu1 author: Joshi, Bhrugesh title: deepMINE - Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 date: 2020-04-02 words: 1995.0 sentences: 98.0 pages: flesch: 52.0 cache: ./cache/cord-258650-aeyf0yu1.txt txt: ./txt/cord-258650-aeyf0yu1.txt summary: title: deepMINE Natural Language Processing based Automatic Literature Mining and Research Summarization for Early-Stage Comprehension in Pandemic Situations specifically for COVID-19 In the demanding situation of COVID-19, we applied the literature mining with user entered keyword(s) and automatic generation of brief summary of research articles, that user searches for. The deepMINE is primarily performing two major functions namely mining of articles from available open data sources using user-entered keywords and generate brief technical summary in natural language for a quick review of articles that user interested with. The system has used the deep natural language processing-based text summarization for generating detailed technical summary given the research article as an input. Our system deepMINE is providing mining from 29,315 research articles with keywords by scanning nearly 1,46,115,136 English words available in literature dataset in not greater than 1.5 seconds. abstract: The recent pandemic created due to Novel Coronavirus (nCOV-2019) from Wuhan, China demanding a large scale of a general health emergency. This demands novel research on the vaccine to fight against this pandemic situation, re-purposing of the existing drugs, phylogenetic analysis to identify the origin and determine the similarity with other known viruses, etc. The very preliminary task from the research community is to analyze the wide verities of existing related research articles, which is very much time-consuming in such situations where each minute counts for saving hundreds of human lives. The entire manual processing is even lower down the efficiency in mining the information. We have developed a complete automatic literature mining system that delivers efficient and fast mining from existing biomedical literature databases. With the help of modern-day deep learning algorithms, our system also delivers a summarization of important research articles that provides ease and fast comprehension of critical research articles. The system is currently scanning nearly 1,46,115,136 English words from 29,315 research articles in not greater than 1.5 seconds with multiple search keywords. Our research article presents the criticality of literature mining, especially in pandemic situations with the implementation and online deployment of the system. url: https://doi.org/10.1101/2020.03.30.014555 doi: 10.1101/2020.03.30.014555 id: cord-324251-wgtatr8v author: Joshi, Madhvi title: Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology date: 2020-07-13 words: 608.0 sentences: 46.0 pages: flesch: 57.0 cache: ./cache/cord-324251-wgtatr8v.txt txt: ./txt/cord-324251-wgtatr8v.txt summary: title: Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology Latest edition to this pandemic list is COVID-19, caused by the novel coronavirus, SARS-CoV-2. Here, 361 SARS-CoV-2 genomes from across Gujarat have been sequenced and analyzed in order to understand its phylogenetic distribution and variants against global and national sequences. Further, variants were analyzed from diseased and recovered patients from Gujarat and the World to understand its role in pathogenesis. From missense mutations, found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in nucleocapsid (N) gene was found to be significantly associated with mortality in patients. SARS-CoV-2 genomes from Gujarat are forming distinct cluster under GH clade of GISAID. Positive selection of ORF3a and 477 ORF8 genes drives the evolution of SARS-CoV-2 during the 2020 COVID-19 pandemic Full-genome sequences of the first two SARS-CoV-2 485 viruses from India abstract: Humanity has seen numerous pandemics during its course of evolution. The list includes many such as measles, Ebola, SARS, MERS, etc. Latest edition to this pandemic list is COVID-19, caused by the novel coronavirus, SARS-CoV-2. As of 4th July 2020, COVID-19 has affected over 10 million people from 170+ countries, and 5,28,364 deaths. Genomic technologies have enabled us to understand the genomic constitution of the pathogens, their virulence, evolution, rate of mutations, etc. To date, more than 60,000 virus genomes have been deposited in the public depositories like GISAID and NCBI. While we are writing this, India is the 3rd most-affected country with COVID-19 with 0.6 million cases, and >18000 deaths. Gujarat is the fourth highest affected state with 5.44 percent death rate compared to national average of 2.8 percent. Here, 361 SARS-CoV-2 genomes from across Gujarat have been sequenced and analyzed in order to understand its phylogenetic distribution and variants against global and national sequences. Further, variants were analyzed from diseased and recovered patients from Gujarat and the World to understand its role in pathogenesis. From missense mutations, found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in nucleocapsid (N) gene was found to be significantly associated with mortality in patients. The other significant deleterious variant found in diseased patients from Gujarat and the world is G25563T, which is located in Orf3a and has a potential role in viral pathogenesis. SARS-CoV-2 genomes from Gujarat are forming distinct cluster under GH clade of GISAID. url: https://doi.org/10.1101/2020.07.10.197095 doi: 10.1101/2020.07.10.197095 id: cord-103213-oinumv1z author: Kalantar, Katrina L. title: IDseq – An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring date: 2020-04-18 words: 10494.0 sentences: 562.0 pages: flesch: 46.0 cache: ./cache/cord-103213-oinumv1z.txt txt: ./txt/cord-103213-oinumv1z.txt summary: The IDseq Portal accepts raw mNGS data, performs host and quality filtration steps, then executes an assembly-based alignment pipeline which results in the assignment of reads and contigs to taxonomic categories. First, relevant QC metrics and pipeline run information, including the number of reads remaining at each step of the host and quality filtering steps as well as estimates of internal control abundances are provided for each sample (Figure 2AB, Methods) . The idseq-bench tool was used to generate 17 simulated NGS samples from Rhinovirus C genomes at varying levels of divergence (after in-silico forward evolution from a reference sequence obtained from the NCBI database), ranging from 100% identical to the reference sequence to 25% similar (at the nucleotide level) (Methods, Figure 4A , Table S3 ). abstract: Background Metagenomic next generation sequencing (mNGS) has enabled the rapid, unbiased detection and identification of microbes without pathogen-specific reagents, culturing, or a priori knowledge of the microbial landscape. mNGS data analysis requires a series of computationally intensive processing steps to accurately determine the microbial composition of a sample. Existing mNGS data analysis tools typically require bioinformatics expertise and access to local server-class hardware resources. For many research laboratories, this presents an obstacle, especially in resource limited environments. Findings We present IDseq, an open source cloud-based metagenomics pipeline and service for global pathogen detection and monitoring (https://idseq.net). The IDseq Portal accepts raw mNGS data, performs host and quality filtration steps, then executes an assembly-based alignment pipeline which results in the assignment of reads and contigs to taxonomic categories. The taxonomic relative abundances are reported and visualized in an easy-to-use web application to facilitate data interpretation and hypothesis generation. Furthermore, IDseq supports environmental background model generation and automatic internal spike-in control recognition, providing statistics which are critical for data interpretation. IDseq was designed with the specific intent of detecting novel pathogens. Here, we benchmark novel virus detection capability using both synthetically evolved viral sequences, and real-world samples, including IDseq analysis of a nasopharyngeal swab sample acquired and processed locally in Cambodia from a tourist from Wuhan, China, infected with the recently emergent SARS-CoV-2. Conclusion The IDseq Portal reduces the barrier to entry for mNGS data analysis and enables bench scientists, clinicians, and bioinformaticians to gain insight from mNGS datasets for both known and novel pathogens. url: https://doi.org/10.1101/2020.04.07.030551 doi: 10.1101/2020.04.07.030551 id: cord-103674-pmbpx162 author: Kalaycı, Salih title: The Linkage among Sea Transportation, Trade Liberalization and Industrial Development in the context of Carbon Dioxide Emissions: An Empirical Investigation from China date: 2020-07-13 words: 4523.0 sentences: 226.0 pages: flesch: 45.0 cache: ./cache/cord-103674-pmbpx162.txt txt: ./txt/cord-103674-pmbpx162.txt summary: According to results of FMOLS, DOLS and CCR models there is a long-term stable relationship between sea transportation, trade liberalization, industrial development and carbon dioxide emissions which is proved empirically. In this study, empirical results proved the impact of sea transportation, trade liberalization and industrial development on carbon dioxide emissions for China from 1980 to 2013. The long-run relationship between carbon dioxide emissions 2 sea transportation trade liberalization and industrial development is investigated through f bounds test which is considered the zero hypothesis. Findings from FMOLS, DOLS and CCR models indicate that maritime transport, trade liberalization and industrial development are the determinants of long-term carbon emissions, just as in the results of the ARDL model. Findings from FMOLS, DOLS and CCR models indicate that maritime transport, trade liberalization and industrial development are the determinants of long-term carbon emissions, just as in the results of the ARDL model. abstract: The major goal of this paper is to focus on the existing literature regarding the linkage between maritime, trade liberalization and industrial development in the context of CO2 by using econometrical model. In this context, it is attempted to reveal the effects of independent variables on CO2 (dependent variable) for China from 1980 to 2013 (annual data) by implementing Phillips-Perron (PP), Zivot-Andrews unit root tests, FMOLS, DOLS, CCR, ARDL and GMM methods. According to results of FMOLS, DOLS and CCR models there is a long-term stable relationship between sea transportation, trade liberalization, industrial development and carbon dioxide emissions which is proved empirically. Similarly, Short term ARDL estimation results reveal that the main determinants of CO2 in the short-run are changed in industrial development and maritime transport at 1% significance level. Table 6 summarizes the short-term ARDL results and the findings regarding the error correction model. According to Table 6, error correction model works in order to reach short-run adjustment. In the short term, approximately 78% of shocks in industrial development, maritime transport and trade liberalization are compensated within a period of time and the system is re-established in the long term. China produced half of the 1.2 million electric media used worldwide; the government directs its attention to the rehabilitation and reuse of all these lithium-ion batteries. Large-scale production of biofuels can still be several years away. Crude oil might be very difficult to promote alternative fuels on a national scale unless crude oil prices surge so high as to become unaffordable. Authorities underline: China will become the world’s number one economy. Now renewable energy will be more important, which should be encouraged to use by government on transportation so as to reduce the CO2 emissions. However, China can be leader excess oil use for transport if they want to dominate the economy worldwide. url: https://doi.org/10.1101/2020.07.13.200386 doi: 10.1101/2020.07.13.200386 id: cord-329855-pr7g6ivu author: Kalfaoglu, Bahire title: T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis date: 2020-05-30 words: 5344.0 sentences: 301.0 pages: flesch: 50.0 cache: ./cache/cord-329855-pr7g6ivu.txt txt: ./txt/cord-329855-pr7g6ivu.txt summary: By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of the transcription factor FOXP3 and interestingly, both the differentiation of regulatory T-cells (Tregs) and Th17 was inhibited. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, while activated CD4+ T-cells continue to promote further viral infection through the production of Furin. These CD25 + activated T-cells are likely to be short-lived and do not initiate FOXP3 transcription in severe COVID-19 patients, while they can differentiate into Tregs in moderate infections. These collectively support that FURIN expression is induced in highly activated non-regulatory CD25 + CD4 + T-cells in severe COVIDOur study has shown that CD4 + T-cells in severe COVID-19 patients have dysregulated activation and differentiation mechanisms. abstract: Severe COVID-19 patients can show respiratory failure, T-cell reduction, and cytokine release syndrome (CRS), which can be fatal in both young and aged patients and is a major concern of the pandemic. However, the pathogenetic mechanisms of CRS in COVID-19 are poorly understood. Here we show single cell-level mechanisms for T-cell dysregulation in severe SARS-CoV-2 infection, and thereby demonstrate the mechanisms underlying T-cell hyperactivation and paralysis in severe COVID-19 patients. By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of the transcription factor FOXP3 and interestingly, both the differentiation of regulatory T-cells (Tregs) and Th17 was inhibited. Meanwhile, highly activated CD4+ T-cells express PD-1 alongside macrophages that express PD-1 ligands in severe patients, suggesting that PD-1-mediated immunoregulation was partially operating. Furthermore, we show that CD25+ hyperactivated T-cells differentiate into multiple helper T-cell lineages, showing multifaceted effector T-cells with Th1 and Th2 characteristics. Lastly, we show that CD4+ T-cells, particularly CD25-expressing hyperactivated T-cells, produce the protease Furin, which facilitates the viral entry of SARS-CoV-2. Collectively, CD4+ T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, while activated CD4+ T-cells continue to promote further viral infection through the production of Furin. Therefore, our study proposes a new model of T-cell hyperactivation and paralysis that drives pulmonary damage, systemic CRS and organ failure in severe COVID-19 patients. url: https://doi.org/10.1101/2020.05.26.115923 doi: 10.1101/2020.05.26.115923 id: cord-263594-jd9ako6c author: Kang, Sisi title: A COVID-19 antibody curbs SARS-CoV-2 nucleocapsid protein-induced complement hyper-activation date: 2020-09-11 words: 2517.0 sentences: 181.0 pages: flesch: 56.0 cache: ./cache/cord-263594-jd9ako6c.txt txt: ./txt/cord-263594-jd9ako6c.txt summary: Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Severe acute 57 respiratory distress syndrome-associated coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein 58 is a highly immunopathogenic and multifunctional viral protein (14) (15) (16) (17) (18) (19) , which elicited high titers 59 of binding antibodies in humoral immune responses (20) (21) (22) . Herein, 66 we report a human mAb derived from COVID-19 convalescent, with specific targeting to SARS-67 CoV-2 N protein and functionally compromising complement hyper-activation ex vivo. Isolation of N protein-directed mAbs 69 To profile antibody response to SARS-CoV-2 N protein in early recovered patients, we collected 70 six convalescent blood samples at seven to 25 days after the onset of the disease symptoms. abstract: Although human antibodies elicited by severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein are profoundly boosted upon infection, little is known about the function of N-directed antibodies. Herein, we isolated and profiled a panel of 32 N protein-specific monoclonal antibodies (mAb) from a quick recovery coronavirus disease-19 (COVID-19) convalescent, who had dominant antibody responses to SARS-CoV-2 N protein rather than to Spike protein. The complex structure of N protein RNA binding domain with the highest binding affinity mAb nCoV396 reveals the epitopes and antigen’s allosteric changes. Functionally, a virus-free complement hyper-activation analysis demonstrates that nCoV396 specifically compromises N protein-induced complement hyper-activation, a risk factor for morbidity and mortality in COVID-19, thus paving the way for functional anti-N mAbs identification. One Sentence Summary B cell profiling, structural determination, and protease activity assays identify a functional antibody to N protein. url: https://doi.org/10.1101/2020.09.10.292318 doi: 10.1101/2020.09.10.292318 id: cord-267831-uu883ofc author: Kang, Yuan-Lin title: Inhibition of PIKfyve kinase prevents infection by Zaire ebolavirus and SARS-CoV-2 date: 2020-06-15 words: 1257.0 sentences: 80.0 pages: flesch: 44.0 cache: ./cache/cord-267831-uu883ofc.txt txt: ./txt/cord-267831-uu883ofc.txt summary: We describe here potent inhibitory effects on content release and infection by chimeric VSV containing the envelope proteins of Zaire ebolavirus (VSV-ZEBOV) or SARS-CoV-2 (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small molecule inhibitors of the main endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase, PIKfyve. 143 All of these viruses require low pH to trigger viral membrane fusion with the endosomal 144 membranes, and as expected, infection was fully blocked by Bafilomycin A1, which 145 inhibits the vacuolar type H + -ATPase (V-ATPase) acidification activity (Fig. 1C) . Mammalian cell morphology and 671 endocytic membrane homeostasis require enzymatically active phosphoinositide 672 5-kinase PIKfyve The phosphatidylinositol-3-phosphate 5-kinase inhibitor 710 apilimod blocks filoviral entry and infection A transmembrane serine protease is linked to the severe 735 acute respiratory syndrome coronavirus receptor and activates virus entry Characterization of severe acute respiratory syndrome-744 associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry abstract: Virus entry is a multistep process. It initiates when the virus attaches to the host cell and ends when the viral contents reach the cytosol. Genetically unrelated viruses can subvert analogous subcellular mechanisms and use similar trafficking pathways for successful entry. Antiviral strategies targeting early steps of infection are therefore appealing, particularly when the probability for successful interference through a common step is highest. We describe here potent inhibitory effects on content release and infection by chimeric VSV containing the envelope proteins of Zaire ebolavirus (VSV-ZEBOV) or SARS-CoV-2 (VSV-SARS-CoV-2) elicited by Apilimod and Vacuolin-1, small molecule inhibitors of the main endosomal Phosphatidylinositol-3-Phosphate/Phosphatidylinositol 5-Kinase, PIKfyve. We also describe potent inhibition of SARS-CoV-2 strain 2019-nCoV/USA-WA1/2020 by Apilimod. These results define new tools for studying the intracellular trafficking of pathogens elicited by inhibition of PIKfyve kinase and suggest the potential for targeting this kinase in developing small-molecule antivirals against SARS-CoV-2. url: https://www.ncbi.nlm.nih.gov/pubmed/32511398/ doi: 10.1101/2020.04.21.053058 id: cord-268339-jxm69ndw author: Karamitros, Timokratis title: SARS-CoV-2 exhibits intra-host genomic plasticity and low-frequency polymorphic quasispecies date: 2020-03-28 words: 3755.0 sentences: 217.0 pages: flesch: 51.0 cache: ./cache/cord-268339-jxm69ndw.txt txt: ./txt/cord-268339-jxm69ndw.txt summary: We analyzed NGS data derived from clinical samples of three Chinese patients infected with SARS-CoV-2, in order to identify smalland large-scale intra-host variations in the viral genome. The isolated SNVs and genomic rearrangements, reflect the intra-patient capacity of the polymorphic quasispecies, which may arise rapidly during the outbreak, allowing immunological escape of the virus, offering resistance to anti-viral drugs and affecting the sensitivity of the molecular diagnostics assays. Here, we explore intra-host genomic variants and low-frequency polymorphic quasispecies in Next Generation Sequencing (NGS) data derived from patients infected by SARS-CoV-2. The S1 subunit consists of a signal peptide and the NT and receptor binding (RB) domains, with the latter sharing only 40% amino acid identity with other SARS-related CoVs. Our analysis revealed that similarly to other genomic regions, the S1 subunit hosts many low-frequency SNVs, characterized by higher density compared to the rest of the S gene sequence (Figure 1-E) . abstract: In December 2019, an outbreak of atypical pneumonia (Coronavirus disease 2019 - COVID-19) associated with a novel coronavirus (SARS-CoV-2) was reported in Wuhan city, Hubei province, China. The outbreak was traced to a seafood wholesale market and human to human transmission was confirmed. The rapid spread and the death toll of the new epidemic warrants immediate intervention. The intra-host genomic variability of SARS-CoV-2 plays a pivotal role in the development of effective antiviral agents and vaccines, but also in the design of accurate diagnostics. We analyzed NGS data derived from clinical samples of three Chinese patients infected with SARS-CoV-2, in order to identify small- and large-scale intra-host variations in the viral genome. We identified tens of low- or higher-frequency single nucleotide variations (SNVs) with variable density across the viral genome, affecting 7 out of 10 protein-coding viral genes. The majority of these SNVs corresponded to missense changes. The annotation of the identified SNVs but also of all currently circulating strain variations revealed colocalization of intra-host but also strain specific SNVs with primers and probes currently used in molecular diagnostics assays. Moreover, we de-novo assembled the viral genome, in order to isolate and validate intra-host structural variations and recombination breakpoints. The bioinformatics analysis disclosed genomic rearrangements over poly-A / poly-U regions located in ORF1ab and spike (S) gene, including a potential recombination hot-spot within S gene. Our results highlight the intra-host genomic diversity and plasticity of SARS-CoV-2, pointing out genomic regions that are prone to alterations. The isolated SNVs and genomic rearrangements, reflect the intra-patient capacity of the polymorphic quasispecies, which may arise rapidly during the outbreak, allowing immunological escape of the virus, offering resistance to anti-viral drugs and affecting the sensitivity of the molecular diagnostics assays. url: https://doi.org/10.1101/2020.03.27.009480 doi: 10.1101/2020.03.27.009480 id: cord-103377-j1mmx7k7 author: Karasik, Agnes title: Activation of the antiviral factor RNase L triggers translation of non-coding mRNA sequences date: 2020-09-11 words: 11779.0 sentences: 646.0 pages: flesch: 58.0 cache: ./cache/cord-103377-j1mmx7k7.txt txt: ./txt/cord-103377-j1mmx7k7.txt summary: Since it was reported that RNase L activation increased translation of 3''UTR regions downstream of stop codons by interfering with factors that promote translation termination (eRF3) or ribosome recycling (ABCE1) (Le Roy et al., 2005) , we assessed the level of ribosome footprints in 3''UTRs. This level was assayed by computing the ratio of footprints in every 3''UTR relative to its respective main ORF within the coding sequence (density ratio, 3''UTR:ORF) for each transcript . The similarity in the effects suggests that translation of non-canonical regions occurs when RNase L is activated via naturally produced 2-5A from broad activation of the antiviral response by double-stranded RNAs. It should be noted that poly I:C treatment did result in slightly elevated 3''UTR ribosome footprints on some genes in a RNase L KO cell line (Supplemental Figure 4A ). abstract: Ribonuclease L (RNase L) is activated as part of the innate immune response and plays an important role in the clearance of viral infections. When activated, it endonucleolytically cleaves both viral and host RNAs, leading to a global reduction in protein synthesis. However, it remains unknown how widespread RNA decay, and consequent changes in the translatome, promote the elimination of viruses. To study how this altered transcriptome is translated, we assayed the global distribution of ribosomes in RNase L activated human cells with ribosome profiling. We found that RNase L activation leads to a substantial increase in the fraction of translating ribosomes in ORFs internal to coding sequences (iORFs) and ORFs within 5’ and 3’ UTRs (uORFs and dORFs). Translation of these alternative ORFs was dependent on RNase L’s cleavage activity, suggesting that mRNA decay fragments are translated to produce short peptides that may be important for antiviral activity. url: https://doi.org/10.1101/2020.09.10.291690 doi: 10.1101/2020.09.10.291690 id: cord-322955-7dw32xby author: Kathwate, Gunderao H title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins date: 2020-06-12 words: 5729.0 sentences: 392.0 pages: flesch: 47.0 cache: ./cache/cord-322955-7dw32xby.txt txt: ./txt/cord-322955-7dw32xby.txt summary: title: In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Those properties are calculated by different methods at IEDB server (http://tools.iedb.org/bcell/ )like Kolaskar-Tongaonkar antigenicity scale provide physiology of the amino acid residues(45), Emini Surface accessible score for accessible surface of the epitope(46), Secondary structure of epitopes also has role in antigenicity. High scored and common peptides predicted by various tools were selected for deriving sequence of potential vaccine candidate. We designed a multi-epitopes vaccine construct from S-protein of SARS-CoV2. From various epitopes predicted by the online server based on common sequence and high score three TCR and two BCR epitopes were selected as part of COVID19 vaccine. This vaccine codes epitopes form S protein of SARS-CoV2 virus for T and B cell receptors. abstract: COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed in E. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity. url: https://doi.org/10.1101/2020.06.03.131755 doi: 10.1101/2020.06.03.131755 id: cord-252097-4kslllaq author: Kaur, S. title: Local computational methods to improve the interpretability and analysis of cryo-EM maps date: 2020-06-19 words: 5987.0 sentences: 312.0 pages: flesch: 54.0 cache: ./cache/cord-252097-4kslllaq.txt txt: ./txt/cord-252097-4kslllaq.txt summary: In this work, we propose 1) approaches to enhance high-resolution features of cryo-EM maps, while preventing map distortions and 2) methods to obtain local B-factors and electron density occupancy maps. Secondly, we also propose approaches to determine local B-factors and density occupancy maps to improve the analysis of cryo-EM reconstructions. The link between the different proposed approaches is the use of the spiral phase transform to estimate a modulation or amplitude map of the cryo-EM reconstruction at different resolutions. In the second row of Figure 2 , we show maps with improved contrast at high-resolution obtained after processing EMD-8441 by the LocSpiral method and by Relion (Fernandez, Luque et al. The common link between all these approaches is the use of the spiral phase transform, which is used to factorize cryo-EM maps into amplitude and phase terms in real space for different resolutions. abstract: Cryo-electron microscopy (cryo-EM) maps usually show heterogeneous distributions of B-factors and electron density occupancies and are typically B-factor sharpened to improve their contrast and interpretability at high-resolutions. However, ‘over-sharpening’ due to the application of a single global B-factor can distort processed maps causing connected densities to appear broken and disconnected. This issue limits the interpretability of cryo-EM maps, i.e. ab initio modelling. In this work, we propose 1) approaches to enhance high-resolution features of cryo-EM maps, while preventing map distortions and 2) methods to obtain local B-factors and electron density occupancy maps. These algorithms have as common link the use of the spiral phase transformation and are called LocSpiral, LocBSharpen, LocBFactor and LocOccupancy. Our results, which include improved maps of recent SARS-CoV-2 structures, show that our methods can improve the interpretability and analysis of obtained reconstructions. url: https://doi.org/10.1101/2020.05.11.088013 doi: 10.1101/2020.05.11.088013 id: cord-304792-8sdxqmkb author: Khan, Md. Abdullah-Al-Kamran title: SARS-CoV-2 proteins exploit host’s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology date: 2020-05-08 words: 2983.0 sentences: 207.0 pages: flesch: 48.0 cache: ./cache/cord-304792-8sdxqmkb.txt txt: ./txt/cord-304792-8sdxqmkb.txt summary: title: SARS-CoV-2 proteins exploit host''s genetic and epigenetic mediators for the annexation of key host signaling pathways that confers its immune evasion and disease pathophysiology In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. We have utilized KEGG mapper tool (Kanehisa and Sato, 2020) for the mapping of 197 deregulated genes SARS-CoV-2 interacting host proteins in different cellular pathways. abstract: The constant rise of the death toll and cases of COVID-19 has made this pandemic a serious threat to human civilization. Understanding of host-SARS-CoV-2 interaction in viral pathogenesis is still in its infancy. In this study we aimed to correlate how SARS-CoV-2 utilizes its proteins for tackling the host immune response; parallelly, how host epigenetic factors might play a role in this pathogenesis was also investigated. We have utilized a blend of computational and knowledgebase approach to elucidate the interplay between host and SARS-CoV-2. Integrating the experimentally validated host interactome proteins and differentially expressed host genes due to SARS-CoV-2 infection, we have taken a blend of computational and knowledgebase approach to delineate the interplay between host and SARS-CoV-2 in various signaling pathways. Also, we have shown how host epigenetic factors are involved in the deregulation of gene expression. Strikingly, we have found that several transcription factors and other epigenetic factors can modulate some immune signaling pathways, helping both host and virus. We have identified miRNA hsa-miR-429 whose transcription factor was also upregulated and targets were downregulated and this miRNA can have pivotal role in suppression of host immune responses. While searching for the pathways in which viral proteins interact with host proteins, we have found pathways like-HIF-1 signaling, autophagy, RIG-I signaling, Toll-like receptor signaling, Fatty acid oxidation/degradation, Il-17 signaling etc significantly associated. We observed that these pathways can be either hijacked or suppressed by the viral proteins, leading to the improved viral survival and life-cycle. Moreover, pathways like-Relaxin signaling in lungs suggests aberration by the viral proteins might lead to the lung pathophysiology found in COVID-19. Also, enrichment analyses suggest that deregulated genes in SARS-CoV-2 infection are involved in heart development, kidney development, AGE-RAGE signaling pathway in diabetic complications etc. might suggest why patients with comorbidities are becoming more prone to SARS-CoV-2 infection. Our results suggest that SARS-CoV-2 integrates its proteins in different immune signaling pathway and other cellular signaling pathways for developing efficient immune evasion mechanisms, while leading the host to more complicated disease condition. Our findings would help in designing more targeted therapeutic interventions against SARS-CoV-2. url: https://doi.org/10.1101/2020.05.06.050260 doi: 10.1101/2020.05.06.050260 id: cord-102511-7zgd45fl author: Khodakov, Dmitriy title: Donut PCR: a rapid, portable, multiplexed, and quantitative DNA detection platform with single-nucleotide specificity date: 2020-05-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Current platforms for molecular analysis of DNA markers are either limited in multiplexing (qPCR, isothermal amplification), turnaround time (microarrays, NGS), quantitation accuracy (isothermal amplification, microarray, nanopore sequencing), or specificity against single-nucleotide differences (microarrays, nanopore sequencing). Here, we present the Donut PCR platform that features high multiplexing, rapid turnaround times, single nucleotide discrimination, and precise quantitation of DNA targets in a portable, affordable, and battery-powered instrument using closed consumables that minimize contamination. We built a bread-board instrument prototype and three assays/chips to demonstrate the capabilities of Donut PCR: (1) a 9-plex mammal identification panel, (2) a 15-plex bacterial identification panel, and (3) a 30-plex human SNP genotyping assay. The limit of detection of the platform is under 10 genomic copies in under 30 minutes, and the quantitative dynamic range is at least 4 logs. We envision that this platform would be useful for a variety of applications where rapid and highly multiplexed nucleic acid detection is needed at the point of care. url: https://doi.org/10.1101/2020.04.24.058453 doi: 10.1101/2020.04.24.058453 id: cord-266869-fs8dn7ir author: Kim, So Young title: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry date: 2020-04-15 words: 3813.0 sentences: 217.0 pages: flesch: 54.0 cache: ./cache/cord-266869-fs8dn7ir.txt txt: ./txt/cord-266869-fs8dn7ir.txt summary: title: Glycosaminoglycan binding motif at S1/S2 proteolytic cleavage site on spike glycoprotein may facilitate novel coronavirus (SARS-CoV-2) host cell entry Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Using a modified version of Autodock Vina tuned for use with carbohydrates (Vina-Carb) [20, 21] , we performed blind docking on the trimeric SARS-CoV-2 SGP model to discover objectively the preferred binding GAG-binding sites on the SGP protein surface. abstract: Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) has resulted in a pandemic and continues to spread around the globe at an unprecedented rate. To date, no effective therapeutic is available to fight its associated disease, COVID-19. Our discovery of a novel insertion of glycosaminoglycan (GAG)-binding motif at S1/S2 proteolytic cleavage site (681-686 (PRRARS)) and two other GAG-binding-like motifs within SARS-CoV-2 spike glycoprotein (SGP) led us to hypothesize that host cell surface GAGs might be involved in host cell entry of SARS-CoV-2. Using a surface plasmon resonance direct binding assay, we found that both monomeric and trimeric SARS-CoV-2 spike more tightly bind to immobilized heparin (KD = 40 pM and 73 pM, respectively) than the SARS-CoV and MERS-CoV SGPs (500 nM and 1 nM, respectively). In competitive binding studies, the IC50 of heparin, tri-sulfated non-anticoagulant heparan sulfate, and non-anticoagulant low molecular weight heparin against SARS-CoV-2 SGP binding to immobilized heparin were 0.056 μM, 0.12 μM, and 26.4 μM, respectively. Finally, unbiased computational ligand docking indicates that heparan sulfate interacts with the GAG-binding motif at the S1/S2 site on each monomer interface in the trimeric SARS-CoV-2 SGP, and at another site (453-459 (YRLFRKS)) when the receptor-binding domain is in an open conformation. Our study augments our knowledge in SARS-CoV-2 pathogenesis and advances carbohydrate-based COVID-19 therapeutic development. url: https://doi.org/10.1101/2020.04.14.041459 doi: 10.1101/2020.04.14.041459 id: cord-335443-iv2gs3kg author: Kim, Youngchang title: Tipiracil binds to uridine site and inhibits Nsp15 endoribonuclease NendoU from SARS-CoV-2 date: 2020-06-28 words: 5464.0 sentences: 333.0 pages: flesch: 57.0 cache: ./cache/cord-335443-iv2gs3kg.txt txt: ./txt/cord-335443-iv2gs3kg.txt summary: Here, we combine crystallography, biochemical and whole cell assays, and show that this compound inhibits SARS-CoV-2 Nsp15 and interacts with the uridine binding pocket of the enzyme''s active site, providing basis for the uracil scaffold-based drug development. For SARS-CoV it was reported that Nsp15 cleaves highly conserved non-translated RNA on (+) sense strand showing that both RNA sequence and structure are important for cleavage 6, 7 . The enzyme cleaves efficiently eicosamer 5''GAACU¯CAU¯GGACCU¯U¯GGCAG3'' at all four uridine sites (Fig. 1) , as well as synthetic EndoU substrate ( 5′-6-FAM-dArU¯dAdA -6-TAMRA-3′ ) 8 in the presence of Mn 2+ and the reaction rate increases with metal ion concentration. SARS-CoV-2 Nsp15 protein was crystallized with 5''UMP, 3''UMP, 5''GpU and Tipiracil using methods described previously 8 and the structures were determined at 1.82 Å, 1.85 Å, 1.97 Å and 1.85 Å, respectively. In the crystal structure of Nsp15/5''GpU, the dinucleoside monophosphate binds to the active site with uracil interacting with Tyr343 and Ser294 (Fig. 4B ), as seen in the Nsp15/5''UMP complex. abstract: SARS-CoV-2 Nsp15 is a uridylate-specific endoribonuclease with C-terminal catalytic domain belonging to the EndoU family. It degrades the polyuridine extensions in (−) sense strand of viral RNA and some non-translated RNA on (+) sense strand. This activity seems to be responsible for the interference with the innate immune response and evasion of host pattern recognition. Nsp15 is highly conserved in coronaviruses suggesting that its activity is important for virus replication. Here we report first structures with bound nucleotides and show that SARS-CoV-2 Nsp15 specifically recognizes U in a pattern previously predicted for EndoU. In the presence of manganese ions, the enzyme cleaves unpaired RNAs. Inhibitors of Nsp15 have been reported but not actively pursued into therapeutics. The current COVID-19 pandemic brought to attention the repurposing of existing drugs and the rapid identification of new antiviral compounds. Tipiracil is an FDA approved drug that is used with trifluridine in the treatment of colorectal cancer. Here, we combine crystallography, biochemical and whole cell assays, and show that this compound inhibits SARS-CoV-2 Nsp15 and interacts with the uridine binding pocket of the enzyme’s active site, providing basis for the uracil scaffold-based drug development. url: https://doi.org/10.1101/2020.06.26.173872 doi: 10.1101/2020.06.26.173872 id: cord-102498-km03fnc4 author: Kinaneh, Safa title: Identification, Localization and Expression of NHE Isoforms in the Alveolar Epithelial Cells date: 2020-09-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Na+/H+ exchangers (NHEs), encoded by Solute Carrier 9A (SLC9A) genes in human, are ubiquitous integral membrane ion transporters that mediate the electroneutral exchange of H+ with Na+ or K+. NHEs, found in the kidney and intestine, play a major role in the process of fluid reabsorption together via Na+,K+-ATPase pump and Na+ channels. Nevertheless, the expression pattern of NHE in the lung and its role in alveolar fluid homeostasis has not been addressed. Therefore, we aimed to examine the expression of NHE specific isoforms in alveolar epithelium cells (AECs), and assess their role in congestive heart failure. Three NHE isoforms were identified in AEC and A549 cell line, at the level of protein and mRNA; NHE1, NHE2 and mainly NHE8, the latter was shown to be localized in the apical membrane of AEC. Treating A549 cells with angiotensin (Ang) II for 1 and 3 hours displayed a significant reduction in NHE8 protein abundance and to lesser extent at 5 hours; however, there was no effect at 24 hours. Moreover, A549 treated overnight with Ang II downregulated NHE8 protein abundance. CHF rats held for 1 week had increased abundance of NHE8 compared to sham operated rats. However, lower abundance of NHE8 was observed in CHF rats held for 4 weeks. Herein we show, for the first time, the expression of a novel NHE isoform by AEC, namely NHE8. Besides being negatively affected by Ang II, NHE8 protein levels were distinctly affected in CHF rats, which may be related to CHF severity. url: https://doi.org/10.1101/2020.09.03.280677 doi: 10.1101/2020.09.03.280677 id: cord-273891-7w334xgt author: Kirchdoerfer, Robert N. title: Receptor binding and proteolysis do not induce large conformational changes in the SARS-CoV spike date: 2018-03-31 words: 3300.0 sentences: 170.0 pages: flesch: 55.0 cache: ./cache/cord-273891-7w334xgt.txt txt: ./txt/cord-273891-7w334xgt.txt summary: The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. Subsequent studies of the highly pathogenic human coronavirus S proteins of SARS-64 CoV 15,22 and MERS-CoV 17,22 showed that these viral S1 RBD do indeed sample an ''up'' 65 conformation where the receptor-binding site is accessible. 70 To examine the hypothesized conformational transitions induced by proteolysis and 71 receptor binding, we used single-particle cryo-EM to determine structures of S in uncleaved, 72 S1/S2 cleaved and ACE2-bound states. Three-dimensional classification of the S1 RBD 73 positions and corresponding atomic protein models revealed that neither ACE2-binding nor 74 trypsin cleavage at the S1/S2 boundary induced substantial conformational changes in the CoV may use a distinct mechanism of FP2 membrane insertion. Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein 381 reveal a prerequisite conformational state for receptor binding abstract: Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S undergoes two proteolytic cleavages at S1/S2 and S2’ sites necessary for efficient membrane fusion. Here, we present a cryo-EM analysis of the trimeric SARS-CoV S interactions with ACE2 and of the trypsin-cleaved S. Surprisingly, neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within S or expose the secondary cleavage site, S2’. These observations suggest that S2’ cleavage does not occur in the S prefusion conformation and that additional triggers may be required. url: https://doi.org/10.1101/292672 doi: 10.1101/292672 id: cord-319100-3gdawhfn author: Kirkland, P.D. title: The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2 and other viruses date: 2020-06-10 words: 4624.0 sentences: 204.0 pages: flesch: 49.0 cache: ./cache/cord-319100-3gdawhfn.txt txt: ./txt/cord-319100-3gdawhfn.txt summary: authors: Kirkland, P.D.; Frost, M.J. title: The impact of viral transport media on PCR assay results for the detection of nucleic acid from SARS-CoV-2 and other viruses Also of concern are recommendations (3, 4) to include foetal bovine serum (fbs) as a source of protein to enhance the stabilising properties of VTMs. This report documents observations of the adverse impact of certain VTMs on real time reverse transcription PCR (qRT-PCR) assays for the detection of SARS-CoV-2 virus as well as on a Type A influenza virus and a herpesvirus and discuss the broader implications of the inclusion of foetal bovine serum as a protein supplement to VTMs. During the initial investigation, purified RNA from an Australian isolate (WMD DC1) of SARS-CoV-2 was supplied to the Elizabeth Macarthur Agriculture Institute (EMAI) by the Institute of Clinical Pathology and Medical Research (ICPMR), Westmead, New South Wales (NSW). abstract: During the 2020 SARS-Cov-2 pandemic, there has been an acute shortage of viral transport medium. Many different products have been used to meet the demands of large-scale diagnostic and surveillance testing. The stability of SARS-Cov-2 RNA was assessed in several commercially produced transport media and an in-house solution. Coronavirus RNA was rapidly destroyed in the commercial transport media though the deleterious effects on intact virus were limited. Similar results were obtained for a Type A influenza virus. There was reduced detection of both virus and nucleic acid when a herpesvirus sample and purified DNA were tested. Collectively these data showed that the commercial viral transport media contained nucleases or similar substances and may seriously compromise diagnostic and epidemiological investigations. Recommendations to include foetal bovine serum as a source of protein to enhance the stabilising properties of viral transport media are contraindicated. Almost all commercial batches of foetal bovine serum contain pestiviruses and at times other bovine viruses. In addition to the potential for there to be nucleases in the transport medium, the presence of these viruses and other extraneous nucleic acid in samples may compromise the interpretation of sequence data. The inclusion of foetal bovine serum presents a biosecurity risk for the movement of animal pathogens and renders these transport media unsuitable for animal disease diagnostic applications. While these transport media may be suitable for virus culture purposes, there could be misleading results if used for nucleic acid-based tests. Therefore, these products should be evaluated to ensure fitness for purpose. url: https://doi.org/10.1101/2020.06.09.142323 doi: 10.1101/2020.06.09.142323 id: cord-286810-kq2gu5cc author: Klein, Joshua A. title: Assignment of coronavirus spike protein site-specific glycosylation using GlycReSoft date: 2020-05-31 words: 2581.0 sentences: 145.0 pages: flesch: 50.0 cache: ./cache/cord-286810-kq2gu5cc.txt txt: ./txt/cord-286810-kq2gu5cc.txt summary: We summarize the principles for glycopeptide data analysis and show use of our GlycReSoft tool to analyze SARS-CoV-2 spike protein site-specific glycosylation. A glycoproteomics database search engine includes functions for (i) search space construction, (ii) mass spectrum pre-processing, (iii) a scoring model that evaluates Glycopeptide LC-MS algorithms p. The search space uses an input protein list to calculate proteolytic peptides with a list of constant and variable modification rules that include glycosylation. The use of a long LC gradient combined with a single HCD collision energy value of 50% maximized the number of glycopeptides that were While the glycopeptide tandem mass spectrum shown in Figure 3 was acquired using stepped collision energy, the S protein tandem MS data were acquired using HCD set at 50%. We show an example of the use of GlycReSoft to assign SARS-CoV-2 S protein glycosylation from a published data set in which we identify sulfated N-glycans not identified in the original manuscript. abstract: Widely-available LC-MS instruments and methods allow users to acquire glycoproteomics data. Complex glycans, however, add a dimension of complexity to the data analysis workflow. In a sense, complex glycans are post-translationally modified post-translational modifications, reflecting a series of biosynthetic reactions in the secretory pathway that are spatially and temporally regulated. One problem is that complex glycan is micro-heterogeneous, multiplying the complexity of the proteome. Another is that glycopeptide glycans undergo dissociation during tandem MS that must be considered for tandem MS interpretation algorithms and quantitative tools. Fortunately, there are a number of algorithmic tools available for analysis of glycoproteomics LC-MS data. We summarize the principles for glycopeptide data analysis and show use of our GlycReSoft tool to analyze SARS-CoV-2 spike protein site-specific glycosylation. url: https://doi.org/10.1101/2020.05.31.125302 doi: 10.1101/2020.05.31.125302 id: cord-102691-pij32hbi author: Klein, Steffen title: Post-correlation on-lamella cryo-CLEM reveals the membrane architecture of lamellar bodies date: 2020-08-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lamellar bodies (LBs) are surfactant-rich organelles in alveolar cells. LBs disassemble into a lipid-protein network that reduces surface tension and facilitates gas exchange in the alveolar cavity. Current knowledge of LB architecture is predominantly based on electron microscopy studies using disruptive sample preparation methods. We established and validated a post-correlation on-lamella cryo-correlative light and electron microscopy approach for cryo-FIB milled cells to structurally characterize and validate the identity of LBs in their unperturbed state. Using deconvolution and 3D image registration, we were able to identify fluorescently labeled membrane structures analyzed by cryo-electron tomography. In situ cryo-electron tomography of A549 cells as well as primary Human Small Airway Epithelial Cells revealed that LBs are composed of membrane sheets frequently attached to the limiting membrane through “T”-junctions. We report a so far undescribed outer membrane dome protein complex (OMDP) on the limiting membrane of LBs. Our data suggest that LB biogenesis is driven by parallel membrane sheet import and by the curvature of the limiting membrane to maximize lipid storage capacity. url: https://doi.org/10.1101/2020.02.27.966739 doi: 10.1101/2020.02.27.966739 id: cord-342657-od48cntc author: Klemm, Theresa title: Mechanism and inhibition of SARS-CoV-2 PLpro date: 2020-06-19 words: 1704.0 sentences: 110.0 pages: flesch: 65.0 cache: ./cache/cord-342657-od48cntc.txt txt: ./txt/cord-342657-od48cntc.txt summary: More variability is seen in MERS PLpro, which binds to ubiquitin and 138 ISG15 CTD similarly through its ability to ''close'' the Fingers subdomain 26 (see 139 discussion in Extended Data Fig. 4) . A 1536-well low-volume high-throughput assay previously used to identify inhibitors Together, our data suggests that a repurposing strategy using 3727 unique known 199 drugs towards SARS2 PLpro is unlikely to yield drug candidates, and highlights the 200 importance of a counterscreen in assessing the validity of hits coming from a screen 201 of known drugs before any conclusions on their therapeutic potential can be drawn. Since it had previously 237 been shown that these inhibitors are specific for PLpro over human DUBs 1 (also see 238 Figure 3b ) and since treatment with rac5c did not affect Lys48-linked polyubiquitin in 239 the absence of nsp3 expression (Extended Data Fig 8f) , the effect of rac5c on 240 Lys48-polyubiquitin is likely due to inhibition of nsp3/PLpro. abstract: Coronaviruses, including SARS-CoV-2, encode multifunctional proteases that are essential for viral replication and evasion of host innate immune mechanisms. The papain-like protease PLpro cleaves the viral polyprotein, and reverses inflammatory ubiquitin and anti-viral ubiquitin-like ISG15 protein modifications1,2. Drugs that target SARS-CoV-2 PLpro (hereafter, SARS2 PLpro) may hence be effective as treatments or prophylaxis for COVID-19, reducing viral load and reinstating innate immune responses3. We here characterise SARS2 PLpro in molecular and biochemical detail. SARS2 PLpro cleaves Lys48-linked polyubiquitin and ISG15 modifications with high activity. Structures of PLpro bound to ubiquitin and ISG15 reveal that the S1 ubiquitin binding site is responsible for high ISG15 activity, while the S2 binding site provides Lys48 chain specificity and cleavage efficiency. We further exploit two strategies to target PLpro. A repurposing approach, screening 3727 unique approved drugs and clinical compounds against SARS2 PLpro, identified no compounds that inhibited PLpro consistently or that could be validated in counterscreens. More promisingly, non-covalent small molecule SARS PLpro inhibitors were able to inhibit SARS2 PLpro with high potency and excellent antiviral activity in SARS-CoV-2 infection models. url: https://doi.org/10.1101/2020.06.18.160614 doi: 10.1101/2020.06.18.160614 id: cord-102356-knvfbuzv author: Knyazev, Sergey title: Accurate assembly of minority viral haplotypes from next-generation sequencing through efficient noise reduction date: 2020-10-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Rapidly evolving RNA viruses continuously produce minority haplotypes that can become dominant if they are drug-resistant or can better evade the immune system. Therefore, early detection and identification of minority viral haplotypes may help to promptly adjust the patient's treatment plan preventing potential disease complications. Minority haplotypes can be identified using next-generation sequencing (NGS), but sequencing noise hinders accurate identification. The elimination of sequencing noise is a non-trivial task that still remains open. Here we propose CliqueSNV based on extracting pairs of statistically linked mutations from noisy reads. This effectively reduces sequencing noise and enables identifying minority haplotypes with the frequency below the sequencing error rate. We comparatively assess the performance of CliqueSNV using an in vitro mixture of nine haplotypes that were derived from the mutation profile of an existing HIV patient. We show that CliqueSNV can accurately assemble viral haplotypes with frequencies as low as 0.1% and maintains consistent performance across short and long bases sequencing platforms. url: https://doi.org/10.1101/264242 doi: 10.1101/264242 id: cord-102612-xx5l8r9e author: Kodani, Andrew title: Zika virus alters centrosome organization to suppress the innate immune response date: 2020-09-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Zika virus (ZIKV) is a flavivirus transmitted via mosquitoes and sex to cause congenital neurodevelopmental defects, including microcephaly. Inherited forms of microcephaly (MCPH) are associated with disrupted centrosome organization. Similarly, we found that ZIKV infection disrupted centrosome organization. ZIKV infection disrupted the organization of centrosomal proteins including CEP63, a MCPH-associated protein. The ZIKV nonstructural protein NS3 bound CEP63, and expression of NS3 was sufficient to alter centrosome architecture and CEP63 localization. Loss of CEP63 suppressed ZIKV-induced centrosome disorganization, indicating that ZIKV requires CEP63 to disrupt centrosome organization. ZIKV infection or loss of CEP63 decreased the centrosomal localization and stability of TANK-binding kinase 1 (TBK1), a regulator of the innate immune response. ZIKV infection or loss of CEP63 also increased the centrosomal accumulation of the CEP63 interactors, Mindbomb1 (MIB1) and DTX4, ubiquitin ligases that respectively activate and degrade TBK1. Therefore, we propose that ZIKV NS3 binds CEP63 to increase centrosomal DTX4 localization and destabilization of TBK1, thereby tempering the innate immune response. In addition to identifying a mechanism by which CEP63 controls the innate immune responses in ZIKV infection, we propose that the altered centrosomal organization caused by altered CEP63 function may contribute to ZIKV-associated microcephaly. url: https://doi.org/10.1101/2020.09.15.298083 doi: 10.1101/2020.09.15.298083 id: cord-340291-bah2ege0 author: Kohmer, Niko title: Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity date: 2020-05-10 words: 1001.0 sentences: 63.0 pages: flesch: 55.0 cache: ./cache/cord-340291-bah2ege0.txt txt: ./txt/cord-340291-bah2ege0.txt summary: With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. With exception of one sample, all positive tested samples in the analysed cohort, using the 37 commercially available assays examined (including the in-house developed IFA), demonstrated 38 neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-39 there is an increasing demand in the detection of antibodies -especially of IgG antibodies. Currently there are many S 57 protein based commercially or in-house developed assays available, but there is limited data on how 58 these tests perform with clinical samples and if the detected IgG antibodies provide protective 59 abstract: As the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to severe clinical course, who required an in-patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8 to 100% for the later period (days 10-18) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated. url: https://doi.org/10.1101/2020.05.08.085506 doi: 10.1101/2020.05.08.085506 id: cord-280025-4hmecfi0 author: Korber, B title: Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2 date: 2020-05-05 words: 11173.0 sentences: 524.0 pages: flesch: 54.0 cache: ./cache/cord-280025-4hmecfi0.txt txt: ./txt/cord-280025-4hmecfi0.txt summary: We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. Over the past two months, the HIV database team at Los Alamos National Laboratory has turned to developing an analysis pipeline to track in real time the evolution of the SARS-CoV-2 Spike (S) protein in the COVID-19 pandemic, using the Global Initiative for Sharing All Influenza Data GISAID SARS-CoV-2 sequence database as our baseline (Sup. Item 1 is the GISAID acknowledgments table, listing all the groups who contribute sequences to this global effort) (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) . GISAID is the primary SARS-CoV-2 sequence database resource, and our intent is to complement what they provide with visualizations and summary data specifically intended to support the immunology and vaccine communities, and to alert the broader community to changes in frequency of mutations that might signal positive selection and a change in either viral phenotype or antigenicity. abstract: We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions. url: https://doi.org/10.1101/2020.04.29.069054 doi: 10.1101/2020.04.29.069054 id: cord-330031-c1n994j6 author: Kratzel, Annika title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols date: 2020-03-17 words: 752.0 sentences: 51.0 pages: flesch: 50.0 cache: ./cache/cord-330031-c1n994j6.txt txt: ./txt/cord-330031-c1n994j6.txt summary: title: Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. We show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission. The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-2 CoV-2) causing COVID-19 is a major burden for health care systems worldwide. The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-2 CoV-2) causing COVID-19 is a major burden for health care systems worldwide. We therefore determined the virucidal activity of two 5 alcohol-based hand rub solutions for hand disinfection recommended by the World 6 Hand Hygiene in Health Care'' suggests two alcohol-based formulations for hand 9 sanitization to reduce pathogen infectivity and spreading. abstract: The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a major burden for health care systems worldwide. It is important to address if the current infection control instructions based on active ingredients are sufficient. We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. Efficient SARS-CoV-2 inactivation was demonstrated for all tested alcohol-based disinfectants. These findings show the successful inactivation of SARS-CoV-2 for the first time and provide confidence in its use for the control of COVID-19. Importance The current COVID-19 outbreak puts a huge burden on the world’s health care systems. Without effective therapeutics or vaccines being available, effective hygiene measure are of utmost importance to prevent viral spreading. It is therefore crucial to evaluate current infection control strategies against SARS-CoV-2. We show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission. url: https://doi.org/10.1101/2020.03.10.986711 doi: 10.1101/2020.03.10.986711 id: cord-333703-1ku3jc9s author: Kraus, Aurora title: A zebrafish model for COVID-19 recapitulates olfactory and cardiovascular pathophysiologies caused by SARS-CoV-2 date: 2020-11-08 words: 8452.0 sentences: 605.0 pages: flesch: 57.0 cache: ./cache/cord-333703-1ku3jc9s.txt txt: ./txt/cord-333703-1ku3jc9s.txt summary: Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. In mice and humans, ace2 expression is detected in 121 sustentacular cells, olfactory stem cells known as horizontal and globose basal cells in the 122 olfactory epithelium, and vascular cells (pericytes) in the olfactory bulb (Brann et al., 2020 The present study reports for the first time that zebrafish larvae exposed to SARS-CoV-2 appear 134 to mount innate immune responses that resemble cytokine responses of mild COVID-19 patients. There are copious amounts of immune cells in the teleost olfactory organ ( Intranasal delivery of SARS-CoV-2 S RBD induces inflammatory responses and 318 widespread loss of olfactory receptor expression in adult zebrafish olfactory organ 319 320 abstract: The COVID-19 pandemic has prompted the search for animal models that recapitulate the pathophysiology observed in humans infected with SARS-CoV-2 and allow rapid and high throughput testing of drugs and vaccines. Exposure of larvae to SARS-CoV-2 Spike (S) receptor binding domain (RBD) recombinant protein was sufficient to elevate larval heart rate and treatment with captopril, an ACE inhibitor, reverted this effect. Intranasal administration of SARS-CoV-2 S RBD in adult zebrafish recombinant protein caused severe olfactory and mild renal histopathology. Zebrafish intranasally treated with SARS-CoV-2 S RBD became hyposmic within minutes and completely anosmic by 1 day to a broad-spectrum of odorants including bile acids and food. Single cell RNA-Seq of the adult zebrafish olfactory organ indicated widespread loss of expression of olfactory receptors as well as inflammatory responses in sustentacular, endothelial, and myeloid cell clusters. Exposure of wildtype zebrafish larvae to SARS-CoV-2 in water did not support active viral replication but caused a sustained inhibition of ace2 expression, triggered type 1 cytokine responses and inhibited type 2 cytokine responses. Combined, our results establish adult and larval zebrafish as useful models to investigate pathophysiological effects of SARS-CoV-2 and perform pre-clinical drug testing and validation in an inexpensive, high throughput vertebrate model. url: https://doi.org/10.1101/2020.11.06.368191 doi: 10.1101/2020.11.06.368191 id: cord-265418-yqe9vdj1 author: Kumar, Nilesh title: Integrative Network Biology Framework Elucidates Molecular Mechanisms of SARS-CoV-2 Pathogenesis date: 2020-04-11 words: 5288.0 sentences: 363.0 pages: flesch: 54.0 cache: ./cache/cord-265418-yqe9vdj1.txt txt: ./txt/cord-265418-yqe9vdj1.txt summary: Integrated interactome-transcriptome analysis to generate Calu-3-specific humanIt is likely that the outcome of SARS-CoV-2 infection can largely be determined by the interaction patterns of host proteins and viral factors. By integrating this Calu-3 co-expression network with SIPs-derived PPI subnetwork, we generated Calu-3-specific human-SARS-CoV-2 Interactome (CSI) that contains 214 SIPs interacting with their first and second neighbors make a network of 4,123 nodes and 14,650 edges (Fig. 1c, Supplementary Data 1) . We showed that CSI follows a power law degree distribution with a few nodes harboring increased connectivity, and thus exhibits properties of a scale-free network (r 2 = 0.91; (Fig. 1d , Supplementary Data 1), similar to the previously generated other human-viral interactomes 12, 13, 14, 15, 16, 17, 18, 19, 20, 24, 25, 26, 27, 28 . In conclusion, we generated a human-SARS-CoV-2 interactome, integrated virusrelated transcriptome to interactome, discover COVID-19 pertinent structural and functional modules, identify high-value viral targets, and perform dynamic transcriptional modeling. abstract: COVID-19 (Coronavirus disease 2019) is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While the pathophysiology of this deadly virus is complex and largely unknown, we employ a network biology-fueled approach and integrated multiomics data pertaining to lung epithelial cells-specific coexpression network and human interactome to generate Calu-3-specific human-SARS-CoV-2 Interactome (CSI). Topological clustering and pathway enrichment analysis show that SARS-CoV-2 target central nodes of host-viral network that participate in core functional pathways. Network centrality analyses discover 28 high-value SARS-CoV-2 targets, which are possibly involved in viral entry, proliferation and survival to establish infection and facilitate disease progression. Our probabilistic modeling framework elucidates critical regulatory circuitry and molecular events pertinent to COVID-19, particularly the host modifying responses and cytokine storm. Overall, our network centric analyses reveal novel molecular components, uncover structural and functional modules, and provide molecular insights into SARS-CoV-2 pathogenicity. url: https://doi.org/10.1101/2020.04.09.033910 doi: 10.1101/2020.04.09.033910 id: cord-311214-eqwxkwqa author: Kumar, Roshan title: Comparative Genomic Analysis of Rapidly Evolving SARS-CoV-2 Viruses Reveal Mosaic Pattern of Phylogeographical Distribution date: 2020-04-16 words: 2724.0 sentences: 184.0 pages: flesch: 60.0 cache: ./cache/cord-311214-eqwxkwqa.txt txt: ./txt/cord-311214-eqwxkwqa.txt summary: Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. A manually annotated reference database was generated using the Genbank 128 file of Severe acute respiratory syndrome coronavirus 2 isolate-SARS-CoV-129 2/SH01/human/2020/CHN (Accession number: MT121215) and open reading frames (ORFs) 130 were predicted against the formatted database using prokka (-gcode 1) [22] . All these isolates 189 were found to harbor 9 open reading frames coding for ORF1a (13218 bp) and ORF1b (7788 190 bp) polyproteins, surface glycoprotein or S-protein (3822 bp), ORF3a protein (828 bp Our analysis revealed that strains of human infecting SARS-CoV-2 are novel and highly 201 identical (>99.9%). In this study, the analysis was 358 performed on the genomes of the novel SARS-CoV-2 isolates recently reported from different 359 countries to understand viral pathogenesis. abstract: The Coronavirus Disease-2019 (COVID-19) that started in Wuhan, China in December 2019 has spread worldwide emerging as a global pandemic. The severe respiratory pneumonia caused by the novel SARS-CoV-2 has so far claimed more than 60,000 lives and has impacted human lives worldwide. However, as the novel SARS-CoV-2 displays high transmission rates, their underlying genomic severity is required to be fully understood. We studied the complete genomes of 95 SARS-CoV-2 strains from different geographical regions worldwide to uncover the pattern of the spread of the virus. We show that there is no direct transmission pattern of the virus among neighboring countries suggesting that the outbreak is a result of travel of infected humans to different countries. We revealed unique single nucleotide polymorphisms (SNPs) in nsp13-16 (ORF1b polyprotein) and S-Protein within 10 viral isolates from the USA. These viral proteins are involved in RNA replication, indicating highly evolved viral strains circulating in the population of USA than other countries. Furthermore, we found an amino acid addition in nsp16 (mRNA cap-1 methyltransferase) of the USA isolate (MT188341) leading to shift in amino acid frame from position 2540 onwards. Through the construction of SARS-CoV-2-human interactome, we further revealed that multiple host proteins (PHB, PPP1CA, TGF-β, SOCS3, STAT3, JAK1/2, SMAD3, BCL2, CAV1 & SPECC1) are manipulated by the viral proteins (nsp2, PL-PRO, N-protein, ORF7a, M-S-ORF3a complex, nsp7-nsp8-nsp9-RdRp complex) for mediating host immune evasion. Thus, the replicative machinery of SARS-CoV-2 is fast evolving to evade host challenges which need to be considered for developing effective treatment strategies. url: https://doi.org/10.1101/2020.03.25.006213 doi: 10.1101/2020.03.25.006213 id: cord-340240-dk48pdqa author: Kuo, Tsun-Yung title: Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 date: 2020-08-11 words: 1240.0 sentences: 91.0 pages: flesch: 53.0 cache: ./cache/cord-340240-dk48pdqa.txt txt: ./txt/cord-340240-dk48pdqa.txt summary: title: Development of CpG-adjuvanted stable prefusion SARS-CoV-2 spike antigen as a subunit vaccine against COVID-19 S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. In this study, we present data from preclinical studies aimed at developing a COVID-19 candidate subunit 84 vaccine using CHO cell-expressed SARS-CoV-2 S-2P antigen combined with various adjuvants. We have 85 shown that S-2P, when mixed with CpG 1018 and aluminum hydroxide adjuvants, was most effective in 86 inducing antibodies that neutralized pseudovirus and wild-type live virus while minimizing Th2-biased 87 responses with no vaccine-related adverse effects. Previous studies showed that the lung-infiltrating eosinophils were a common 308 indication of Th2-biased immune responses seen in animal models testing SARS-CoV vaccine candidates [22] . abstract: The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 is a worldwide health emergency. The immense damage done to public health and economies has prompted a global race for cures and vaccines. In developing a COVID-19 vaccine, we applied technology previously used for MERS-CoV to produce a prefusion-stabilized SARS-CoV-2 spike protein by adding two proline substitutions at the top of the central helix (S-2P). To enhance immunogenicity and mitigate the potential vaccine-induced immunopathology, CpG 1018, a Th1-biasing synthetic toll-like receptor 9 (TLR9) agonist was selected as an adjuvant candidate. S-2P was combined with various adjuvants, including CpG 1018, and administered to mice to test its effectiveness in eliciting anti-SARS-CoV-2 neutralizing antibodies. S-2P in combination with CpG 1018 and aluminum hydroxide (alum) was found to be the most potent immunogen and induced high titer of spike-specific antibodies in sera of immunized mice. The neutralizing abilities in pseudotyped lentivirus reporter or live wild-type SARS-CoV-2 were measured with reciprocal inhibiting dilution (ID50) titers of 5120 and 2560, respectively. In addition, the antibodies elicited were able to cross-neutralize pseudovirus containing the spike protein of the D614G variant, indicating the potential for broad spectrum protection. A marked Th-1 dominant response was noted from cytokines secreted by splenocytes of mice immunized with CpG 1018 and alum. No vaccine-related serious adverse effects were found in the dose-ranging study in rats administered single- or two-dose regimens with up to 50 μg of S-2P combined with CpG 1018 alone or CpG 1018 with alum. These data support continued development of CHO-derived S-2P formulated with CpG 1018/alum as a candidate vaccine to prevent COVID-19 disease. url: https://doi.org/10.1101/2020.08.11.245704 doi: 10.1101/2020.08.11.245704 id: cord-103773-1b961lfz author: Kurokawa, Shunji title: In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model date: 2020-05-29 words: 2917.0 sentences: 170.0 pages: flesch: 39.0 cache: ./cache/cord-103773-1b961lfz.txt txt: ./txt/cord-103773-1b961lfz.txt summary: title: In vivo recellularization of xenogeneic vascular grafts decellularized with high hydrostatic pressure method in a porcine carotid arterial interpose model In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries then evaluated graft patency, ECM preservation and recellularization. Scanning electron microscopy on luminal surface of implanted grafts exhibited cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Elastica van Gieson staining and Sirius red staining exhibited a fair preservation of elastin layer (internal elastic lamina), tunica media consisted of collagen fibers and stratified elastin layers in HHP-decellularized grafts, and recellularization at 4 weeks after implantation, respectively (Fig. 4B) . The luminal surface of decellularized bovine graft implanted at porcine carotid artery for 4 weeks showed endothelium with cobblestone-like appearance by fair recellularization similar with those in bovine and porcine native arteries (recipient animal) (Fig. 5A , C, D). abstract: Autologous vascular grafts are widely used in revascularization surgeries for small caliber targets. However, the availability of autologous conduits might be limited due to prior surgeries or the quality of vessels. Xenogeneic decellularized vascular grafts from animals potentially substitute for autologous vascular grafts. Decellularization with high hydrostatic pressure (HHP) is reported to highly preserve extracellular matrix (ECM) which would be feasible for recellularization and vascular remodeling after implantation. In the present study, we conducted xenogeneic implantation of HHP-decellularized bovine vascular grafts from dorsalis pedis arteries to porcine carotid arteries then evaluated graft patency, ECM preservation and recellularization. Surgical procedure not to damage luminal surface of the grafts from drying significantly increased the graft patency at 4 weeks after implantation (P = 0.0079). After the technical improvement, all grafts (N = 5) were patent with mild stenosis due to intimal hyperplasia at 4 weeks after implantation. Neither aneurysmal change nor massive thrombosis was observed even without administration of anticoagulants nor anti-platelet agents. Elastica van Gieson and Sirius-red stainings revealed fair preservation of ECM proteins including elastin and collagen after implantation. Luminal surface of grafts was thoroughly covered with von Willebrand factor-positive endothelium. Scanning electron microscopy on luminal surface of implanted grafts exhibited cobblestone-like endothelial cell layer which is similar to native vascular endothelium. Recellularization of tunica media with alpha-smooth muscle actin-positive smooth muscle cells was partly observed. Thus, we confirmed that HHP-decellularized grafts are feasible for xenogeneic implantation accompanied by recellularization by recipient cells. url: https://doi.org/10.1101/2020.05.29.123018 doi: 10.1101/2020.05.29.123018 id: cord-103517-1itisiup author: Kwesi-Maliepaard, Eliza Mari title: The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells date: 2019-11-18 words: 7875.0 sentences: 419.0 pages: flesch: 54.0 cache: ./cache/cord-103517-1itisiup.txt txt: ./txt/cord-103517-1itisiup.txt summary: T-cell specific ablation of Dot1L resulted in loss of naïve CD8+ T cells and premature differentiation towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. Analysis of CD8 + T cell subsets in the spleen revealed that Dot1L-KO mice showed a severe loss of naïve (CD44 -CD62L + ) CD8 + T (T N ) cells which was linked to a massive gain of the CD44 + CD62L + phenotype, a feature of central memory T cells (T CM ; Fig. 1A -B). To determine whether peripheral T AIM cells observed in the Dot1L-KO setting originate intrathymically, as reported previously for IL-4 dependent innate memory T cells 3 , we compared RNA-Seq data from SP CD8 + thymocytes from KO and WT mice. abstract: Cytotoxic T-cell differentiation is guided by epigenome adaptations but how epigenetic mechanisms control lymphocyte development has not been well defined. Here we show that the histone methyltransferase DOT1L, which marks the nucleosome core on active genes, safeguards normal differentiation of CD8+ T cells. T-cell specific ablation of Dot1L resulted in loss of naïve CD8+ T cells and premature differentiation towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Without DOT1L, the memory-like CD8+ cells fail to acquire full effector functions in vitro and in vivo. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. Through our study DOT1L is emerging as a central player in physiology of CD8+ T cells, acting as a barrier to prevent premature differentiation and supporting the licensing of the full effector potential of cytotoxic T cells. url: https://doi.org/10.1101/826255 doi: 10.1101/826255 id: cord-298321-8871aifz author: Laamarti, Meriem title: Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum date: 2020-07-01 words: 2142.0 sentences: 123.0 pages: flesch: 58.0 cache: ./cache/cord-298321-8871aifz.txt txt: ./txt/cord-298321-8871aifz.txt summary: The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Our recent study (13) based on the analysis of 30,983 genomes of SARS-CoV-2 variants belonging to 80 countries, revealed 5.67% of total mutations with a frequency greater than 1% of all the sequences analyzed suggesting that this virus is not yet adapted to its host. In all Moroccan SARS-CoV-2 genomes, the analysis of genetic variants revealed 61 mutations compared to the reference sequence (Fig 1) , including 29 non-syn(Fig 2A) . abstract: In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2. url: https://doi.org/10.1101/2020.06.30.181123 doi: 10.1101/2020.06.30.181123 id: cord-288824-sygnmiun author: Lam, SD title: SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals date: 2020-08-19 words: 7353.0 sentences: 412.0 pages: flesch: 54.0 cache: ./cache/cord-288824-sygnmiun.txt txt: ./txt/cord-288824-sygnmiun.txt summary: To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We correlated changes in the energy of the complex with changes in the structure of ACE2, chemical properties of residues in the binding interface, and experimental COVID-19 infection phenotypes from in vivo and in vitro animal studies. We used multiple methods to assess the relative change in binding energy (ΔΔG) of the SARS-CoV-2 S-protein:ACE2 complex following mutations in DC residues and DCEX residues that are likely to influence binding. Irrespective of host, the SARS-CoV-2 spike receptor binding domain is conserved (Fig. 4b) across tested human and animal associated SARS-CoV-2, suggesting mutations in the RBD are not required for infections observed in non-human species to date. abstract: SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance. url: https://doi.org/10.1101/2020.05.01.072371 doi: 10.1101/2020.05.01.072371 id: cord-329102-2y49kcwu author: Lan, Tammy C. T. title: Structure of the full SARS-CoV-2 RNA genome in infected cells date: 2020-06-30 words: 9315.0 sentences: 507.0 pages: flesch: 61.0 cache: ./cache/cord-329102-2y49kcwu.txt txt: ./txt/cord-329102-2y49kcwu.txt summary: We evaluated the robustness of our in-cell data derived genome-wide model by varying two critical RNA folding parameters used by RNAstructure: 1) the maximum allowed distance for base pairing and 2) the threshold for DMS signal normalization. Previous studies that computationally predicted genome-wide SARS-Cov-2 RNA structures used 1) RNAz, a thermodynamic-based model that additionally takes sequence alignment and considers base pairing conservation (Gruber et al., 2010; Rangan, Zheludev and Das, 2020) , and 2) Contrafold, which predicts RNA secondary structures without physics-based models and instead uses learned parameters based on known structures (Do, Woods and Batzoglou, 2006) . Interestingly, in silico predictions of the RNA structure of the SARS-CoV-2 genome using RNAz (Rangan, Zheludev and Das, 2020) and ScanFold (Andrews et al., 2020) do not find the 3-stem pseudoknot but instead support our in-cell model of Alternative Stem 1. abstract: SARS-CoV-2 is a betacoronavirus with a single-stranded, positive-sense, 30-kilobase RNA genome responsible for the ongoing COVID-19 pandemic. Currently, there are no antiviral drugs or vaccines with proven efficacy, and development of these treatments are hampered by our limited understanding of the molecular and structural biology of the virus. Like many other RNA viruses, RNA structures in coronaviruses regulate gene expression and are crucial for viral replication. Although genome and transcriptome data were recently reported, there is to date little experimental data on predicted RNA structures in SARS-CoV-2 and most putative regulatory sequences are uncharacterized. Here we report the secondary structure of the entire SARS-CoV-2 genome in infected cells at single nucleotide resolution using dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq). Our results reveal previously undescribed structures within critical regulatory elements such as the genomic transcription-regulating sequences (TRSs). Contrary to previous studies, our in-cell data show that the structure of the frameshift element, which is a major drug target, is drastically different from prevailing in vitro models. The genomic structure detailed here lays the groundwork for coronavirus RNA biology and will guide the design of SARS-CoV-2 RNA-based therapeutics. url: https://doi.org/10.1101/2020.06.29.178343 doi: 10.1101/2020.06.29.178343 id: cord-323041-wf0hlhim author: Larsen, Mads Delbo title: Afucosylated immunoglobulin G responses are a hallmark of enveloped virus infections and show an exacerbated phenotype in COVID-19 date: 2020-05-18 words: 1413.0 sentences: 92.0 pages: flesch: 56.0 cache: ./cache/cord-323041-wf0hlhim.txt txt: ./txt/cord-323041-wf0hlhim.txt summary: Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. Moreover, we have reported the lowered IgG-Fc fucosylation to be one of the factors 58 determining disease severity in pregnancy associated alloimmunizations, resulting in 59 excessive thrombocytopenia''s and blood cell destruction when targeted by afucosylated 60 antibodies (11-13). 109 Analogous to the platelet and Red Blood cell alloantigens (10-12, 18), the response to these 110 enveloped viruses also showed significant afucosylation of the antigen-specific IgG (Fig.2B) , 111 while the afucosylation was absent against the non-enveloped virus Parvo B19 (Fig.2C ). Regulated glycosylation patterns of IgG during alloimmune 405 responses against human platelet antigens abstract: IgG antibodies are crucial for protection against invading pathogens. A highly conserved N-linked glycan within the IgG-Fc-tail, essential for IgG function, shows variable composition in humans. Afucosylated IgG variants are already used in anti-cancer therapeutic antibodies for their elevated binding and killing activity through Fc receptors (FcγRIIIa). Here, we report that afucosylated IgG which are of minor abundance in humans (∼6% of total IgG) are specifically formed against surface epitopes of enveloped viruses after natural infections or immunization with attenuated viruses, while protein subunit immunization does not elicit this low fucose response. This can give beneficial strong responses, but can also go awry, resulting in a cytokine-storm and immune-mediated pathologies. In the case of COVID-19, the critically ill show aggravated afucosylated-IgG responses against the viral spike protein. In contrast, those clearing the infection unaided show higher fucosylation levels of the anti-spike protein IgG. Our findings indicate antibody glycosylation as a potential factor in inflammation and protection in enveloped virus infections including COVID-19. url: https://doi.org/10.1101/2020.05.18.099507 doi: 10.1101/2020.05.18.099507 id: cord-274409-4ugdxbmy author: Laskar, Rezwanuzzaman title: Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India date: 2020-10-19 words: 3300.0 sentences: 190.0 pages: flesch: 57.0 cache: ./cache/cord-274409-4ugdxbmy.txt txt: ./txt/cord-274409-4ugdxbmy.txt summary: title: Mutational analysis and assessment of its impact on proteins of SARS-CoV-2 genomes from India Further, constitution of ''Disease'' mutations in genomes from asymptomatic people was mere 11% but those from deceased patients was over three folds higher at 38% indicating contribution of these mutations to the pathophysiology of the SARS-CoV-2. With a definitive possibility of India becoming the most affected country by SARS-CoV-2 in near future and the demographic burden involved, its pertinent to be analyze the accumulating variations in the genome accounting for possible changes in protein and their potential to alter the virus in any manner. Herein we extend our study using the same congregation of sequences to analyze the nature and composition of the observed mutations and their impact on proteins of SARS-CoV-2. The distribution of Disease and Neutral variants across the different genes of SARS-CoV-2 has been shown in Table 4 and Supplementary file 5. abstract: The ongoing global pandemic of SARS-CoV-2 implies a corresponding accumulation of mutations. Herein the mutational status of 611 genomes from India along with their impact on proteins was ascertained. After excluding gaps and ambiguous sequences, a total of 493 variable sites (152 parsimony informative and 341 singleton) were observed. The most prevalent reference nucleotide was C (209) and substituted one was T (293). NSP3 had the highest incidence of 101 sites followed by S protein (74 sites), NSP12b (43 sites) and ORF3a (31 sites). The average number of mutations per sample for males and females was 2.56 and 2.88 respectively suggesting a higher contribution of mutations from females. Non-uniform geographical distribution of mutations implied by Odisha (30 samples, 109 mutations) and Tamil Nadu (31 samples, 40 mutations) suggests that sequences in some regions are mutating faster than others. There were 281 mutations (198 ‘Neutral’ and 83 ‘Disease’) affecting amino acid sequence. NSP13 has a maximum of 14 ‘Disease’ variants followed by S protein and ORF3a with 13 each. Further, constitution of ‘Disease’ mutations in genomes from asymptomatic people was mere 11% but those from deceased patients was over three folds higher at 38% indicating contribution of these mutations to the pathophysiology of the SARS-CoV-2. url: https://doi.org/10.1101/2020.10.19.345066 doi: 10.1101/2020.10.19.345066 id: cord-102324-tu804znm author: Le Sage, Valerie title: Pre-existing immunity provides a barrier to airborne transmission of influenza viruses date: 2020-06-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Human-to-human transmission of influenza viruses is a serious public health threat, yet the precise role of immunity from previous infections on the susceptibility to airborne viruses is still unknown. Using human seasonal influenza viruses in a ferret model, we examined the roles of exposure duration and heterosubtypic immunity on influenza transmission. We found that airborne transmission of seasonal influenza strains is abrogated in recipient animals with pre-existing non-neutralizing immunity, indicating that transmissibility of a given influenza virus strain should be examined in the context of ferrets that are not immunologically naïve. url: https://doi.org/10.1101/2020.06.15.103747 doi: 10.1101/2020.06.15.103747 id: cord-349794-mhviub6e author: Le, Brian L. title: Transcriptomics-based drug repositioning pipeline identifies therapeutic candidates for COVID-19 date: 2020-10-23 words: 3810.0 sentences: 216.0 pages: flesch: 43.0 cache: ./cache/cord-349794-mhviub6e.txt txt: ./txt/cord-349794-mhviub6e.txt summary: We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. By infecting human adenocarcinomic alveolar basal epithelial cells with SARS-CoV-2 and comparing to controls, the authors generated a list of 120 differentially expressed genes. Here, we applied our existing computational drug repositioning pipeline to identify drug profiles with significantly reversed differential gene expression compared to predicted inhibitors (including one tested in Calu-3) were incubated with SARS-CoV-2 infected human embryonic kidney 293T cells overexpressing ACE2 (293T-ACE2) with viral replication determined using an immunofluorescence-based assay. In this study, we applied our drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available RNA-seq data ( Figure 1 ). Here, we used a transcriptomics-based drug repositioning pipeline to predict therapeutic drug hits for three different input SARS-CoV-2 signatures, each of which came from distinct human cell or tissue origins. abstract: The novel SARS-CoV-2 virus emerged in December 2019 and has few effective treatments. We applied a computational drug repositioning pipeline to SARS-CoV-2 differential gene expression signatures derived from publicly available data. We utilized three independent published studies to acquire or generate lists of differentially expressed genes between control and SARS-CoV-2-infected samples. Using a rank-based pattern matching strategy based on the Kolmogorov-Smirnov Statistic, the signatures were queried against drug profiles from Connectivity Map (CMap). We validated sixteen of our top predicted hits in live SARS-CoV-2 antiviral assays in either Calu-3 or 293T-ACE2 cells. Validation experiments in human cell lines showed that 11 of the 16 compounds tested to date (including clofazimine, haloperidol and others) had measurable antiviral activity against SARS-CoV-2. These initial results are encouraging as we continue to work towards a further analysis of these predicted drugs as potential therapeutics for the treatment of COVID-19. url: https://doi.org/10.1101/2020.10.23.352666 doi: 10.1101/2020.10.23.352666 id: cord-102588-vpu5w9wh author: Le, Trang T. title: treeheatr: an R package for interpretable decision tree visualizations date: 2020-07-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Summary treeheatr is an R package for creating interpretable decision tree visualizations with the data represented as a heatmap at the tree’s leaf nodes. The integrated presentation of the tree structure along with an overview of the data efficiently illustrates how the tree nodes split up the feature space and how well the tree model performs. This visualization can also be examined in depth to uncover the correlation structure in the data and importance of each feature in predicting the outcome. Implemented in an easily installed package with a detailed vignette, treeheatr can be a useful teaching tool to enhance students’ understanding of a simple decision tree model before diving into more complex tree-based machine learning methods. Availability The treeheatr package is freely available under the permissive MIT license at https://trang1618.github.io/treeheatr and https://cran.r-project.org/package=treeheatr. It comes with a detailed vignette that is automatically built with GitHub Actions continuous integration. Contact ttle@pennmedicine.upenn.edu url: https://doi.org/10.1101/2020.07.10.196352 doi: 10.1101/2020.07.10.196352 id: cord-255069-9xueqdri author: Leary, Shay title: Three adjacent nucleotide changes spanning two residues in SARS-CoV-2 nucleoprotein: possible homologous recombination from the transcription-regulating sequence date: 2020-04-11 words: 1821.0 sentences: 77.0 pages: flesch: 43.0 cache: ./cache/cord-255069-9xueqdri.txt txt: ./txt/cord-255069-9xueqdri.txt summary: The findings suggest that homologous recombination may have occurred since its introduction into humans and be a mechanism for increased viral fitness and adaptation of SARS-CoV-2 to human populations. Evidence of viral adaptation to selective pressures as it spreads among diverse human populations has implications for the ongoing potential for changes in viral fitness over time, which in turn may impact transmissibility, disease pathogenesis and immunogenicity. Here we describe a new emerging strain of SARS-CoV-2 within the LGG clade that appears to be the result of a homologous recombination event that introduced three adjacent nucleotide changes spanning two residues of the nucleocapsid protein. Evidence for such adaptations with closely linked compensatory mutations are known to occur under host immune pressure as is well established for other adaptable RNA viruses such as HIV 1,2 and Hepatitis C virus (HCV) 3 . abstract: The COVID-19 pandemic is caused by the single-stranded RNA virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a virus of zoonotic origin that was first detected in Wuhan, China in December 2019. There is evidence that homologous recombination contributed to this cross-species transmission. Since that time the virus has demonstrated a high propensity for human-to-human transmission. Here we report two newly identified adjacent amino acid polymorphisms in the nucleocapsid at positions 203 and 204 (R203K/G204R) due to three adjacent nucleotide changes across the two codons (i.e. AGG GGA to AAA CGA). This new strain within the LGG clade may have arisen by a form of homologous recombination from the core sequence (CS-B) of the transcription-regulating sequences of SAS-CoV-2 itself and has rapidly increased to approximately one third of reported sequences from Europe during the month of March 2020. We note that these polymorphisms are predicted to reduce the binding of an overlying putative HLA-C*07-restricted epitope and that HLA-C*07 is prevalent in Caucasians being carried by >40% of the population. The findings suggest that homologous recombination may have occurred since its introduction into humans and be a mechanism for increased viral fitness and adaptation of SARS-CoV-2 to human populations. url: https://doi.org/10.1101/2020.04.10.029454 doi: 10.1101/2020.04.10.029454 id: cord-293826-2p7dqacd author: Lee, Cheryl Yi-Pin title: Neutralizing antibodies from early cases of SARS-CoV-2 infection offer cross-protection against the SARS-CoV-2 D614G variant date: 2020-10-09 words: 1314.0 sentences: 84.0 pages: flesch: 54.0 cache: ./cache/cord-293826-2p7dqacd.txt txt: ./txt/cord-293826-2p7dqacd.txt summary: Given that a majority of the developing antibody-mediated therapies 68 and serological assays are based on the S antigen of the original Wuhan reference 69 sequence, it is crucial to determine if humoral immunity acquired from the original 70 SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against 71 the novel prevailing D614G variant. Given that a majority of the developing antibody-mediated therapies 68 and serological assays are based on the S antigen of the original Wuhan reference 69 sequence, it is crucial to determine if humoral immunity acquired from the original 70 SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against 71 the novel prevailing D614G variant. Overall, our study shows that the D614G mutation on the S protein does not 150 impact SARS-CoV-2 neutralization by the host antibody response, nor confer viral 151 resistance against the humoral immunity. abstract: The emergence of a SARS-CoV-2 variant with a point mutation in the spike (S) protein, D614G, has taken precedence over the original Wuhan isolate by May 2020. With an increased infection and transmission rate, it is imperative to determine whether antibodies induced against the D614 isolate may cross-neutralize against the G614 variant. In this report, profiling of the anti-SARS-CoV-2 humoral immunity reveals similar neutralization profiles against both S protein variants, albeit waning neutralizing antibody capacity at the later phase of infection. These findings provide further insights towards the validity of current immune-based interventions. IMPORTANCE Random mutations in the viral genome is a naturally occurring event that may lead to enhanced viral fitness and immunological resistance, while heavily impacting the validity of licensed therapeutics. A single point mutation from aspartic acid (D) to glycine (G) at position 614 of the SARS-CoV-2 spike (S) protein, termed D614G, has garnered global attention due to the observed increase in transmissibility and infection rate. Given that a majority of the developing antibody-mediated therapies and serological assays are based on the S antigen of the original Wuhan reference sequence, it is crucial to determine if humoral immunity acquired from the original SARS-CoV-2 isolate is able to induce cross-detection and cross-protection against the novel prevailing D614G variant. url: https://doi.org/10.1101/2020.10.08.332544 doi: 10.1101/2020.10.08.332544 id: cord-258360-fqrn02lr author: Lee, Jimmy title: No evidence of coronaviruses or other potentially zoonotic viruses in Sunda pangolins (Manis javanica) entering the wildlife trade via Malaysia date: 2020-06-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The legal and illegal trade in wildlife for food, medicine and other products is a globally significant threat to biodiversity that is also responsible for the emergence of pathogens that threaten human and livestock health and our global economy. Trade in wildlife likely played a role in the origin of COVID-19, and viruses closely related to SARS-CoV-2 have been identified in bats and pangolins, both traded widely. To investigate the possible role of pangolins as a source of potential zoonoses, we collected throat and rectal swabs from 334 Sunda pangolins (Manis javanica) confiscated in Peninsular Malaysia and Sabah between August 2009 and March 2019. Total nucleic acid was extracted for viral molecular screening using conventional PCR protocols used to routinely identify known and novel viruses in extensive prior sampling (>50,000 mammals). No sample yielded a positive PCR result for any of the targeted viral families – Coronaviridae, Filoviridae, Flaviviridae, Orthomyxoviridae and Paramyxoviridae. In light of recent reports of coronaviruses including a SARS-CoV-2 related virus in Sunda pangolins in China, the lack of any coronavirus detection in our ‘upstream’ market chain samples suggests that these detections in ‘downstream’ animals more plausibly reflect exposure to infected humans, wildlife or other animals within the wildlife trade network. While confirmatory serologic studies are needed, it is likely that Sunda pangolins are incidental hosts of coronaviruses. Our findings further support the importance of ending the trade in wildlife globally. url: https://doi.org/10.1101/2020.06.19.158717 doi: 10.1101/2020.06.19.158717 id: cord-341502-jlzufa28 author: Lee, Sungyul title: The SARS-CoV-2 RNA interactome date: 2020-11-02 words: 5845.0 sentences: 362.0 pages: flesch: 51.0 cache: ./cache/cord-341502-jlzufa28.txt txt: ./txt/cord-341502-jlzufa28.txt summary: The second pool of 275 oligos ("Probe II") covers the remaining region (21563:29872, NC_045512.2) which is shared by both the gRNA and sgRNAs. To first check whether our method specifically captures the viral RNP complexes, we compared the resulting purification from Vero cells infected with SARS-CoV-2 (BetaCoV/Korea/KCDC03/2020) at MOI 0.1 for 24 hours (Kim et al., 2020b ) by either Probe I or Probe II. In combination, we define these 109 proteins as the "SARS-CoV-2 RNA interactome." 37 host proteins such as CSDE1 (Unr), EIF4H, FUBP3, G3BP2, PABPC1, ZC3HAV1 were enriched in both the Probe I and Probe II RNP capture experiments on infected cells ( Figure 1F ), thus identifying a robust set of the "core SARS-CoV-2 RNA interactome." Gene ontology (GO) term enrichment analysis revealed that these host factors are involved in RNA stability control, mRNA function, and viral process ( Figure S1F ). To measure the impact of these host proteins on coronavirus RNAs, we conducted knockdown experiments and infected Calu-3 cells with SARS-CoV-2 ( Figure 5A and 5B). abstract: SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its ability to repurpose host RNA-binding proteins (RBPs) to form its own RNA interactome. Here, we developed and applied a robust ribonucleoprotein capture protocol to uncover the SARS-CoV-2 RNA interactome. We report 109 host factors that directly bind to SARS-CoV-2 RNAs including general antiviral factors such as ZC3HAV1, TRIM25, and PARP12. Applying RNP capture on another coronavirus HCoV-OC43 revealed evolutionarily conserved interactions between viral RNAs and host proteins. Network and transcriptome analyses delineated antiviral RBPs stimulated by JAK-STAT signaling and proviral RBPs responsible for hijacking multiple steps of the mRNA life cycle. By knockdown experiments, we further found that these viral-RNA-interacting RBPs act against or in favor of SARS-CoV-2. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions. url: https://doi.org/10.1101/2020.11.02.364497 doi: 10.1101/2020.11.02.364497 id: cord-102905-rlee32x7 author: Leis, Jonathan title: Ilaprazole and other novel prazole-based compounds that bind Tsg101 inhibit viral budding of HSV-1/2 and HIV from cells date: 2020-05-04 words: 5755.0 sentences: 297.0 pages: flesch: 51.0 cache: ./cache/cord-102905-rlee32x7.txt txt: ./txt/cord-102905-rlee32x7.txt summary: In this report we show that tenatoprazole and a related prazole drug, ilaprazole, effectively block infectious Herpes Simplex Virus (HSV)-1/2 release from Vero cells in culture. Our results indicate that prazole-based compounds may represent a class of drugs with potential to be broad-spectrum antiviral agents against multiple enveloped viruses, by interrupting cellular Tsg101 interaction with maturing virus, thus blocking the budding process that releases particles from the cell. Tenatoprazole and esomeprazole were shown to quantitatively inhibit the release of infectious HIV-1 from 293T cells in culture, and it was suggested that these effects may be mediated via changes in viral interaction with Tsg101, a key component of the cellular ESCRT complex (5, 33) . Given multiple reports suggesting that herpes viruses also use cellular ESCRT proteins in their replication process (20) (21) (22) (23) we tested if the Tsg101-binding prazole drugs, which blocked budding of HIV-1, would also block the release of herpes viruses from cells. abstract: In many enveloped virus families, including HIV and HSV, a crucial, yet unexploited, step in the viral life cycle is releasing particles from the infected cell membranes. This release process is mediated by host ESCRT complex proteins, which is recruited by viral structural proteins and provides the mechanical means for membrane scission and subsequent viral budding. The prazole drug, tenatoprazole, was previously shown to bind to ESCRT complex member Tsg101 and quantitatively block the release of infectious HIV-1 from cells in culture. In this report we show that tenatoprazole and a related prazole drug, ilaprazole, effectively block infectious Herpes Simplex Virus (HSV)-1/2 release from Vero cells in culture. By electron microscopy, we found that both prazole drugs block the release of HSV particles from the cell nuclear membrane resulting in their accumulation in the nucleus. Ilaprazole also quantitatively blocks the release of HIV-1 from 293T cells with an EC50 of 0.8 μM, which is more potent than tenatoprazole. Finally, we synthesized and tested multiple novel prazole-based analogs that demonstrate both binding to Tsg101 and inhibition of viral egress in the nanomolar range of HIV-1 from 293T cells. Our results indicate that prazole-based compounds may represent a class of drugs with potential to be broad-spectrum antiviral agents against multiple enveloped viruses, by interrupting cellular Tsg101 interaction with maturing virus, thus blocking the budding process that releases particles from the cell. Importance These results provide the basis for the development of drugs that target enveloped virus budding that can be used ultimately to control multiple virus infections in humans. url: https://doi.org/10.1101/2020.05.04.075036 doi: 10.1101/2020.05.04.075036 id: cord-285592-0in22wzv author: Lemoine, Frédéric title: COVID-Align: Accurate online alignment of hCoV-19 genomes using a profile HMM date: 2020-05-25 words: 3755.0 sentences: 262.0 pages: flesch: 64.0 cache: ./cache/cord-285592-0in22wzv.txt txt: ./txt/cord-285592-0in22wzv.txt summary: Moreover, COVID-Align provides summary statistics, which can be used to determine the sequencing quality and evolutionary novelty of input genomes (e.g. number of new mutations and indels). Unique mutations and indels are possibly due to errors (sequencing, assembly etc.), while new ones (seen at least twice in submitted genomes, for the first time) likely correspond to evolutionary novelties (see Sup. Info. Right: Statistics summary, displaying the number of High and Low Quality genomes, and the number of evolutionary events (mutations, gaps, gap openings, insertions, insertion openings). For each of the input genomes, COVID-Align computes a series of summary statistics to help users analyze their data, remove problematic sequences, and detect those containing evolutionary novelties. When new sequences with confirmed insertions and deletions will be available from emerging genomes, they will be incorporated in the profile and the resulting MSA will closely account for these indels. abstract: Motivation The first cases of the COVID-19 pandemic emerged in December 2019. Until the end of February 2020, the number of available genomes was below 1,000, and their multiple alignment was easily achieved using standard approaches. Subsequently, the availability of genomes has grown dramatically. Moreover, some genomes are of low quality with sequencing/assembly errors, making accurate re-alignment of all genomes nearly impossible on a daily basis. A more efficient, yet accurate approach was clearly required to pursue all subsequent bioinformatics analyses of this crucial data. Results hCoV-19 genomes are highly conserved, with very few indels and no recombination. This makes the profile HMM approach particularly well suited to align new genomes, add them to an existing alignment and filter problematic ones. Using a core of ∼2,500 high quality genomes, we estimated a profile using HMMER, and implemented this profile in COVID-Align, a user-friendly interface to be used online or as standalone via Docker. The alignment of 1,000 genomes requires less than 20mn on our cluster. Moreover, COVID-Align provides summary statistics, which can be used to determine the sequencing quality and evolutionary novelty of input genomes (e.g. number of new mutations and indels). Availability https://covalign.pasteur.cloud, hub.docker.com/r/evolbioinfo/covid-align Contacts olivier.gascuel@pasteur.fr, frederic.lemoine@pasteur.fr Supplementary information Supplementary information is available at Bioinformatics online. url: https://doi.org/10.1101/2020.05.25.114884 doi: 10.1101/2020.05.25.114884 id: cord-324888-oak27okj author: Leng, Ling title: Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis date: 2020-04-18 words: 2814.0 sentences: 155.0 pages: flesch: 46.0 cache: ./cache/cord-324888-oak27okj.txt txt: ./txt/cord-324888-oak27okj.txt summary: title: Potential microenvironment of SARS-CoV-2 infection in airway epithelial cells revealed by Human Protein Atlas database analysis Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. Therefore, we wonder whether there are some key local microenvironment proteins specifically expressed on the surface of airway EpC that makes the virus prefer airway EpCs. In some cases, additional cell surface molecules or co-receptors are required for sufficient viral entry into host cells. We used the human protein atlas (HPA) database [16] to extract the protein expression level of 65 receptors involved in "virus receptor activity" (GO:0001618) of EpCs and epithelial or epithelial-derived cells from 14 organs (16 cell types) ( Figure 1A and Supplementary Materials and Methods). abstract: The outbreak of COVID-19 has caused serious epidemic events in China and other countries. With the rapid spread of COVID-19, it is urgent to explore the pathogenesis of this novel coronavirus. However, the foundational research of COVID-19 is very weak. Although angiotensin converting enzyme 2 (ACE2) is the reported receptor of SARS-CoV-2, information about SARS-CoV-2 invading airway epithelial cells is very limited. Based on the analysis of the Human Protein Atlas database, we compared the virus-related receptors of epithelial-derived cells from different organs and found potential key molecules in the local microenvironment for SARS-CoV-2 entering airway epithelial cells. In addition, we found that these proteins were associated with virus reactive proteins in host airway epithelial cells, which may promote the activation of the immune system and the release of inflammatory factors. Our findings provide a new research direction for understanding the potential microenvironment required by SARS-CoV-2 infection in airway epithelial, which may assist in the discovery of potential drug targets against SARS-CoV-2 infection. url: https://doi.org/10.1101/2020.04.16.045799 doi: 10.1101/2020.04.16.045799 id: cord-103733-blam1f4c author: Levade, Inès title: Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study date: 2020-06-24 words: 2663.0 sentences: 145.0 pages: flesch: 41.0 cache: ./cache/cord-103733-blam1f4c.txt txt: ./txt/cord-103733-blam1f4c.txt summary: title: Predicting Vibrio cholerae infection and disease severity using metagenomics in a prospective cohort study cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera. Conclusion Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera. SUMMARY Cholera infection and disease severity can be predicted using metagenomic sequencing of the gut microbiome pre-infection in a prospective cohort, and suggests potentially protective bacterial species and genes. Our metagenomic analysis yielded improved 85 outcome predictions compared to 16S rRNA sequencing, and identified bacterial genes 86 associated with remaining uninfected after exposure to V. Applied to the Midani 230 2018 cohort, this model predicted outcomes significantly better than random (shuffled labels) 231 using species, strains or pathway data, but not gene families ( Table 1 ; see Table S3 for p-232 values). abstract: Background Susceptibility to Vibrio cholerae infection is impacted by blood group, age, and pre-existing immunity, but these factors only partially explain who becomes infected. A recent study used 16S rRNA amplicon sequencing to quantify the composition of the gut microbiome and identify predictive biomarkers of infection with limited taxonomic resolution. Methods To achieve increased resolution of gut microbial factors associated with V. cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera. Results Using machine learning, we resolved species, strains, gene families, and cellular pathways in the microbiome at the time of exposure to V. cholerae to identify markers that predict infection and symptoms. Use of metagenomic features improved the precision and accuracy of prediction relative to 16S sequencing. We also predicted disease severity, although with greater uncertainty than our infection prediction. Species within the genera Prevotella and Bifidobacterium predicted protection from infection, and genes involved in iron metabolism also correlated with protection. Conclusion Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera. SUMMARY Cholera infection and disease severity can be predicted using metagenomic sequencing of the gut microbiome pre-infection in a prospective cohort, and suggests potentially protective bacterial species and genes. url: https://doi.org/10.1101/2020.02.25.960930 doi: 10.1101/2020.02.25.960930 id: cord-342010-5mkf67os author: Levasseur, Anthony title: Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients date: 2020-09-04 words: 5348.0 sentences: 975.0 pages: flesch: 103.0 cache: ./cache/cord-342010-5mkf67os.txt txt: ./txt/cord-342010-5mkf67os.txt summary: title: Genomic diversity and evolution of coronavirus (SARS-CoV-2) in France from 309 COVID-19-infected patients cord_uid: 5mkf67os The evolution and mutational events of the SARS-CoV-2 genomes are critical for controlling virulence, transmissibility, infectivity, severity of symptoms and mortality associated to this infectious disease. We collected and investigated 309 SARS-CoV-2 genomes from patients infected in France. Detailed genome cartography of all mutational events (SNPs, indels) was reported and correlated to clinical features of patients. A comparative analysis between our 309 SARS-CoV-2 genomes from French patients and the reference Wuhan coronavirus genome revealed 315 substitution mutations and six deletion events: ten were in 5''/3'' UTR, 178 were nonsynonymous, 126 were synonymous and one generated a stop codon. Clinical outcomes of the 309 COVID-19-infected patients were investigated according to the mutational signatures of viral variants. Inclusion of the French cohort enabled us to identify 161 novel mutations never reported in SARS-CoV-2 genomes collected worldwide. abstract: The novel coronavirus (SARS-CoV-2) causes pandemic of viral pneumonia. The evolution and mutational events of the SARS-CoV-2 genomes are critical for controlling virulence, transmissibility, infectivity, severity of symptoms and mortality associated to this infectious disease. We collected and investigated 309 SARS-CoV-2 genomes from patients infected in France. Detailed genome cartography of all mutational events (SNPs, indels) was reported and correlated to clinical features of patients. A comparative analysis between our 309 SARS-CoV-2 genomes from French patients and the reference Wuhan coronavirus genome revealed 315 substitution mutations and six deletion events: ten were in 5’/3’ UTR, 178 were nonsynonymous, 126 were synonymous and one generated a stop codon. Six different deleted areas were also identified in nine viral variants. In particular, 30 substitution mutations (18 nonsynonymous) and one deletion (Δ21765-21770) concerned the spike S glycoprotein. An average of 7.8 mutational events (+/- 1.7 SD) and a median of 8 (range, 7-9) were reported per viral isolate. Comparative analyses and clustering of specific mutational signatures in 309 genomes disclose several divisions in groups and subgroups combining their geographical and phylogenetic origin. Clinical outcomes of the 309 COVID-19-infected patients were investigated according to the mutational signatures of viral variants. These findings highlight the genome dynamics of the coronavirus 2019-20 and shed light on the mutational landscape and evolution of this virus. Inclusion of the French cohort enabled us to identify 161 novel mutations never reported in SARS-CoV-2 genomes collected worldwide. These results support a global and continuing surveillance of the emerging variants of the coronavirus SARS-CoV-2. url: https://doi.org/10.1101/2020.09.04.282616 doi: 10.1101/2020.09.04.282616 id: cord-104008-luqvw0y8 author: Levinson, Julia title: Investigating the effectiveness of school health services delivered by a health provider: a systematic review of systematic reviews date: 2019-02-07 words: 6729.0 sentences: 337.0 pages: flesch: 50.0 cache: ./cache/cord-104008-luqvw0y8.txt txt: ./txt/cord-104008-luqvw0y8.txt summary: Systematic reviews of intervention studies that evaluated school-based or school-linked 31 health services delivered by a health provider were included. Systematic reviews of intervention studies that evaluated school-based or school-linked 31 health services delivered by a health provider were included. Through a comprehensive literature search, the 71 overview aimed to identify health areas and specific school health service interventions that 72 have at least some evidence of effectiveness. Finally, 74 the overview aimed to identify the health areas and specific school health services 75 interventions for which no SRs were found, whether because the primary literature does not 76 exist or where there are primary studies but no SR has been conducted. It is difficult to determine overall effectiveness of school health services from this overview because the included SRs do not sufficiently cover the health areas most relevant for children and adolescents. abstract: Schools are the only institution regularly reaching the majority of school-age children and adolescents across the globe. Although at least 102 countries have school health services, there is no rigorous, evidence-based guidance on which school health services are effective and should be implemented in schools. To investigate the effectiveness of school health services for improving the health of school-age children and adolescents, a systematic review of systematic reviews (overview) was conducted. Five databases were searched through June 2018. Systematic reviews of intervention studies that evaluated school-based or school-linked health services delivered by a health provider were included. Review quality was assessed using a modified Ballard and Montgomery four-item checklist. 1654 references were screened and 20 systematic reviews containing 270 primary studies were assessed narratively. Interventions with evidence for effectiveness addressed autism, depression, anxiety, obesity, dental caries, visual acuity, asthma, and sleep. No review evaluated the effectiveness of a multi-component school health services intervention addressing multiple health areas. Strongest evidence supports implementation of anxiety prevention programs, indicated asthma education, and vision screening with provision of free spectacles. Additional systematic reviews are needed that analyze the effectiveness of comprehensive school health services, and specific services for under-researched health areas relevant for this population. url: https://doi.org/10.1101/543868 doi: 10.1101/543868 id: cord-102835-71ome9h8 author: Levinson, Maxwell Adam title: FAIRSCAPE: A Framework for FAIR and Reproducible Biomedical Analytics date: 2020-08-15 words: 4772.0 sentences: 288.0 pages: flesch: 51.0 cache: ./cache/cord-102835-71ome9h8.txt txt: ./txt/cord-102835-71ome9h8.txt summary: All results are annotated with FAIR metadata using the evidence graph model for access, validation, reproducibility, and re-use of archived data and software. We set out to construct a provenance-aware computational data lake, as described above, by significantly extending and refactoring the identifier and metadata services framework we and our colleagues developed in the NIH Data Commons Pilot Project Consortium (Timothy Clark et al. We extended and re-engineered this framework over time to track and visualize computations and their evidence, to manage the computational objects (such as data and software) as well as their metadata, to analyze very large datasets with horizontal scale-out, to support neuroimaging workflows, and to make it generally more easy for scientists and computational analysts to use, by providing Binder and Notebook services (Jupyter et al. It supports transparent disclosure of the Evidence Graphs of computed results, with access to the persistent identifiers of the cited data or software, and to their stored metadata. abstract: Results of computational analyses require transparent disclosure of their supporting resources, while the analyses themselves often can be very large scale and involve multiple processing steps separated in time. Evidence for the correctness of any analysis consists of accessible data and software with runtime parameters, environment, and personnel involved. Evidence graphs - a derivation of argumentation frameworks adapted to biological science - can provide this disclosure as machine-readable metadata resolvable from persistent identifiers for computationally generated graphs, images, or tables, that can be archived and cited in a publication including a persistent ID. We have built a cloud-based, computational research commons for predictive analytics on biomedical time series datasets with hundreds of algorithms and thousands of computations using a reusable computational framework we call FAIRSCAPE. FAIRSCAPE computes a complete chain of evidence on every result, including software, computations, and datasets. An ontology for Evidence Graphs, EVI (https://w3id.org/EVI), supports inferential reasoning over the evidence. FAIRSCAPE can run nested or disjoint workflows and preserves the provenance graph across them. It can run Apache Spark jobs, scripts, workflows, or user-supplied containers. All objects are assigned persistent IDs, including software. All results are annotated with FAIR metadata using the evidence graph model for access, validation, reproducibility, and re-use of archived data and software. FAIRSCAPE is a reusable computational framework, enabling simplified access to modern scalable cloud-based components. It fully implements the FAIR data principles and extends them to provide FAIR Evidence, including provenance of datasets, software and computations, as metadata for all computed results. url: https://doi.org/10.1101/2020.08.10.244947 doi: 10.1101/2020.08.10.244947 id: cord-325124-0hxan9rw author: Li, Chenyu title: Highly sensitive and full-genome interrogation of SARS-CoV-2 using multiplexed PCR enrichment followed by next-generation sequencing date: 2020-05-18 words: 6119.0 sentences: 364.0 pages: flesch: 53.0 cache: ./cache/cord-325124-0hxan9rw.txt txt: ./txt/cord-325124-0hxan9rw.txt summary: However, it has been reported that only 47-59% of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites. With the goal of improving sensitivity and accommodating various application settings, we developed a multiplex-PCR-based method comprised of 343 pairs of specific primers, and demonstrated its efficiency to detect SARS-CoV-2 at low copy numbers. We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purified from 13 COVID-19 positive specimens, and detected mutations through next generation sequencing. Finally, we developed a multiplex-PCR-based metagenomic method in parallel, that required modest sequencing depth for uncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates. To overcome this constraint, we developed a multiplex-PCR-based metagenomic method that achieved >96% coverage of the S and N genes of SARS-CoV-2 in the contest of human gDNA, while only required ~0.6M of total reads per library. abstract: Many detection methods have been used or reported for the diagnosis and/or surveillance of COVID-19. Among them, reverse transcription polymerase chain reaction (RT-PCR) is the most commonly used because of its high sensitivity, typically claiming detection of about 5 copies of viruses. However, it has been reported that only 47-59% of the positive cases were identified by some RT-PCR methods, probably due to low viral load, timing of sampling, degradation of virus RNA in the sampling process, or possible mutations spanning the primer binding sites. Therefore, alternative and highly sensitive methods are imperative. With the goal of improving sensitivity and accommodating various application settings, we developed a multiplex-PCR-based method comprised of 343 pairs of specific primers, and demonstrated its efficiency to detect SARS-CoV-2 at low copy numbers. The assay produced clean characteristic target peaks of defined sizes, which allowed for direct identification of positives by electrophoresis. We further amplified the entire SARS-CoV-2 genome from 8 to half a million viral copies purified from 13 COVID-19 positive specimens, and detected mutations through next generation sequencing. Finally, we developed a multiplex-PCR-based metagenomic method in parallel, that required modest sequencing depth for uncovering SARS-CoV-2 mutational diversity and potentially novel or emerging isolates. url: https://doi.org/10.1101/2020.03.12.988246 doi: 10.1101/2020.03.12.988246 id: cord-274528-mr81o9cu author: Li, Fei title: Distinct mechanisms for TMPRSS2 expression explain organ-specific inhibition of SARS-CoV-2 infection by enzalutamide date: 2020-09-12 words: 6428.0 sentences: 416.0 pages: flesch: 53.0 cache: ./cache/cord-274528-mr81o9cu.txt txt: ./txt/cord-274528-mr81o9cu.txt summary: Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Notably, in addition to prostate, other essential 40 organs, including lung, kidney and liver, which are permissive for SARS-CoV-2 infection in human, were 41 characterized with Tmprss2-postive epithelial cells ( Fig. 1b and Extended Data Fig. 1c ). Consistently, 25 enzalutamide significantly decreased TMPRSS2 expression and inhibited SARS-CoV-2 infection in human 26 prostate cancer cells (Fig. 2) . abstract: The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly become a global public health threat due to the lack of effective drugs or vaccines against SARS-CoV-2. The efficacy of several repurposed drugs has been evaluated in clinical trials. Among these drugs, a relatively new antiandrogen agent, enzalutamide, was proposed because it reduces the expression of transmembrane serine protease 2 (TMPRSS2), a key component mediating SARS-CoV-2-driven entry into host cells, in prostate cancer cells. However, definitive evidence for the therapeutic efficacy of enzalutamide in COVID-19 is lacking. Here, we evaluated the antiviral efficacy of enzalutamide in prostate cancer cells, lung cancer cells, human lung organoids and SARS-CoV-2-infected Ad-ACE2-transduced Tmprss2 knockout (Tmprss2-KO) and wild-type (WT) mice. TMPRSS2 knockout significantly inhibited SARS-CoV-2 infection in vivo. Enzalutamide effectively inhibited SARS-CoV-2 infection in human prostate cancer cells (LNCaP) but not in human lung cancer cells or patient-derived lung organoids. Although Tmprss2 knockout effectively blocked SARS-CoV-2 infection in ACE2-transduced mice, enzalutamide showed no antiviral activity due to the AR independence of TMPRSS2 expression in mouse and human lung epithelial cells. Moreover, we observed distinct AR binding patterns between prostate cells and lung cells and a lack of direct binding of AR to TMPRSS2 in human lung cells. Thus, our findings do not support the postulated protective role of enzalutamide in treating COVID-19. url: https://doi.org/10.1101/2020.09.11.293035 doi: 10.1101/2020.09.11.293035 id: cord-294275-pp0vlaye author: Li, Jingjing title: Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow date: 2020-06-03 words: 2367.0 sentences: 152.0 pages: flesch: 55.0 cache: ./cache/cord-294275-pp0vlaye.txt txt: ./txt/cord-294275-pp0vlaye.txt summary: Here, we propose a method to detect SARC-Cov-2 infection within two hours combined with Loop-mediated Isothermal Amplification (LAMP) reaction and nanopore Flongle workflow. Here, we use nanopore Flongle workflow combined with LAMP reaction to propose a faster and more convenient method to detect SARS-CoV-2 and other respiratory viruses in two hours. This study presents a LAMP based method combined with nanopore Flongle rapid realtime sequencing workflow to detect COVID-19 as low as 3.25×10^2 copies/mL of SARS-CoV-2 in both laboratory and wild-caught environment. To test the limit of detection, the amplification products of dilution gradient 3.25×10^4, 3.25 × 10^3, 1.1 × 10^3, 6.5 × 10^2, 3.25 × 10^2 copies/mL and negative control total 12 samples were constructed another barcoding library (Oxford Nanopore, SQK-RBK004) as described above and sequenced using a PromethION flowcell to achieve more data. The study design ( Figure 2 ) for SARS-CoV-2 detection is based on LAMP rapid amplification of specific genes and sequenced by nanopore Flongle workflow. abstract: The ongoing novel coronavirus (COVID-19) outbreak as a global public health emergency infected by SARC-CoV-2 has caused devastating loss around the world. Currently, a lot of diagnosis methods have been used to detect the infection. The nucleic acid (NA) testing is reported to be the clinical standard for COVID-19 infection. Evidence shows that a faster and more convenient method to detect in the early phase will control the spreading of SARS-CoV-2. Here, we propose a method to detect SARC-Cov-2 infection within two hours combined with Loop-mediated Isothermal Amplification (LAMP) reaction and nanopore Flongle workflow. In this approach, RNA reverse transcription and nucleic acid amplification reaction with one step in 30 minutes at 60-65°C constant temperature environment, nanopore Flongle rapidly adapter ligated within 10 minutes. Flongle flow cell sequencing and analysis in real-time. This method described here has the advantages of rapid amplification, convenient operation and real-time detection which is the most important for rapid and reliable clinical diagnosis of COVID-19. Moreover, this approach not only can be used for SARS-CoV-2 detection but also can be extended to other respiratory viruses and pathogens. url: https://doi.org/10.1101/2020.06.03.131474 doi: 10.1101/2020.06.03.131474 id: cord-102184-8u73adnk author: Li, Jinzhi title: Visual input into the Drosophila melanogaster mushroom body date: 2020-05-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ability to integrate input from different sensory systems is a fundamental property of many brains. Yet, the patterns of neuronal connectivity that underlie such multisensory integration remain poorly characterized. The Drosophila melanogaster mushroom body — an associative center required for the formation of olfactory and visual memories — is an ideal system to investigate how different sensory channels converge in higher-order brain centers. The neurons connecting the mushroom body to the olfactory system have been described in great detail, but input from other sensory systems remains poorly defined. Here, we use a range of anatomical and genetic techniques to identify two novel types of mushroom body input neuron that connect visual processing centers — namely the lobula and the posterior lateral protocerebrum — to the dorsal accessory calyx of the mushroom body. Together with previous work that described a pathway conveying visual information from the medulla to the ventral accessory calyx of the mushroom body (Vogt et al., 2016), our study defines a second, parallel pathway that is anatomically poised to convey information from the visual system to the dorsal accessory calyx. This connectivity pattern — the segregation of the visual information into two separate pathways — could be a fundamental feature of the neuronal architecture underlying multisensory integration in associative brain centers. url: https://doi.org/10.1101/2020.02.07.935924 doi: 10.1101/2020.02.07.935924 id: cord-103946-c5i8btp7 author: Li, Maohua title: Next generation of anti-PD-L1 Atezolizumab with better anti-tumor efficacy in vivo date: 2020-07-01 words: 4380.0 sentences: 216.0 pages: flesch: 51.0 cache: ./cache/cord-103946-c5i8btp7.txt txt: ./txt/cord-103946-c5i8btp7.txt summary: Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Based on the structural information acquired from different antibodies in Protein data bank (e.g., PDB ID: 1IGT), we hypothesized that an insertion of a short but very flexible sequence in the hinge region or somewhere upstream of the glycosylation site of N297 may cut off the stress transmission signal between the Fv and Fc domain. Clearly, the insertion of GGGS between G237 and G238 of human IgG1 heavy chain showed no significant negative impact on antibody''s affinity and inhibitory activity. Our data demonstrated that the insertion of GGGS in the hinge regions of human IgG1 could abolish their ADCC activities completely without concering negative impact on antibody affinities, inhibitory activities, expression levels, stabilities or immunogenicity. For those well-known antibody drugs, such as Genentech''s aglycosylated anti-PD-L1 Atezolizumab, we demonstrated that inserting GGGS in the hinge regions of human IgG1 Fc could remove the ADCC activities completely. abstract: Some cancer patients treated with Atezolizumab, PD-L1 antibody drug launched by Genentech, quickly developed anti-drug antibody (ADA), led to loss of efficacy. This was likely due to the heavy aggregation of Atezolizumab, caused by mutation of N297A for removing unwanted antibody-dependent cytotoxicity (ADCC) of IgG1 antibody drug. Here, we developed a new version of Atezolizumab (Maxatezo), which was demonstrated better anti-tumor efficacy in vivo. In Atezolizumab, we mutated 297A to 297N back to bring back the glycosylation, and inserted a short sequence GGGS between G237 and G238 in the hinge region of the IgG1 heavy chain. Our data shown that insertion of GGGS, without altering the anti-PD-L1 antibody affinity and inhibitory activity, completely abolished the ADCC activity, as same as Atezolizumab. Moreover, the insertion of GGGS, without altering the glycosylation profile of IgG1, increased the yields of anti-PD-L1 antibody considerately. Additionally, glycosylation improved the stability yet reduced the amounts of aggregations in the antibody solutions. In turn, the level of ADA in animals treated with Maxatezo was 70% lower than the ones treated with Atezolizumab. Most importantly, at the same 10mg/kg dose, the anti-tumor activity of Maxatezo had attained 98% compared to that of Atezolizumab at 68%. url: https://doi.org/10.1101/2020.06.30.166207 doi: 10.1101/2020.06.30.166207 id: cord-326882-bbn1tfq5 author: Li, Quan title: Genetic Variability of Human Angiotensin-Converting Enzyme 2 (hACE2) Among Various Ethnic Populations date: 2020-04-14 words: 1675.0 sentences: 104.0 pages: flesch: 55.0 cache: ./cache/cord-326882-bbn1tfq5.txt txt: ./txt/cord-326882-bbn1tfq5.txt summary: We set out to examine genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARSCoV-2. To explore the variability in genetic polymorphisms and expression in human ACE2 (hACE2), we set out to determine if there were any differences between the Asian and Caucasian populations for ACE2 polymorphisms and compare the variability of hACE2 expression in peripheral blood among eight different populations. In order to investigate whether differences in genetic variations exist between Caucasians and Asians and if these variants can influence the efficiency of cell entry of SARS-CoV-2, we retrieved the variants in the hACE2 from gnomAD v2.1 exomes13. Asians and Other Races Express Similar Levels of and Share the Same Genetic Polymorphisms of the SARS-CoV-2 Cell-Entry Receptor abstract: There appears to be large regional variations for susceptibility, severity and mortality for Covid-19 infections. We set out to examine genetic differences in the human angiotensin-converting enzyme 2 (hACE2) gene, as its receptor serves as a cellular entry for SARS- CoV-2. By comparing 56,885 Non-Finnish European and 9,197 East Asians (including 1,909 Koreans) four missense mutations were noted in the hACE2 gene. Molecular dynamic demonstrated that two of these variants (K26R and I468V) may affect binding characteristics between S protein of the virus and hACE2 receptor. We also examined hACE2 gene expression in eight global populations from the HapMap3 and noted marginal differences in expression for some populations as compared to the Chinese population. However, for both of our studies, the magnitude of the difference was small and the significance is not clear in the absence of further in vitro and functional studies. url: https://doi.org/10.1101/2020.04.14.041434 doi: 10.1101/2020.04.14.041434 id: cord-332134-88wfcc3y author: Li, Tingting title: A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection date: 2020-09-24 words: 2051.0 sentences: 158.0 pages: flesch: 57.0 cache: ./cache/cord-332134-88wfcc3y.txt txt: ./txt/cord-332134-88wfcc3y.txt summary: title: A potent synthetic nanobody targets RBD and protects mice from SARS-CoV-2 infection Molecular mechanism for neutralization 157 Structure alignment of SR4-, MR17-and ACE2-RBD 4 showed that both sybodies 158 engage with RBD at the receptor-binding motif (RBM) ( Fig. 2A, 2B) . Taken together, SR4 169 and MR17, and probably MR3, neutralize SARS-CoV-2 by competitively blocking the For biparatopic fusion, we first identified two sybodies, namely LR1 and LR5 (Fig. 208 3A, 3B), that could bind RBD in addition to MR3 using the BLI assay. As LR5 showed 209 higher affinity and neutralization activity than LR1 (Fig. 1A) , we fused this non-210 competing sybody to the N-terminal of MR3 with various length of GS linkers ranging 211 from 13 to 34 amino acids (Extended Data Table S1 ). Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with 803 abstract: SARS-CoV-2, the causative agent of COVID-191, recognizes host cells by attaching its receptor-binding domain (RBD) to the host receptor ACE22–7. Neutralizing antibodies that block RBD-ACE2 interaction have been a major focus for therapeutic development8–18. Llama-derived single-domain antibodies (nanobodies, ∼15 kDa) offer advantages including ease of production and possibility for direct delivery to the lungs by nebulization19, which are attractive features for bio-drugs against the global respiratory disease. Here, we generated 99 synthetic nanobodies (sybodies) by in vitro selection using three libraries. The best sybody, MR3 bound to RBD with high affinity (KD = 1.0 nM) and showed high neutralization activity against SARS-CoV-2 pseudoviruses (IC50 = 0.40 μg mL−1). Structural, biochemical, and biological characterization of sybodies suggest a common neutralizing mechanism, in which the RBD-ACE2 interaction is competitively inhibited by sybodies. Various forms of sybodies with improved potency were generated by structure-based design, biparatopic construction, and divalent engineering. Among these, a divalent MR3 conjugated with the albumin-binding domain for prolonged half-life displayed highest potency (IC50 = 12 ng mL−1) and protected mice from live SARS-CoV-2 challenge. Our results pave the way to the development of therapeutic nanobodies against COVID-19 and present a strategy for rapid responses for future outbreaks. url: https://doi.org/10.1101/2020.06.09.143438 doi: 10.1101/2020.06.09.143438 id: cord-264051-ps0x2es1 author: Li, Wei title: Human Identical Sequences of SARS-CoV-2 Promote Clinical Progression of COVID-19 by Upregulating Hyaluronan via NamiRNA-Enhancer Network date: 2020-11-05 words: 8939.0 sentences: 450.0 pages: flesch: 51.0 cache: ./cache/cord-264051-ps0x2es1.txt txt: ./txt/cord-264051-ps0x2es1.txt summary: Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Besides, these virus fragments containing HIS can increase the H3K27 acetylation (H3K27ac) enrichment at their corresponding regions of the human genome in different mammalian cells and activate the expression of adjacent and distant genes associated with inflammation. Collectively, we identified HIS in SARS-CoV-2 genome, and the targeted human genome loci enriched with cytokines genes suggested that HIS may underly the clinical characteristics of COVID-19 patients and serve as a vital player in the pathological progression. abstract: The COVID-19 pandemic is a widespread and deadly public health crisis. The pathogen SARS-CoV-2 replicates in the lower respiratory tract and causes fatal pneumonia. Although tremendous efforts have been put into investigating the pathogeny of SARS-CoV-2, the underlying mechanism of how SARS-CoV-2 interacts with its host is largely unexplored. Here, by comparing the genomic sequences of SARS-CoV-2 and human, we identified five fully conserved elements in SARS-CoV-2 genome, which were termed as “human identical sequences (HIS)”. HIS are also recognized in both SARS-CoV and MERS-CoV genome. Meanwhile, HIS-SARS-CoV-2 are highly conserved in the primate. Mechanically, HIS-SARS-CoV-2, behaving as virus-derived miRNAs, directly target to the human genomic loci and further interact with host enhancers to activate the expression of adjacent and distant genes, including cytokines gene and angiotensin converting enzyme II (ACE2), a well-known cell entry receptor of SARS-CoV-2, and hyaluronan synthase 2 (HAS2), which further increases hyaluronan formation. Noteworthily, hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Our results revealed that unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression. url: https://doi.org/10.1101/2020.11.04.361576 doi: 10.1101/2020.11.04.361576 id: cord-300847-ycuiso0g author: Li, Wei title: Rapid selection of a human monoclonal antibody that potently neutralizes SARS-CoV-2 in two animal models date: 2020-06-02 words: 2801.0 sentences: 172.0 pages: flesch: 55.0 cache: ./cache/cord-300847-ycuiso0g.txt txt: ./txt/cord-300847-ycuiso0g.txt summary: We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. By using phage display we have previously identified a number of potent fully human mAbs (m396, m336, m102.4) against emerging viruses including severe acute respiratory syndrome coronavirus (SARS-CoV) (4) , Middle East respiratory syndrome coronavirus (MERS-CoV) (5) and henipaviruses (6, 7) , respectively, which are also highly effective in animal models of infection (8) (9) (10) (11) ; one of them was administered on a compassionate basis to humans exposed to henipaviruses and successfully evaluated in a clinical trial (12) . Thus, to generate high affinity and safe mAbs we used eight very large (size ~ 10 11 clones each) naive human antibody libraries in Fab, scFv or VH format using PBMCs from 490 individuals total obtained before the SARS-CoV-2 outbreak. abstract: Effective therapies are urgently needed for the SARS-CoV-2/COVID19 pandemic. We identified panels of fully human monoclonal antibodies (mAbs) from eight large phage-displayed Fab, scFv and VH libraries by panning against the receptor binding domain (RBD) of the SARS-CoV-2 spike (S) glycoprotein. One high affinity mAb, IgG1 ab1, specifically neutralized replication competent SARS-CoV-2 with exceptional potency as measured by two different assays. There was no enhancement of pseudovirus infection in cells expressing Fcγ receptors at any concentration. It competed with human angiotensin-converting enzyme 2 (hACE2) for binding to RBD suggesting a competitive mechanism of virus neutralization. IgG1 ab1 potently neutralized mouse ACE2 adapted SARS-CoV-2 in wild type BALB/c mice and native virus in hACE2 expressing transgenic mice. The ab1 sequence has relatively low number of somatic mutations indicating that ab1-like antibodies could be quickly elicited during natural SARS-CoV-2 infection or by RBD-based vaccines. IgG1 ab1 does not have developability liabilities, and thus has potential for therapy and prophylaxis of SARS-CoV-2 infections. The rapid identification (within 6 days) of potent mAbs shows the value of large antibody libraries for response to public health threats from emerging microbes. url: https://www.ncbi.nlm.nih.gov/pubmed/32511413/ doi: 10.1101/2020.05.13.093088 id: cord-252910-7qvnj6c8 author: Li, Xin title: The discovery of a recombinant SARS2-like CoV strain provides insights into SARS and COVID-19 pandemics date: 2020-09-21 words: 4180.0 sentences: 223.0 pages: flesch: 54.0 cache: ./cache/cord-252910-7qvnj6c8.txt txt: ./txt/cord-252910-7qvnj6c8.txt summary: In the present study, we identified key recombination regions and mutation sites cross the SARS-CoV-2, SARS-CoV and SARS-like CoV clusters of betacoronavirus subgroup B. Different from these studies, we previously reported several other findings on SARS-CoV-2 for the first time, including the following in particular: (1) the alternative translation of Nankai coding sequence (CDS) that characterize the rapid mutation rate of betacoronavirus at the nucleotide level [2] ; (2) a furin cleavage site (FCS) "RRAR" in the junction region between S1 and S2 subunits (junction FCS) of SARS-CoV-2 that may increase the efficiency of viral entry into cells [3] ; and (3) the use of 5'' untranslated-region (UTR) barcoding for the detection, identification, classification and phylogenetic analysis of-though not limited to-CoVs [4] . Using the insertions and deletions (InDels) at six sites, we identified two recently detected betacoronavirus strains RmYN01 and RmYN02 from a bat [6] and discovered that RmYN02 was a recombinant SARS2-like CoV strain. abstract: In December 2019, the world awoke to a new zoonotic strain of coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In the present study, we identified key recombination regions and mutation sites cross the SARS-CoV-2, SARS-CoV and SARS-like CoV clusters of betacoronavirus subgroup B. Based on the analysis of these recombination events, we proposed that the Spike protein of SARS-CoV-2 may have more than one specific receptor for its function. In addition, we reported—for the first time—a recombination event of ORF8 at the whole-gene level in a bat and ultimately determined that ORF8 enhances the viral replication. In conjunction with our previous discoveries, we found that receptor binding abilities, junction furin cleavage sites (FCSs), strong first ribosome binding sites (RBSs) and enhanced ORF8s are main factors contributing to transmission, virulence and host adaptability of CoVs. Junction FCSs and enhanced ORF8s increase the efficiencies in viral entry into cells and replication, respectively while strong first RBSs enhance the translational initiation. The strong recombination ability of CoVs integrated these factors to generate multiple recombinant strains, two of which evolved into SARS-CoV and SARS-CoV-2 by nature selection, resulting in the SARS and COVID-19 pandemics. url: https://doi.org/10.1101/2020.07.22.213926 doi: 10.1101/2020.07.22.213926 id: cord-103802-mygo3qx0 author: Li, Yanpeng title: Multiple known and a novel parvovirus associated with an outbreak of feline diarrhea and vomiting date: 2020-03-25 words: 1779.0 sentences: 133.0 pages: flesch: 53.0 cache: ./cache/cord-103802-mygo3qx0.txt txt: ./txt/cord-103802-mygo3qx0.txt summary: title: Multiple known and a novel parvovirus associated with an outbreak of feline diarrhea and vomiting An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and different feline bocaviruses shed by 9/17 cats. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. Shelter 2 a total of 5 individual cats and a sample pool (mixed feces from 3 cats) were Using metagenomics, we found FeBoV1, 2, and 3 and a novel chaphamaparvovirus we named 311 fechavirus in a large fraction of fecal samples and fechavirus in all vomit samples from sick cats 312 in a multi-facility outbreak. Feline Virome-A Review of 409 Novel Enteric Viruses Detected in Cats Feline fecal virome reveals novel and prevalent enteric viruses abstract: An unexplained outbreak of feline diarrhea and vomiting, negative for common enteric viral and bacterial pathogens, was subjected to viral metagenomics and PCR. We characterized from fecal samples the genome of a novel chapparvovirus we named fechavirus that was shed by 8/17 affected cats and different feline bocaviruses shed by 9/17 cats. Also detected were nucleic acids from attenuated vaccine viruses, members of the normal feline virome, viruses found in only one or two cases, and viruses likely derived from ingested food products. Epidemiological investigation of disease signs, time of onset, and transfers of affected cats between three facilities support a possible role for this new chapparvovirus in a highly contagious feline diarrhea and vomiting disease. url: https://doi.org/10.1101/2020.03.24.005876 doi: 10.1101/2020.03.24.005876 id: cord-102454-fqwks0rb author: Liao, Yan Shin J. title: Acid exposure impairs mucus secretion and disrupts mucus transport in neonatal piglet airways date: 2019-06-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Tenacious mucus produced by tracheal and bronchial submucosal glands is a defining feature of cystic fibrosis (CF). Although airway acidification occurs early in CF, whether transient acidification is sufficient to initiate mucus abnormalities is unknown. We studied mucus secretion and mucus transport in piglets forty-eight hours following an intra-airway acid challenge. Acid-challenged piglet airways were distinguished by increased mucin 5B (MUC5B) in the submucosal gland but decreased lung lavage fluid MUC5B, following in vivo cholinergic stimulation, suggesting a failure in submucosal gland secretion. Concomitantly, intrapulmonary airways were obstructed with glycoprotein rich material under both basal and methacholine-stimulated conditions. To mimic a CF-like environment, we also studied mucus secretion and transport under diminished bicarbonate and chloride transport conditions ex vivo. Cholinergic stimulation in acid-challenged piglet airways induced extensive mucus films, greater mucus strand formation, increased dilation of submucosal gland duct openings and decreased mucociliary transport. Finally, to elucidate potential mediators of acid-induced mucus defects, we investigated diminazene aceturate, a small molecule that inhibits the acid-sensing ion channel (ASIC). Diminazene aceturate restored surface MUC5B in acid-challenged piglet airways under basal conditions, mitigated acid-induced airway obstruction, and magnified the number of dilated submucosal gland duct openings. These findings suggest that even transient airway acidification early in life might have profound impacts on mucus secretion and transport properties. Further they highlight diminazene aceturate as an agent that might be beneficial in alleviating certain mucus defects in CF airway disease. One sentence summary Early life airway acidification has profound impacts on mucus secretion and transport. url: https://doi.org/10.1101/669879 doi: 10.1101/669879 id: cord-104036-790vk1cf author: Liekkinen, Juho title: Understanding the Functional Properties of Lipid Heterogeneity in Pulmonary Surfactant Monolayers at the Atomistic Level date: 2020-07-08 words: 6533.0 sentences: 376.0 pages: flesch: 44.0 cache: ./cache/cord-104036-790vk1cf.txt txt: ./txt/cord-104036-790vk1cf.txt summary: In this work, we combined all-atom molecular dynamics simulations, Langmuir trough measurements, and AFM imaging to study synthetic four-component lipid monolayers designed to model protein-free pulmonary surfactant. 22 It has been shown that the pulmonary surfactant monolayers and membranes exhibit phase behaviour that is believed to play roles in lung mechanics; tight packing of lipids with saturated lipid chains promotes its ability to lower surface tension, whereas lipids with unsaturated chains increase pulmonary surfactant fluidity and thus allow for its rapid adsorption to the air-water interface. By using our recently developed protocol for performing simulations of lipid monolayers at the air-water interface, 33, 46 we were able to reach quantitative agreement with experimental surface pressure-area isotherms. Plateau Surface pressure-area isotherm is a key quantity representing monolayer behavior at the water-air interface, and it is readily extracted from both Langmuir trough measurements and computer simulations. abstract: Pulmonary surfactant is a complex mixture of lipids and proteins lining the interior of the alveoli, and constitutes the first barrier to both oxygen and pathogens as they progress toward blood circulation. Despite decades of study, the behavior of the pulmonary surfactant is poorly understood on the molecular scale, which hinders the development of effective surfactant replacement therapies, useful in the treatment of several lung-related diseases. In this work, we combined all-atom molecular dynamics simulations, Langmuir trough measurements, and AFM imaging to study synthetic four-component lipid monolayers designed to model protein-free pulmonary surfactant. We characterized the structural and dynamic properties of the monolayers with a special focus on lateral heterogeneity. Remarkably, simulations reproduce almost quantitatively the experimental data on pressure–area isotherms and the presence of lateral heterogeneities highlighted by AFM. Quite surprisingly, the pressure–area isotherms do not show a plateau region, despite the presence of liquid-condensed nanometer–sized domains at surface pressures larger than 20 mN/m. In the simulations, the domains were small and transient, but they did not coalesce to yield a separate phase. The liquid–condensed domains were only slightly enriched in DPPC and cholesterol, and their chemical composition remained very similar to the overall composition of the monolayer membrane. Instead, they differed from liquid-expanded regions in terms of membrane thickness (in agreement with AFM data), diffusion rates, acyl chain packing, and orientation. We hypothesize that such lateral heterogeneities are crucial for lung surfactant function, as they allow both efficient packing, to achieve low surface tension, and sufficient fluidity, critical for rapid adsorption to the air–liquid interface during the breathing cycle. url: https://doi.org/10.1101/2020.07.07.191569 doi: 10.1101/2020.07.07.191569 id: cord-264012-q2quyijg author: Lim, Su Bin title: ACE2-expressing endothelial cells in aging mouse brain date: 2020-07-11 words: 2133.0 sentences: 106.0 pages: flesch: 48.0 cache: ./cache/cord-264012-q2quyijg.txt txt: ./txt/cord-264012-q2quyijg.txt summary: Further, scRNA-seq dataset specifically derived from brain vasculature in young adult and aged mice (T3) confirms the elevated ACE2 expression in subsets of the three identified cell types, which consist of 32.8% of the cell populations ( Fig. 1 C) . While our study provides a foundation for a more refined level of analysis of EC and vascular PC, a cell type that remains poorly understood despite its key roles in immune response and microvascular stability [17] , our analyses are limited only to the normal aging mouse and human brains, lacking the context of COVID-19 neuropathology. Despite the works that failed to identify direct signs of SARS-CoV-2 infection in the brains of COVID-19 patients [12, 13] , other lines of evidence support the neurotropism of the virus, as evidenced by experimental platforms leveraging human induced pluripotent stem cell (iPSC)derived dopaminergic neurons [22] and an organotypic brain model [23] . abstract: Angiotensin-converting enzyme 2 (ACE2) is a key receptor mediating the entry of SARS-CoV-2 into the host cell. Through a systematic analysis of publicly available mouse brain sc/snRNA-seq data, we found that ACE2 is specifically expressed in small sub-populations of endothelial cells and mural cells, namely pericytes and vascular smooth muscle cells. Further, functional changes in viral mRNA transcription and replication, and impaired blood-brain barrier regulation were most prominently implicated in the aged, ACE2-expressing endothelial cells, when compared to the young adult mouse brains. Concordant EC transcriptomic changes were further found in normal aged human brains. Overall, this work reveals an outline of ACE2 distribution in the mouse brain and identify putative brain host cells that may underlie the selective susceptibility of the aging brain to viral infection. url: https://doi.org/10.1101/2020.07.11.198770 doi: 10.1101/2020.07.11.198770 id: cord-338734-laeocs3j author: Lima, Amorce title: Validation and Comparison of a Modified CDC Assay with two Commercially Available Assays for the Detection of SARS-CoV-2 in Respiratory Specimen date: 2020-06-30 words: 2533.0 sentences: 141.0 pages: flesch: 61.0 cache: ./cache/cord-338734-laeocs3j.txt txt: ./txt/cord-338734-laeocs3j.txt summary: In silico analysis and clinical sample testing showed that the primesr/probes designed by the CDC were specific to the SARS-CoV-2 as they accurately detected all reactive samples with an assay LoD of 200 copies/ml. A 149 series of two-fold dilutions of SARS-CoV-2 strain USA_WA1/2020 RNA were spiked in pooled 150 sputum at concentrations of 800 copies/ml to 0.05 copy/ml in order to determine the limit of 151 detection (LoD) of the assay. On the other hand, the average Ct values difference between 235 samples run within 2 days between DiaSorin Simplexa Covid 19 Direct assay and the modified 236 CDC SARS-CoV-2 assay was -2.42, and -6.0 between samples run within 5 days. In this study, we validated a modified CDC SARS-CoV-2 assay and compared its 263 performance to two commercial automated sample-to-answer assays for the detection of SARS-264 The difference is even greater 286 in samples that were run 5 days after the routine testing on the modified CDC SARS-CoV-2 287 assay. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has spread rapidly around the globe since it was first identified in December of 2019 in Wuhan, China. In a race to contain the infection, researchers and healthcare officials have developed several assays to help diagnose individuals with COVID-19. To help laboratories in deciding what assay to bring into testing lines, factors such as assay availability, cost, throughput, and TAT should be considered. Here we validated a modified version of the CDC assay and used it as a reference to evaluate the performance of the NeuMoDx™ SARS-CoV-2 and DiaSorin Simplexa™ Covid-19 Direct assays. In silico analysis and clinical sample testing showed that the primesr/probes designed by the CDC were specific to the SARS-CoV-2 as they accurately detected all reactive samples with an assay LoD of 200 copies/ml. The performance of the three assays were analyzed using 161 nasopharyngeal swabs specimen tested within 24 hours or 5 days from routine testing. A 100% agreement was observed between the commercial assays and the modified CDC SARS-CoV-2 assay. A deeper look at the Ct values showed no significant difference between NeuMoDx and the modified CDC SARS-CoV-2 assay, whereas DiaSorin had lower overall Ct values than the modified CDC SARS-CoV-2 assay. NeuMoDx and DiaSorin workflows were much easier to perform. NeuMoDx has the highest throughput and shortest TAT, whereas although the modified CDC SARS-CoV-2 assay has comparable throughput to DiaSorin, it has the longest hands-on time, and highest TAT. url: https://doi.org/10.1101/2020.06.29.179192 doi: 10.1101/2020.06.29.179192 id: cord-328073-bqeffvzl author: Limonta, Daniel title: Nodosome inhibition as a novel broad-spectrum antiviral strategy against arboviruses and SARS-CoV-2 date: 2020-11-06 words: 1878.0 sentences: 113.0 pages: flesch: 55.0 cache: ./cache/cord-328073-bqeffvzl.txt txt: ./txt/cord-328073-bqeffvzl.txt summary: The studies were prompted by the observation that infection of human fetal brain cells with Zika virus (ZIKV) induces expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a host factor that was found to promote ZIKV replication and spread. A drug that targets NOD2 was shown to have potent broad-spectrum antiviral activity against other flaviviruses, alphaviruses and SARS-CoV-2, the causative agent of COVID-19. Next, we demonstrated that the NOD2 inhibitor GSK717 blocks infection by and 205 spread of ZIKV in human fetal brain and cell lines. Similarly, the work here which demonstrated the antiviral activity of NOD2 and RIPK2 inhibitors using tissue explants, 216 primary cells and cell lines, support the potential clinical use of these compounds in mono or co-217 infections by arboviruses as well as coronavirus infections at early and/or advanced stages. Calu-3 and Huh7 cells infected with SARS-CoV-2 (MOI=0.1) were also treated with GSK583 for 24 hours before collecting the cell supernatants for viral titer determination. abstract: In the present report, we describe two small molecules with broad-spectrum antiviral activity. These drugs block formation of the nodosome. The studies were prompted by the observation that infection of human fetal brain cells with Zika virus (ZIKV) induces expression of nucleotide-binding oligomerization domain-containing protein 2 (NOD2), a host factor that was found to promote ZIKV replication and spread. A drug that targets NOD2 was shown to have potent broad-spectrum antiviral activity against other flaviviruses, alphaviruses and SARS-CoV-2, the causative agent of COVID-19. Another drug that inhibits the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) which functions downstream of NOD2, also decreased replication of these pathogenic RNA viruses. The broad-spectrum action of nodosome targeting drugs is mediated, at least in part, by enhancement of the interferon response. Together, these results suggest that further preclinical investigation of nodosome inhibitors as potential broad-spectrum antivirals is warranted. url: https://doi.org/10.1101/2020.11.05.370767 doi: 10.1101/2020.11.05.370767 id: cord-102608-1ilforzm author: Litviňuková, Monika title: Cells and gene expression programs in the adult human heart date: 2020-04-10 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Cardiovascular disease is the leading cause of death worldwide. Advanced insights into disease mechanisms and strategies to improve therapeutic opportunities require deeper understanding of the molecular processes of the normal heart. Knowledge of the full repertoire of cardiac cells and their gene expression profiles is a fundamental first step in this endeavor. Here, using large-scale single cell and nuclei transcriptomic profiling together with state-of-the-art analytical techniques, we characterise the adult human heart cellular landscape covering six anatomical cardiac regions (left and right atria and ventricles, apex and interventricular septum). Our results highlight the cellular heterogeneity of cardiomyocytes, pericytes and fibroblasts, revealing distinct subsets in the atria and ventricles indicative of diverse developmental origins and specialized properties. Further we define the complexity of the cardiac vascular network which includes clusters of arterial, capillary, venous, lymphatic endothelial cells and an atrial-enriched population. By comparing cardiac cells to skeletal muscle and kidney, we identify cardiac tissue resident macrophage subsets with transcriptional signatures indicative of both inflammatory and reparative phenotypes. Further, inference of cell-cell interactions highlight a macrophage-fibroblast-cardiomyocyte network that differs between atria and ventricles, and compared to skeletal muscle. We expect this reference human cardiac cell atlas to advance mechanistic studies of heart homeostasis and disease. url: https://doi.org/10.1101/2020.04.03.024075 doi: 10.1101/2020.04.03.024075 id: cord-102977-yci9kq6x author: Liu, Haiming title: GHSR-1a is not Required for Ghrelin’s Anti-inflammatory and Fat-sparing Effects in Cancer Cachexia date: 2019-12-06 words: 4891.0 sentences: 291.0 pages: flesch: 59.0 cache: ./cache/cord-102977-yci9kq6x.txt txt: ./txt/cord-102977-yci9kq6x.txt summary: This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma (LLC)-induced cachexia model and those mediating the effects of ghrelin in Ghsr+/+ and Ghsr−/− mice. GHSR-1a is not expressed in adipocytes (Sun, Garcia et 243 al., 2007) but is present in macrophages (Ma, Lin et al., 2013) and our findings are consistent with a 244 previous report showing that old, non-tumor-bearing Ghsr -/mice have reduced macrophage 245 infiltration, a shift on macrophage differentiation towards a more anti-inflammatory phenotype, and 246 decreased inflammation in adipose tissue (Lin, Lee et al., 2016) . In this study, we did 278 not see a significant effect of ghrelin on preventing LLC-induced fat browning, BAT thermogenesis, 279 increased REE or decreased physical activity in the setting of CACS despite the fact that ghrelin 280 prevented fat and weight loss and anorexia. abstract: Adipose tissue (AT) atrophy is a hallmark of cancer cachexia contributing to increased morbidity/mortality. Ghrelin has been proposed as a treatment for cancer cachexia partly by preventing AT atrophy. However, the mechanisms mediating ghrelin’s effects are incompletely understood, including the extent to which its only known receptor, GHSR-1a, is required for these effects. This study characterizes the pathways involved in AT atrophy in the Lewis Lung Carcinoma (LLC)-induced cachexia model and those mediating the effects of ghrelin in Ghsr+/+ and Ghsr−/− mice. We show that LLC causes AT atrophy by inducing anorexia, and increasing AT inflammation, thermogenesis and energy expenditure. These changes were greater in Ghsr−/−. Ghrelin administration prevented LLC-induced anorexia only in Ghsr+/+, but prevented WAT inflammation and atrophy in both genotypes, although its effects were greater in Ghsr+/+. LLC-induced increases in BAT inflammation, WAT and BAT thermogenesis, and energy expenditure were not affected by ghrelin. In conclusion, ghrelin ameliorates WAT inflammation, fat atrophy and anorexia in LLC-induced cachexia. GHSR-1a is required for ghrelin’s orexigenic effect but not for its anti-inflammatory or fat-sparing effects. url: https://doi.org/10.1101/866376 doi: 10.1101/866376 id: cord-277253-vy0mvzeb author: Liu, Hongbo title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro date: 2020-04-11 words: 2265.0 sentences: 154.0 pages: flesch: 52.0 cache: ./cache/cord-277253-vy0mvzeb.txt txt: ./txt/cord-277253-vy0mvzeb.txt summary: title: Scutellaria baicalensis extract and baicalein inhibit replication of SARS-CoV-2 and its 3C-like protease in vitro We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. Inspired by the previous studies, several covalent inhibitors were experimentally identified to inhibit the 3CL pro activity and viral replication of SARS-CoV-2, and some of the complex crystal structures were solved [14, 15] . baicalensis inhibits SARS-CoV-2 3CL pro activity and the most active ingredient baicalein exhibits an IC50 of 0.39 M. We also identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CL pro activity at microM concentration. baicalensis and tested its inhibitory activity against SARS-CoV-2 3CL pro . baicalensis extract at different concentrations on SARS-CoV-2 3CL pro activity were 6 shown in Figure 1A . abstract: COVID-19 has become a global pandemic that threatens millions of people worldwide. There is an urgent call for developing effective drugs against the virus (SARS-CoV-2) causing this disease. The main protease of SARS-CoV-2, 3C-like protease (3CLpro), is highly conserved across coronaviruses and is essential for the maturation process of viral polyprotein. Scutellariae radix (Huangqin in Chinese), the root of Scutellaria baicalensis has been widely used in traditional Chinese medicine to treat viral infection related symptoms. The extracts of S. baicalensis have exhibited broad spectrum antiviral activities. We studied the anti-SARS-CoV-2 activity of S. baicalensis and its ingredient compounds. We found that the ethanol extract of S. baicalensis inhibits SARS-CoV-2 3CLpro activity in vitro and the replication of SARS-CoV-2 in Vero cells with an EC50 of 0.74 μg/ml. Among the major components of S. baicalensis, baicalein strongly inhibits SARS-CoV-2 3CLpro activity with an IC50 of 0.39 μM. We further identified four baicalein analogue compounds from other herbs that inhibit SARS-CoV-2 3CLpro activity at microM concentration. Our study demonstrates that the extract of S. baicalensis has effective anti-SARS-CoV-2 activity and baicalein and analogue compounds are strong SARS-CoV-2 3CLpro inhibitors. url: https://doi.org/10.1101/2020.04.10.035824 doi: 10.1101/2020.04.10.035824 id: cord-258630-mvz2l3yj author: Liu, Tiantian title: A benchmarking study of SARS-CoV-2 whole-genome sequencing protocols using COVID-19 patient samples date: 2020-11-10 words: 11041.0 sentences: 596.0 pages: flesch: 57.0 cache: ./cache/cord-258630-mvz2l3yj.txt txt: ./txt/cord-258630-mvz2l3yj.txt summary: We compared seven different library construction protocols and specifically evaluated the cross-protocol performance in sequencing read mappability, viral genome coverage percentage and uniformity, effect of sequence depth, SNV calling concordance (reproducibility), precision (positive predictive value), and sensitivity (proportion of consensus variants identified at different sequencing depths and viral copy number inputs) across protocols. Here, we compared seven WGS protocols for SARS-CoV-2 using clinical samples from infected patients, benchmarking the performances of these protocols in several aspects including the sequencing read mappability, genome coverage (percentage and uniformity, minimum sequences required); sample storage condition; effects of viral input, sequencing depth, length and platform; sensitivity, reproducibility and precision of SNV calling and related assay factors (e.g., amount of viral input, sequencing depth and bioinformatics pipeline). abstract: The COVID-19 pandemic is a once-in-a-lifetime event, exceeding mortality rates of the flu pandemics from the 1950’s and 1960’s. Whole-genome sequencing (WGS) of SARS-CoV-2 plays a critical role in understanding the disease. Performance variation exists across SARS-CoV-2 viral WGS technologies, but there is currently no benchmarking study comparing different WGS sequencing protocols. We compared seven different SARS-CoV-2 WGS library protocols using RNA from patient nasopharyngeal swab samples under two storage conditions. We constructed multiple WGS libraries encompassing three different viral inputs: 1,000,000, 250,000 and 1,000 copies. Libraries were sequenced using two distinct platforms with varying sequencing depths and read lengths. We found large differences in mappability and genome coverage, and variations in sensitivity, reproducibility and precision of single-nucleotide variant calling across different protocols. We ranked the performance of protocols based on six different metrics. Our results indicated that the most appropriate protocol depended on viral input amount and sequencing depth. Our findings offer guidance in choosing appropriate WGS protocols to characterize SARS-CoV-2 and its evolution. url: https://doi.org/10.1101/2020.11.10.375022 doi: 10.1101/2020.11.10.375022 id: cord-273416-332stbjl author: Liu, Tianyuan title: Transcriptional differences for COVID-19 Disease Map genes between males and females indicate a different basal immunophenotype relevant to the disease date: 2020-10-01 words: 2739.0 sentences: 124.0 pages: flesch: 46.0 cache: ./cache/cord-273416-332stbjl.txt txt: ./txt/cord-273416-332stbjl.txt summary: We created DeCovid, an R shiny app that combines gene expression data of different human tissue from the Genotype-Tissue Expression (GTEx) project and the COVID-19 Disease Map gene collection to explore basal gene expression differences across healthy demographic groups. In this paper, we present the DeCovid app, a Shiny app, to explore basal expression level differences in COVID-19 disease map genes between men and women and different age groups. The DeCovid shiny app combines a selection of human tissue specific GTEx data with the COVID-19 Disease Map database to allow quick exploration of basal gene expression values and differences in the healthy human population for genes described to be important for COVID-19. Here we present the DeCovid app as a resource to explore sex and age differential expression patterns in the healthy population for genes described to be involved in COVID-19 disease pathways. abstract: Worldwide COVID-19 epidemiology data indicate clear differences in disease incidence among sex and age groups. Specifically, male patients are at a higher death risk than females. However, whether this difference is the consequence of a pre-existing sex-bias in immune genes or a differential response to the virus has not been studied yet. We created DeCovid, an R shiny app that combines gene expression data of different human tissue from the Genotype-Tissue Expression (GTEx) project and the COVID-19 Disease Map gene collection to explore basal gene expression differences across healthy demographic groups. We used this app to study differential gene expression between men and women for COVID-19 associated genes. We identified that healthy women present higher levels in the expression of interferon genes and the JAK-STAT pathway leading to cell survival. url: https://doi.org/10.1101/2020.09.30.321059 doi: 10.1101/2020.09.30.321059 id: cord-348729-kejlm425 author: Liu, Xiaoyu title: Neutralizing Antibodies Isolated by a site-directed Screening have Potent Protection on SARS-CoV-2 Infection date: 2020-05-04 words: 3457.0 sentences: 178.0 pages: flesch: 50.0 cache: ./cache/cord-348729-kejlm425.txt txt: ./txt/cord-348729-kejlm425.txt summary: SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. These determined infection mechanisms indicated that blocking the interaction of SARS-CoV-2-RBD and ACE2 would cause a direct neutralizing effect against virus. This information suggests that the ACE2 interface of SARS-CoV-2-RBD might have high immunogenicity, which would be a suitable targeting epitope to develop SARS-CoV-2-specific antibodies with potent neutralizing function by in vitro screening. We performed site-directed antibody screening by phage display and finally obtained one IgG antibody and three single domain antibodies with potent neutralizing activities for SARS-CoV-2. Notably, the eluted phage exhibited a stronger binding signal on SARS-CoV-2-RBD compared to that on SARS-CoV-2-RBD mut, especially those from the domain antibody library ( Figure 2C ), indicating an expected precleaning effect during selection. abstract: Neutralizing antibody is one of the most effective interventions for acute pathogenic infection. Currently, over three million people have been identified for SARS-CoV-2 infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are still lacking. SARS-CoV-2 infects host cells by interacting with angiotensin converting enzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spike glycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 by antibody would cause a directly neutralizing effect against virus. In the current study, we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope for neutralizing antibody screening. We performed site-directed screening by phage display and finally obtained one IgG antibody (4A3) and several domain antibodies. Among them, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to act as neutralizing antibodies due to their capabilities to block the interaction between SARS-CoV-2-RBD and ACE2-positive cells. The domain antibody 4A12 was predicted to have the best accessibility to all three ACE2-interfaces on the spike homotrimer. Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all four antibodies could potently protect host cells from virus infection. Overall, we isolated multiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibody screening, which could be promising candidate drugs for the prevention and treatment of COVID-19. url: https://doi.org/10.1101/2020.05.03.074914 doi: 10.1101/2020.05.03.074914 id: cord-305054-4d84b2g6 author: Liu, Yuan title: The selection of reference genome and the search for the origin of SARS-CoV-2 date: 2020-08-11 words: 2166.0 sentences: 140.0 pages: flesch: 60.0 cache: ./cache/cord-305054-4d84b2g6.txt txt: ./txt/cord-305054-4d84b2g6.txt summary: The assembly obtained using RaTG13 as reference showed better statistics in total length and N50 than the assembly guided by SARS-CoV-2, indicating that RaTG13 maybe a better reference for assembling CoV in pangolin or other potential intermediate hosts. Zhang, Wu, and Zhang [13] re-analyzed the RNA-Seq reads from two pangolins carrying coronavirus using reference-guided de novo assembly method, with Wuhan-Hu-1 as the reference genome. They also performed RNA sequencing in five archived pangolins samples from Guangdong, and assembled the genomes using WIV04, another SARS-CoV-2 genome from human, as reference genome. Using de novo assembly method, they obtained viral genome that showed 90.32% and 90.24% of whole genome identify to Wuhan-Hu-1and Bat-CoV RaTG13, respectively. RaTG13, which is a bat CoV, had 1,287 reads mapped to it, and the resulting assembly has total length of 21,925 and N50 of 1,428. abstract: The pandemic caused by SARS-CoV-2 has a great impact on the whole world. In a theory of the origin of SARS-CoV-2, pangolins were considered a potential intermediate host. To assemble the coronavirus found in pangolins, SARS-CoV-2 were used a reference genome in most of studies, assuming that pangolins CoV and SARS-CoV-2 are the closest neighbors in the evolution. However, this assumption may not be true. We investigated how the selection of reference genome affect the resulting CoV genome assembly. We explored various representative CoV as reference genome, and found significant differences in the resulting assemblies. The assembly obtained using RaTG13 as reference showed better statistics in total length and N50 than the assembly guided by SARS-CoV-2, indicating that RaTG13 maybe a better reference for assembling CoV in pangolin or other potential intermediate hosts. url: https://doi.org/10.1101/2020.08.10.245290 doi: 10.1101/2020.08.10.245290 id: cord-349015-5oisrm5s author: Liu, Zhe title: Identification of a common deletion in the spike protein of SARS-CoV-2 date: 2020-04-02 words: 1182.0 sentences: 63.0 pages: flesch: 57.0 cache: ./cache/cord-349015-5oisrm5s.txt txt: ./txt/cord-349015-5oisrm5s.txt summary: In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. By sequencing the whole genome of SARS-CoV-2, we identified two variants having deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. To investigate whether these deletions described above are random mutations occasionally identified in a strain or would commonly occur after cell passages, we performed whole genome sequencing on the other 21 SARS-CoV-2 viral strains collected after 2 rounds of cell passage in Vero-E6 or Vero cells (Supplemental Table) . abstract: Two notable features have been identified in the SARS-CoV-2 genome: (1) the receptor binding domain of SARS-CoV-2; (2) a unique insertion of twelve nucleotide or four amino acids (PRRA) at the S1 and S2 boundary. For the first feature, the similar RBD identified in SARs-like virus from pangolin suggests the RBD in SARS-CoV-2 may already exist in animal host(s) before it transmitted into human. The left puzzle is the history and function of the insertion at S1/S2 boundary, which is uniquely identified in SARS-CoV-2. In this study, we identified two variants from the first Guangdong SARS-CoV-2 cell strain, with deletion mutations on polybasic cleavage site (PRRAR) and its flank sites. More extensive screening indicates the deletion at the flank sites of PRRAR could be detected in 3 of 68 clinical samples and half of 22 in vitro isolated viral strains. These data indicate (1) the deletion of QTQTN, at the flank of polybasic cleavage site, is likely benefit the SARS-CoV-2 replication or infection in vitro but under strong purification selection in vivo since it is rarely identified in clinical samples; (2) there could be a very efficient mechanism for deleting this region from viral genome as the variants losing 23585-23599 is commonly detected after two rounds of cell passage. The mechanistic explanation for this in vitro adaptation and in vivo purification processes (or reverse) that led to such genomic changes in SARS-CoV-2 requires further work. Nonetheless, this study has provided valuable clues to aid further investigation of spike protein function and virus evolution. The deletion mutation identified in vitro isolation should be also noted for current vaccine development. url: https://doi.org/10.1101/2020.03.31.015941 doi: 10.1101/2020.03.31.015941 id: cord-103872-yzqic5vt author: Liu, Zhijin title: Global view on virus infection in non-human primates and implication for public health and wildlife conservation date: 2020-05-13 words: 1310.0 sentences: 81.0 pages: flesch: 51.0 cache: ./cache/cord-103872-yzqic5vt.txt txt: ./txt/cord-103872-yzqic5vt.txt summary: Research has revealed that SARS-CoV-2 and other coronaviruses have been transmitted from animals to humans and vice versa, and across animal species, and hence, attracted public attention concerning host-virus interactions and transmission ways. We suggest epidemiological investigations in NHPs, specifically in Old World monkeys with close contact to humans, and other effective measures to prevent this potential circular transmission. First, we generated a summary statistics of worldwide reported VI-NHPs. We then 61 identified and predicted NHP species with a high risk of virus transmission from humans and 62 predicted geographic locations where disease outbreaks are likely to occur. Since centrality in primate-virus networks could assess the potential for the 72 circulation of viruses among NHPs and humans, we estimated the centrality using four metrics: 73 strength degree centrality, eigenvector centrality, betweenness centrality, and closeness centrality 74 implemented in the R package "igraph" and UCINET 6. Centrality in primate-parasite networks 225 reveals the potential for the transmission of emerging infectious diseases to humans abstract: The pandemic outbreak and rapid worldwide spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is not only a threat for humans, but potentially also for many animals. Research has revealed that SARS-CoV-2 and other coronaviruses have been transmitted from animals to humans and vice versa, and across animal species, and hence, attracted public attention concerning host-virus interactions and transmission ways. Non-human primates (NHPs), as our evolutionary closest relatives, are susceptible to human viruses, and a number of pathogens are known to circulate between humans and NHPs. Here we generated global statistics of virus infection in NHPs (VI-NHPs). In total, 121 NHP species from 14 families have been reported to be infected by 139 DNA and RNA viruses from 23 virus families; 74.8 percent of viruses in NHPs have also been found in humans, indicative of the high potential for cross species transmission of these viruses. The top ten NHP species with high centrality in the NHP-virus network are two apes (Pan troglodytes, Pongo pygmaeus), seven Old World monkeys (Macaca mulatta, M. fascicularis, Papio cynocephalus, Lophocebus albigena, Chlorocebus aethiops, Cercopithecus ascanius, C. nictitans) and a lemur (Propithecus diadema). Besides apes, there is a high risk of virus circulation between humans and Old World monkeys, given the wide distribution of many Old World monkey species and their frequent contact with humans. We suggest epidemiological investigations in NHPs, specifically in Old World monkeys with close contact to humans, and other effective measures to prevent this potential circular transmission. url: https://doi.org/10.1101/2020.05.12.089961 doi: 10.1101/2020.05.12.089961 id: cord-314072-av3r7it7 author: Liu, Zhuoming title: Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization date: 2020-11-08 words: 1105.0 sentences: 74.0 pages: flesch: 54.0 cache: ./cache/cord-314072-av3r7it7.txt txt: ./txt/cord-314072-av3r7it7.txt summary: title: Landscape analysis of escape variants identifies SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization To define the immune-mediated mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor binding domain (RBD) to generate 48 escape mutants. Although each mAb had unique resistance profiles, many shared residues within an epitope, as several variants were resistant to multiple mAbs. Remarkably, we identified mutants that escaped neutralization by convalescent human sera, suggesting that some humans induce a narrow repertoire of neutralizing antibodies. By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, we identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans. To select for SARS-CoV-2 S variants that escape neutralization, we used VSV-SARSas we isolated this mutation alone, and acquisition of the L517R substitution appeared to 141 increase viral fitness as judged by plaque morphology (Fig S2) . abstract: Although neutralizing antibodies against the SARS-CoV-2 spike (S) protein are a goal of most COVID-19 vaccines and being developed as therapeutics, escape mutations could compromise such countermeasures. To define the immune-mediated mutational landscape in S protein, we used a VSV-eGFP-SARS-CoV-2-S chimeric virus and 19 neutralizing monoclonal antibodies (mAbs) against the receptor binding domain (RBD) to generate 48 escape mutants. These variants were mapped onto the RBD structure and evaluated for cross-resistance by convalescent human plasma. Although each mAb had unique resistance profiles, many shared residues within an epitope, as several variants were resistant to multiple mAbs. Remarkably, we identified mutants that escaped neutralization by convalescent human sera, suggesting that some humans induce a narrow repertoire of neutralizing antibodies. By comparing the antibody-mediated mutational landscape in S protein with sequence variation in circulating SARS-CoV-2 strains, we identified single amino acid substitutions that could attenuate neutralizing immune responses in some humans. url: https://doi.org/10.1101/2020.11.06.372037 doi: 10.1101/2020.11.06.372037 id: cord-102632-yazl9usb author: Lobet, Guillaume title: QuoVidi: a open-source web application for the organisation of large scale biological treasure hunts date: 2020-07-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Learning biology, and in particular systematics, requires learning a substantial amount of specific vocabulary, both for botanical and zoological studies. While crucial, the precise identification of structures serving as evolutionary traits and systematic criteria is not per se a highly motivating task for students. Teaching this in a traditional teaching setting is quite challenging especially with a large crowd of students to be kept engaged. This is even more difficult if, as during the COVID-19 crisis, students are not allowed to access laboratories for hands-on observation on fresh specimens and sometimes restricted to short-range movements outside their home. Here we present QuoVidi, a new open-source web platform for the organisation of large scale treasure hunts. The platform works as follows: students, organised in teams, receive a list of quests that contain morphologic, ecologic or systematic terms. They have to first understand the meaning of the quests, then go and find them in the environment. Once they find the organism corresponding to a quest, they upload a geotagged picture of their finding and submit this on the platform. The correctness of each submission is evaluated by the staff. During the COVID-19 lockdown, previously validated pictures were also submitted for evaluation to students that were locked in low-biodiversity areas. From a research perspective, the system enables the creation of large image databases by the students, similar to citizen-science projects. Beside the enhanced motivation of students to learn the vocabulary and perform observations on self-found specimens, this system allows faculties to remotely follow and assess the work performed by large numbers of students. The interface is freely available, open-source and customizable. It can be used in other disciplines with adapted quests and we expect it to be of interest in many classroom settings. url: https://doi.org/10.1101/2020.06.30.177006 doi: 10.1101/2020.06.30.177006 id: cord-343517-vf32wxkx author: Lokman, Syed Mohammad title: Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach date: 2020-04-11 words: 2745.0 sentences: 163.0 pages: flesch: 53.0 cache: ./cache/cord-343517-vf32wxkx.txt txt: ./txt/cord-343517-vf32wxkx.txt summary: However, SARS-CoV-2 has emerged with remarkable properties like glutamine-rich 42 aa long exclusive molecular signature (DSQQTVGQQDGSEDNQTTTIQTIVEVQPQLEMELTPVVQTIE) in position 983-1024 of polyprotein 1ab (pp1ab) [16] , diversified receptor-binding domain (RBD), unique furin cleavage site (PRRAR↓SV) at S1/S2 boundary in S glycoprotein which could play roles in viral pathogenesis, diagnosis and treatment [17] . There is growing evidence that spike protein, a 1273 amino acid long glycoprotein having multiple domains, possibly plays a major role in SARS-CoV-2 pathogenesis. In this study, we have analyzed 320 genomic sequences of SARS-CoV-2 to identify mutations between the available genomes followed by the amino acid variations in the glycoprotein S to foresee their impact on the viral entry to host cell from structural biology viewpoint. The evolutionary distances showed that all the SARS-CoV-2 spike proteins cluster in the same node of the phylogenetic tree confirming the sequences are similar to Refseq YP_009724390 (Fig. 2) . abstract: The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation. url: https://doi.org/10.1101/2020.04.07.030924 doi: 10.1101/2020.04.07.030924 id: cord-102279-ena1usqv author: Long, Rory K. M. title: Super Resolution Microscopy and Deep Learning Identify Zika Virus Reorganization of the Endoplasmic Reticulum date: 2020-06-23 words: 3681.0 sentences: 275.0 pages: flesch: 55.0 cache: ./cache/cord-102279-ena1usqv.txt txt: ./txt/cord-102279-ena1usqv.txt summary: projections of 3D STED image stacks show high intensity ERmoxGFP and Sec61β-GFP labeling in a 89 CER region and low intensity labeling in PER tubules in mock-infected cells ( Figure 1A ), as reported 90 previously by diffraction limited confocal microscopy (3). Density-based segmentation of the ERmoxGFP-96 and Sec61β-GFP-labelled ER of ZIKV-infected cells showed that the higher density crescent-shaped 97 CER region exhibited significant overlap with dsRNA-positive ER structures relative to the rest of 98 the ER ( Figure 1B ). Morphological comparison of the dsRNA-positive and -negative CER of 133 ZIKV-infected cells with the CER of mock-infected cells showed that the CER was composed of a 134 convoluted network of tubules for both the ERmoxGFP-and Sec61β-labeled ER ( Figure 3B ). 3D STED analysis showed a predominant distribution of both NS2B and 149 NS4B to the CER and more particularly to the dense ZIKV-induced crescent-shaped tubular matrix 150 in ERmoxGFP transfected U87 cells ( Figure 5A ). abstract: The endoplasmic reticulum (ER) is a complex subcellular organelle composed of diverse structures such as tubules, sheets and tubular matrices. Flaviviruses such as Zika virus (ZIKV) induce reorganization of endoplasmic reticulum (ER) membranes to facilitate viral replication. Here, using 3D super resolution microscopy, ZIKV infection is shown to induce the formation of dense tubular matrices associated with viral replication in the central ER. Viral non-structural proteins NS4B and NS2B associate with replication complexes within the ZIKV-induced tubular matrix and exhibit distinct ER distributions outside this central ER region. Deep neural networks trained to identify ZIKV-infected versus mock-infected cells successfully identified ZIKV-induced central ER tubular matrices as a determinant of viral infection. Super resolution microscopy and deep learning are therefore able to identify and localize morphological features of the ER and may be of use to screen for inhibitors of infection by ER-reorganizing viruses. url: https://doi.org/10.1101/2020.05.12.091611 doi: 10.1101/2020.05.12.091611 id: cord-334313-v2syspu6 author: Long, S. Wesley title: Molecular Architecture of Early Dissemination and Evolution of the SARS-CoV-2 Virus in Metropolitan Houston, Texas date: 2020-05-03 words: 4525.0 sentences: 251.0 pages: flesch: 48.0 cache: ./cache/cord-334313-v2syspu6.txt txt: ./txt/cord-334313-v2syspu6.txt summary: We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. Because in vitro resistance of SARS-CoV to remdesivir has been reported to be caused by either of two amino acid replacements in RdRp (Phe476Leu and Val553Leu), we interrogated our data for polymorphisms in the nsp12 gene. abstract: We sequenced the genomes of 320 SARS-CoV-2 strains from COVID-19 patients in metropolitan Houston, Texas, an ethnically diverse region with seven million residents. These genomes were from the viruses causing infections in the earliest recognized phase of the pandemic affecting Houston. Substantial viral genomic diversity was identified, which we interpret to mean that the virus was introduced into Houston many times independently by individuals who had traveled from different parts of the country and the world. The majority of viruses are apparent progeny of strains derived from Europe and Asia. We found no significant evidence of more virulent viral types, stressing the linkage between severe disease, underlying medical conditions, and perhaps host genetics. We discovered a signal of selection acting on the spike protein, the primary target of massive vaccine efforts worldwide. The data provide a critical resource for assessing virus evolution, the origin of new outbreaks, and the effect of host immune response. Significance COVID-19, the disease caused by the SARS-CoV-2 virus, is a global pandemic. To better understand the first phase of virus spread in metropolitan Houston, Texas, we sequenced the genomes of 320 SARS-CoV-2 strains recovered from COVID-19 patients early in the Houston viral arc. We identified no evidence that a particular strain or its progeny causes more severe disease, underscoring the connection between severe disease, underlying health conditions, and host genetics. Some amino acid replacements in the spike protein suggest positive immune selection is at work in shaping variation in this protein. Our analysis traces the early molecular architecture of SARS-CoV-2 in Houston, and will help us to understand the origin and trajectory of future infection spikes. url: https://doi.org/10.1101/2020.05.01.072652 doi: 10.1101/2020.05.01.072652 id: cord-287658-c2lljdi7 author: Lopez-Rincon, Alejandro title: Classification and Specific Primer Design for Accurate Detection of SARS-CoV-2 Using Deep Learning date: 2020-09-10 words: 4766.0 sentences: 253.0 pages: flesch: 55.0 cache: ./cache/cord-287658-c2lljdi7.txt txt: ./txt/cord-287658-c2lljdi7.txt summary: The discovered sequences are first validated on samples from other repositories, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. The discovered sequences are validated on samples from NCBI and GISAID, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. For example, we can use this sequencing data with cDNA, resulting from the PCR of the original viral RNA; e,g, Real-Time PCR amplicons to identify the SARS-CoV-2 16 . The global impact of SARS-CoV-2 prompted researchers to apply effective alignment-free methods to the classification of the virus: For example, in 26 the authors propose the use of Machine Learning Digital Signal Processing for separating the virus from similar strains, with remarkable accuracy. We calculated the frequency of appearance of different primer sets'' sequences used in SARS-CoV-2 RT-PCR tests developed by WHO referral laboratories and compared it to our primer design in the dataset from the GISAID ( Table 2) repository. abstract: In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from available repositories, separating the genome of different virus strains from the Coronavirus family with considerable accuracy. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are first validated on samples from other repositories, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets on existing datasets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. In this paper, deep learning is coupled with explainable artificial intelligence techniques for the discovery of representative genomic sequences in SARS-CoV-2. A convolutional neural network classifier is first trained on 553 sequences from NGDC, separating the genome of different virus strains from the Coronavirus family with accuracy 98.73%. The network’s behavior is then analyzed, to discover sequences used by the model to identify SARS-CoV-2, ultimately uncovering sequences exclusive to it. The discovered sequences are validated on samples from NCBI and GISAID, and proven able to separate SARS-CoV-2 from different virus strains with near-perfect accuracy. Next, one of the sequences is selected to generate a primer set, and tested against other state-of-the-art primer sets, obtaining competitive results. Finally, the primer is synthesized and tested on patient samples (n=6 previously tested positive), delivering a sensibility similar to routine diagnostic methods, and 100% specificity. The proposed methodology has a substantial added value over existing methods, as it is able to both identify promising primer sets for a virus from a limited amount of data, and deliver effective results in a minimal amount of time. Considering the possibility of future pandemics, these characteristics are invaluable to promptly create specific detection methods for diagnostics. url: https://doi.org/10.1101/2020.03.13.990242 doi: 10.1101/2020.03.13.990242 id: cord-102868-wnsgjdcp author: Love, R. Rebecca title: Inversion Genotyping in the Anopheles gambiae Complex Using High-Throughput Array and Sequencing Platforms date: 2020-05-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Chromosomal inversion polymorphisms have special importance in the Anopheles gambiae complex of malaria vector mosquitoes, due to their role in local adaptation and range expansion. The study of inversions in natural populations is reliant on polytene chromosome analysis by expert cytogeneticists, a process that is limited by the rarity of trained specialists, low throughput, and restrictive sampling requirements. To overcome this barrier, we ascertained tag single nucleotide polymorphisms (SNPs) that are highly correlated with inversion status (inverted or standard orientation). We compared the performance of the tag SNPs using two alternative high throughput molecular genotyping approaches versus traditional cytogenetic karyotyping of the same 960 individual An. gambiae and An. coluzzii mosquitoes sampled from Burkina Faso, West Africa. We show that both molecular approaches yield comparable results, and that either one performs as well or better than cytogenetics in terms of genotyping accuracy. Given the ability of molecular genotyping approaches to be conducted at scale and at relatively low cost without restriction on mosquito sex or developmental stage, molecular genotyping via tag SNPs has the potential to revitalize research into the role of chromosomal inversions in the behavior and ongoing adaptation of An. gambiae and An. coluzzii to environmental heterogeneities. url: https://doi.org/10.1101/2020.05.25.114793 doi: 10.1101/2020.05.25.114793 id: cord-326282-uxn64olw author: Lu, Maolin title: Real-time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles date: 2020-09-13 words: 3264.0 sentences: 207.0 pages: flesch: 55.0 cache: ./cache/cord-326282-uxn64olw.txt txt: ./txt/cord-326282-uxn64olw.txt summary: To measure conformational dynamics of the SARS-CoV-2 S trimer on the surface of virus particles, we established two types of particles, lentiviral pseudoparticles carrying S, as well as coronaviruslike particles generated by expression of S, membrane (M), envelope (E) and nucleocapsid (N) 15 protein (S-MEN)(24, 25) (Fig. 1, A and B ). Analyses of smFRET data from ligand-free S protein on lentiviral particles revealed that the SARS-CoV-2 S protein is dynamic, sampling at least four distinct conformational states To identify the receptor-bound conformation of the SARS-CoV-2 S protein by smFRET, we measured the conformational consequences of soluble, monomeric hACE2 binding. Addition of 5 the monomeric hACE2 receptor to surface-immobilized virus particles lead to increased occupancy of the low-(~0.1) FRET S protein conformation (Fig. 2E) , which was observed at both the single-molecule and population level (Fig. 2F ). Relative state-occupancy and fitting parameters in each of four FRET-defined conformational states of SARS-CoV-2 spike protein on the surface of virus particles. abstract: SARS-CoV-2 spike (S) mediates entry into cells and is critical for vaccine development against COVID-19. Structural studies have revealed distinct conformations of S, but real-time information that connects these structures, is lacking. Here we apply single-molecule Förster Resonance Energy Transfer (smFRET) imaging to observe conformational dynamics of S on virus particles. Virus-associated S dynamically samples at least four distinct conformational states. In response to hACE2, S opens sequentially into the hACE2-bound S conformation through at least one on-path intermediate. Conformational preferences of convalescent plasma and antibodies suggest mechanisms of neutralization involving either competition with hACE2 for binding to RBD or allosteric interference with conformational changes required for entry. Our findings inform on mechanisms of S recognition and conformations for immunogen design. url: https://doi.org/10.1101/2020.09.10.286948 doi: 10.1101/2020.09.10.286948 id: cord-103077-sh4w2mye author: Lu, Shuai title: Leveraging Sequential and Spatial Neighbors Information by Using CNNs Linked With GCNs for Paratope Prediction date: 2020-10-16 words: 3140.0 sentences: 194.0 pages: flesch: 55.0 cache: ./cache/cord-103077-sh4w2mye.txt txt: ./txt/cord-103077-sh4w2mye.txt summary: In this article, we propose a method to identify which amino acid residues of an antibody directly interact with its associated antigen based on the features from sequence and structure. Our algorithm uses convolution neural networks (CNNs) linked with graph convolution networks (GCNs) to make use of information from both sequential and spatial neighbors to understand more about the local environment of the target amino acid residue. According to the type of selecting neighbors of target residue for representing and predicting, the machine learning-based methods can be divided into two categories, leveraging sequential neighbors or spatial neighbors. And the stateof-art method [19] represented an antibody as a graph where each amino acid residue was a node and K nearest spatial neighbors were used in the convolution operator. In this work, we utilize the sequential and spatial neighbors of the target antibody residue by using Convolutional Neural Networks (CNNs) linked with Graph Neural Networks (GCNs) for paratope prediction. abstract: Antibodies consisting of variable and constant regions, are a special type of proteins playing a vital role in immune system of the vertebrate. They have the remarkable ability to bind a large range of diverse antigens with extraordinary affinity and specificity. This malleability of binding makes antibodies an important class of biological drugs and biomarkers. In this article, we propose a method to identify which amino acid residues of an antibody directly interact with its associated antigen based on the features from sequence and structure. Our algorithm uses convolution neural networks (CNNs) linked with graph convolution networks (GCNs) to make use of information from both sequential and spatial neighbors to understand more about the local environment of the target amino acid residue. Furthermore, we process the antigen partner of an antibody by employing an attention layer. Our method improves on the state-of-the-art methodology. url: https://doi.org/10.1101/2020.10.15.339168 doi: 10.1101/2020.10.15.339168 id: cord-328585-1rkrrx8a author: Lu, Shuai title: The immunodominant and neutralization linear epitopes for SARS-CoV-2 date: 2020-08-27 words: 2954.0 sentences: 254.0 pages: flesch: 69.0 cache: ./cache/cord-328585-1rkrrx8a.txt txt: ./txt/cord-328585-1rkrrx8a.txt summary: To investigate the spectrum of antibodies in COVID-19 patients, we detected the binding of the 155 early convalescent sera of 8 imported (Europe) cases which infected SARS-CoV-2 in early April, 156 2020 and 12 domestic (China) cases in early February, 2020 to various epitopes ( Table 1) K203R204/G189R203G204/R203G204/R203G204S344 in N protein, respectively (Table 1) , 172 resulting in different immunodominant epitopes of different virus sub-strains which provide the 173 bases for the differential diagnosis. The predicted epitopes induce neutralization antibody production 175 SARS-CoV-2 pseudo-virus neutralization assay is a well-accepted method to detect the ability of 176 vaccine to inhibit SARS-CoV-2 infection . To assess 8 neutralization antibodies induced by S protein epitopes, we incubated the immunization sera with 178 D614 or G614 SARS-CoV-2 pseudo-viruses and then the mixture was added to ACE2-293FT 179 cells which stably expressed ACE2. abstract: The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) becomes a tremendous threat to global health. Although vaccines against the virus are under development, the antigen epitopes on the virus and their immunogenicity are poorly understood. Here, we simulated the three-dimensional structures of SARS-CoV-2 proteins with high performance computer, predicted the B cell epitopes on spike (S), envelope (E), membrane (M), and nucleocapsid (N) proteins of SARS-CoV-2 using structure-based approaches, and then validated the epitope immunogenicity by immunizing mice. Almost all 33 predicted epitopes effectively induced antibody production, six of which were immunodominant epitopes in patients identified via the binding of epitopes with the sera from domestic and imported COVID-19 patients, and 23 were conserved within SARS-CoV-2, SARS-CoV and bat coronavirus RaTG13. We also found that the immunodominant epitopes of domestic SARS-CoV-2 were different from that of the imported, which may be caused by the mutations on S (G614D) and N proteins. Importantly, we validated that eight epitopes on S protein elicited neutralizing antibodies that blocked the cell entry of both D614 and G614 pseudo-virus of SARS-CoV-2, three and nine epitopes induced D614 or G614 neutralizing antibodies, respectively. Our present study shed light on the immunodominance, neutralization, and conserved epitopes on SARS-CoV-2 which are potently used for the diagnosis, virus classification and the vaccine design tackling inefficiency, virus mutation and different species of coronaviruses. url: https://doi.org/10.1101/2020.08.27.267716 doi: 10.1101/2020.08.27.267716 id: cord-273645-czh3zfb3 author: Lu, Shuaiyao title: Comparison of SARS-CoV-2 infections among 3 species of non-human primates date: 2020-07-17 words: 2197.0 sentences: 171.0 pages: flesch: 65.0 cache: ./cache/cord-273645-czh3zfb3.txt txt: ./txt/cord-273645-czh3zfb3.txt summary: In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Here, to establish the COVID-19 model, two families including 3 species of non-human primates, which are widely used for animal models with their own advantages and disadvantages, were experimentally infected with SARS-CoV-2, followed by comparisons of clinical symptoms, hematology, biochemical indexes, immunology and histopathology among 3 species. Given that host factors may be involved in viral pathogenesis, we designed an experiment in the present study to investigate whether host genetics, age and gender affect SARS-CoV-2 infection in non-human primates ( Figure 1 ). To know dynamics of viral replication and virus shedding, samples of nasal swabs, throat swabs, anal swabs, feces, blood and tissues were collected at the indicated time points, and SARS-CoV-2 genomes were quantitated by RT-qPCR. abstract: COVID-19, caused by SARS-CoV-2 infection, has recently been announced as a pandemic all over the world. Plenty of diagnostic, preventive and therapeutic knowledges have been enriched from clinical studies since December 2019. However, animal models, particularly non-human primate models, are urgently needed for critical questions that could not be answered in clinical patients, evaluations of anti-viral drugs and vaccines. In this study, two families of non-human primates, Old world monkeys (12 Macaca mulatta, 6 Macaca fascicularis) and New world monkeys (6 Callithrix jacchus), were experimentally inoculated with SARS-CoV-2. Clinical signs were recorded. Samples were collected for analysis of viral shedding, viremia and histopathological examination. Increased body temperature was observed in 100% (12/12) M. mulatta, 33.3% (2/6) M. fascicularis and none (0/6) of C. jacchus post inoculation of SARS-CoV-2. All of M. mulatta and M. fascicularis showed chest radiographic abnormality. Viral genomes were detected in nasal swabs, throat swabs, anal swabs and blood from all 3 species of monkeys. Viral shedding from upper respiratory samples reached the peak between day 6 and day 8 post inoculation. From necropsied M. mulatta and M. fascicularis, the tissues showing virus positive were mainly lung, weasand, bronchus and spleen. No viral genome was seen in any of tissues from 2 necropsied C. jacchus. Severe gross lesions and histopathological changes were observed in lung, heart and stomach of SARS-CoV-2 infected animals. In summary, we have established a NHP model for COVID-19, which could be used to evaluate drugs and vaccines, and investigate viral pathogenesis. M. mulatta is the most susceptible to SARS-CoV-2 infection, followed by M. fascicularis and C. jacchus. One Sentence Summary M. mulatta is the most susceptible to SARS-CoV-2 infection as compared to M. fascicularis and C. jacchus. url: https://doi.org/10.1101/2020.04.08.031807 doi: 10.1101/2020.04.08.031807 id: cord-344949-9zyz4hll author: Luban, Jeremy title: The DHODH Inhibitor PTC299 Arrests SARS-CoV-2 Replication and Suppresses Induction of Inflammatory Cytokines date: 2020-08-05 words: 5552.0 sentences: 277.0 pages: flesch: 47.0 cache: ./cache/cord-344949-9zyz4hll.txt txt: ./txt/cord-344949-9zyz4hll.txt summary: a Selectivity index is the ratio of CC50 to EC50 b values are mean ± standard deviation (SD) Abbreviations: CC50, compound concentration at which cell number is reduced by 50%; EC50, compound concentration at which viral replication on a linear scale is inhibited by 50%; GFP, green fluorescent protein; HCV, hepatitis C virus replicon genotype 1b; PIV-3, Parainfluenza type 3; RSV, respiratory syncytial virus; RT-qPCR, quantitative reverse transcription PCR; SARS-CoV-2, Severe acute respiratory syndrome coronavirus 2; TCID50, tissue culture infectious dose 50%. In the BT co-cell culture system, which models chronic inflammatory conditions driven by B cell activation and antibody production, incubation of cells with 10 nM PTC299 resulted in a significant reduction in the levels of soluble (s)IgG, sIL-17A, sIL-17F, sIL-6, and sTNFα released from the cells after 72 hours of stimulation (range, 49% to 68%) (all p values <0.01) ( Figure 4 and Table 2 ). abstract: The coronavirus disease 2019 (COVID-19) pandemic has created an urgent need for therapeutics that inhibit the SARS-CoV-2 virus and suppress the fulminant inflammation characteristic of advanced illness. Here, we describe the anti-COVID-19 potential of PTC299, an orally available compound that is a potent inhibitor of dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme of the de novo pyrimidine biosynthesis pathway. In tissue culture, PTC299 manifests robust, dose-dependent, and DHODH-dependent inhibition of SARS CoV-2 replication (EC50 range, 2.0 to 31.6 nM) with a selectivity index >3,800. PTC299 also blocked replication of other RNA viruses, including Ebola virus. Consistent with known DHODH requirements for immunomodulatory cytokine production, PTC299 inhibited the production of interleukin (IL)-6, IL-17A (also called IL-17), IL-17F, and vascular endothelial growth factor (VEGF) in tissue culture models. The combination of anti-SARS-CoV-2 activity, cytokine inhibitory activity, and previously established favorable pharmacokinetic and human safety profiles render PTC299 a promising therapeutic for COVID-19. url: https://doi.org/10.1101/2020.08.05.238394 doi: 10.1101/2020.08.05.238394 id: cord-313215-diqfmitr author: Luo, Lei title: Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases date: 2020-07-09 words: 1593.0 sentences: 90.0 pages: flesch: 52.0 cache: ./cache/cord-313215-diqfmitr.txt txt: ./txt/cord-313215-diqfmitr.txt summary: title: Air and surface contamination in non-health care settings among 641 environmental specimens of 39 COVID-19 cases Background Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. To address this question, in this study, we sampled total of 641 surfaces 63 environmental and air specimens among 39 cases in Guangzhou, China, to explore the 64 surrounding environmental surfaces and air contamination by SARS-CoV-2 in non-65 health care settings. A total of 641 157 environmental surfaces and air specimens were collected among 39 COVID-19 cases, 158 and 20 specimens (20/641, 3.1%) were positive by RT-PCR testing from 9 COVID-19 159 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic 160 cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases 161 ( of SARS-CoV-2 (Table 2) . abstract: Background Little is known about the SARS-CoV-2 contamination of environmental surfaces and air in non-health care settings among COVID-19 cases. Methods and findings We explored the SARS-CoV-2 contamination of environmental surfaces and air by collecting air and swabbing environmental surfaces among 39 COVID-19 cases in Guangzhou, China. The specimens were tested by RT-PCR testing. The information collected for COVID-19 cases included basic demographic, clinical severity, onset of symptoms, radiological testing, laboratory testing and hospital admission. A total of 641 environmental surfaces and air specimens were collected among 39 COVID-19 cases before disinfection. Among them, 20 specimens (20/641, 3.1%) were tested positive from 9 COVID-19 cases (9/39, 23.1%), with 5 (5/101, 5.0%) positive specimens from 3 asymptomatic cases, 5 (5/220, 2.3%) from 3 mild cases, and 10 (10/374, 2.7%) from 3 moderate cases. All positive specimens were collected within 3 days after diagnosis, and 10 (10/42, 23.8%) were found in toilet (5 on toilet bowl, 4 on sink/faucet/shower, 1 on floor drain), 4 (4/21, 19.0%) in anteroom (2 on water dispenser/cup/bottle, 1 on chair/table, 1 on TV remote), 1 (1/8, 12.5%) in kitchen (1 on dining-table), 1 (1/18, 5.6%) in bedroom (1 on bed/sheet pillow/bedside table), 1 (1/5, 20.0%) in car (1 on steering wheel/seat/handlebar) and 3 (3/20, 21.4%) on door knobs. Air specimens in room (0/10, 0.0%) and car (0/1, 0.0%) were all negative. Conclusions SARS-CoV-2 was found on environmental surfaces especially in toilet, and could survive for several days. We provided evidence of potential for SARS-CoV-2 transmission through contamination of environmental surfaces. url: https://doi.org/10.1101/2020.07.09.195008 doi: 10.1101/2020.07.09.195008 id: cord-347804-kxhasabe author: Luo, Ruibang title: Tracking cytosine depletion in SARS-CoV-2 date: 2020-10-26 words: 1084.0 sentences: 69.0 pages: flesch: 63.0 cache: ./cache/cord-347804-kxhasabe.txt txt: ./txt/cord-347804-kxhasabe.txt summary: Results We built a website to track the composition change of mono-, di-, and tri-nucleotide of SARS-CoV-2 over time. Using 137,315 SARS-CoV-2 strains collected in ten months, we observed cytosine depletion at a rate of about one cytosine loss per month from the whole genome. We built an interactive website at http://www.bio8.cs.hku.hk/sarscov2 to show the mono-, di-, and tri-nucleotide composition trends of the whole genome and single genes. In Table 1 , we first compared the composition of nucleotides in multiple coronaviruses, including SARS-CoV-2 (an average of 76 strands collected from Dec 20, 2019 to Feb 15, 2020), SARS, MERS, and four that causes a common cold. Compared to SARS-CoV-2, which we assumed a relative mortality level of 3, the percentage of cytosine is lower in almost all of the eleven genes in the four common cold coronaviruses with a lower mortality level 1. The results are available on an interactive website at http://www.bio8.cs.hku.hk/sarscov2. abstract: Motivation Danchin et al. have pointed out that cytosine drives the evolution of SARS-CoV-2. A depletion of cytosine might lead to the attenuation of SARS-CoV-2. Results We built a website to track the composition change of mono-, di-, and tri-nucleotide of SARS-CoV-2 over time. The website downloads new strains available from GISAID and updates its results daily. Our analysis suggests that the composition of cytosine in coronaviruses is related to their reported mortality. Using 137,315 SARS-CoV-2 strains collected in ten months, we observed cytosine depletion at a rate of about one cytosine loss per month from the whole genome. Availability The website is available at http://www.bio8.cs.hku.hk/sarscov2/. Contact rbluo@cs.hku.hk Supplementary information Supplementary data are available at Bioinformatics online. url: https://doi.org/10.1101/2020.10.26.354787 doi: 10.1101/2020.10.26.354787 id: cord-284354-aoti88v7 author: Lupala, Cecylia S. title: Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 date: 2020-05-04 words: 968.0 sentences: 63.0 pages: flesch: 59.0 cache: ./cache/cord-284354-aoti88v7.txt txt: ./txt/cord-284354-aoti88v7.txt summary: title: Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2 It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. Angiotensin-converting 302 enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential 303 therapeutic target Computational simulations reveal the binding dynamics between human 318 ACE2 and the receptor binding domain of SARS-CoV-2 spike protein Computational Design of Peptides to Block Binding of 327 the SARS-CoV-2 Spike Protein to Human ACE2 abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2. url: https://doi.org/10.1101/2020.05.03.075473 doi: 10.1101/2020.05.03.075473 id: cord-297747-kifqgskc author: Lupala, Cecylia S. title: Computational simulations reveal the binding dynamics between human ACE2 and the receptor binding domain of SARS-CoV-2 spike protein date: 2020-03-27 words: 4522.0 sentences: 231.0 pages: flesch: 57.0 cache: ./cache/cord-297747-kifqgskc.txt txt: ./txt/cord-297747-kifqgskc.txt summary: Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. When this study was started, neither the crystal structure of the SARS-CoV-2 spike protein nor the RBD segment were determined, so the homology modeling approach was applied to construct the model of the SARS-CoV-2 spike RBD in complex with the human ACE2 binding domain (denoted as CoV2-RBD/ACE2 in the following). Although the crystal structure and the predicted model of the CoV2-RBD/ACE2 complex provide important information about the binding interactions at the molecular interfaces, MD simulations can extend the knowledge to a dynamics regime in a fully solvated environment. abstract: A novel coronavirus (the SARS-CoV-2) has been identified in January 2020 as the causal pathogen for COVID-19 pneumonia, an outbreak started near the end of 2019 in Wuhan, China. The SARS-CoV-2 was found to be closely related to the SARS-CoV, based on the genomic analysis. The Angiotensin converting enzyme 2 protein (ACE2) utilized by the SARS-CoV as a receptor was found to facilitate the infection of SARS-CoV-2 as well, initiated by the binding of the spike protein to the human ACE2. Using homology modeling and molecular dynamics (MD) simulation methods, we report here the detailed structure of the ACE2 in complex with the receptor binding domain (RBD) of the SARS-CoV-2 spike protein. The predicted model is highly consistent with the experimentally determined complex structures. Plausible binding modes between human ACE2 and the RBD were revealed from all-atom MD simulations. The simulation data further revealed critical residues at the complex interface and provided more details about the interactions between the SARS-CoV-2 RBD and human ACE2. Two mutants mimicking rat ACE2 were modeled to study the mutation effects on RBD binding to ACE2. The simulations showed that the N-terminal helix and the K353 of the human ACE2 alter the binding modes of the CoV2-RBD to the ACE2. url: https://doi.org/10.1101/2020.03.24.005561 doi: 10.1101/2020.03.24.005561 id: cord-104055-47ren7ie author: Lutkenhoff, Evan S. title: EEG power spectra and subcortical pathology in chronic disorders of consciousness date: 2020-09-01 words: 2479.0 sentences: 127.0 pages: flesch: 49.0 cache: ./cache/cord-104055-47ren7ie.txt txt: ./txt/cord-104055-47ren7ie.txt summary: Objective To determine (i) the association between long-term impairment of consciousness after severe brain injury, spontaneous brain oscillations, and underlying subcortical damage, and (ii) whether such data can be used to aid patient diagnosis, a process known to be susceptible to high error rates. Conclusions These results ground, for the first time, electroencephalographic presentation detected with routine clinical techniques in the underlying brain pathology of disorders of consciousness and demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of this patient cohort. Sex, 19 age, time-post-injury, etiology (i.e., TBI vs non-TBI), were included as covariates, 20 along with NBV (to ensure that observed tissue displacement reflect local subcortical 21 shape changes independent of overall brain atrophy ( In this analysis, we related the patients'' behavioral presentation, as captured by the 7 CRS-R subscales, with subcortical atrophy. abstract: Objective To determine (i) the association between long-term impairment of consciousness after severe brain injury, spontaneous brain oscillations, and underlying subcortical damage, and (ii) whether such data can be used to aid patient diagnosis, a process known to be susceptible to high error rates. Methods Cross-sectional observational sample of 116 patients with a disorder of consciousness secondary to brain injury, collected prospectively at a tertiary center between 2011 and 2013. Multimodal analyses relating clinical measures of impairment, electroencephalographic measures of spontaneous brain activity, and magnetic resonance imaging data of subcortical atrophy were conducted in 2018. Results In the final analyzed sample of 61 patients, systematic associations were found between electroencephalographic power spectra and subcortical damage. Specifically, the ratio of beta-to-delta relative power was negatively associated with greater atrophy in regions of the bilateral thalamus and globus pallidus (both left > right) previously shown to be preferentially atrophied in chronic disorders of consciousness. Power spectrum total density was also negatively associated with widespread atrophy in regions of the left globus pallidus, right caudate, and in brainstem. Furthermore, we showed that the combination of demographics, encephalographic, and imaging data in an analytic framework can be employed to aid behavioral diagnosis. Conclusions These results ground, for the first time, electroencephalographic presentation detected with routine clinical techniques in the underlying brain pathology of disorders of consciousness and demonstrate how multimodal combination of clinical, electroencephalographic, and imaging data can be employed in potentially mitigating the high rates of misdiagnosis typical of this patient cohort. Search terms disorders of consciousness, subcortical pathology, EEG, MRI. url: https://doi.org/10.1101/695288 doi: 10.1101/695288 id: cord-322654-6nccarjn author: Luzes, Rafael title: Angiotensin-(3–4) modulates angiotensin converting enzyme 2 (ACE2) downregulation in proximal tubule cells due to overweight and undernutrition: implications regarding the severity of renal lesions in Covid-19 infection date: 2020-06-29 words: 1447.0 sentences: 89.0 pages: flesch: 52.0 cache: ./cache/cord-322654-6nccarjn.txt txt: ./txt/cord-322654-6nccarjn.txt summary: title: Angiotensin-(3–4) modulates angiotensin converting enzyme 2 (ACE2) downregulation in proximal tubule cells due to overweight and undernutrition: implications regarding the severity of renal lesions in Covid-19 infection Since the renin-angiotensin-aldosterone system (RAAS) has been implicated in the progress of kidney failure during Covid-19, we also investigated the influence of Angiotensin-(3–4) (Ang-(3–4)) the shortest angiotensin-derived peptide, which is considered the physiological antagonist of several angiotensin II effects. That Ang-(3-4)-mediated upregulation of renal ACE2 126 occurred in overweight rats, but not in the CTR group, is indicative that a "pro-127 hypertensive tissular microenvironment" (high Ang II) develops in animals fed with a 128 diet rich in lipids, causing downregulation of ACE2 (Figure 2A The influence of chronic undernutrition on renal ACE2 levels present some 132 similarity, but also a huge difference, compared with overweight rats (Figure 3) . abstract: The renal lesions – including severe acute kidney injury – are severe outcomes in SARS-CoV-2 infections. There are no reports regarding the influence of the nutritional status on the severity and progress of these lesions. Ageing is also an important risk factor. In the present communication we compare the influence of overweight and undernutrition in the levels of renal angiotensin converting enzymes 1 and 2. Since the renin-angiotensin-aldosterone system (RAAS) has been implicated in the progress of kidney failure during Covid-19, we also investigated the influence of Angiotensin-(3–4) (Ang-(3–4)) the shortest angiotensin-derived peptide, which is considered the physiological antagonist of several angiotensin II effects. We found that both overweight and undernutrition downregulate the levels of angiotensin converting enzyme 2 (ACE2) without influence on the levels of ACE1 in kidney rats. Administration of Ang-(3–4) recovers the control levels of ACE2 in overweight but not in undernourished rats. We conclude that chronic and opposite nutritional conditions play a central role in the pathophysiology of renal Covid-19 lesions, and that the role of RAAS is also different in overweight and undernutrition. url: https://doi.org/10.1101/2020.06.29.178293 doi: 10.1101/2020.06.29.178293 id: cord-102367-l1u094bp author: López, María S. title: Dengue arbovirus affecting temperate Argentina province for more than a decade 2009-2020 date: 2020-08-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dengue disease is found in tropical and subtropical climates and within the last decade it has extended to temperate regions. Santa Fe, a temperate province in Argentina, has experienced an increase in dengue cases and virus circulation in the last decade, with the recent 2020 outbreak being the largest since dengue transmission was first reported in the province in 2009. The aim of this work is to perform a description of spatio-temporal fluctuations of dengue (DENV) cases from 2009 to the present in Santa Fe province. The data presented in this work provide a detailed description of dengue virus transmission for Santa Fe province by department. This information is useful to assist in better understanding the impact of ongoing dengue emergence in temperate regions across the world. Indeed, this work provides data useful for future studies including those investigating socio-ecological, climate, and environmental factors associated with dengue transmission, as well as those investigating other variables related to the biology and the ecology of vector-borne diseases. url: https://doi.org/10.1101/2020.08.11.246272 doi: 10.1101/2020.08.11.246272 id: cord-104037-39kk37fb author: Ma, Jiahao title: Cryo-EM structure of S-Trimer, a subunit vaccine candidate for COVID-19 date: 2020-09-21 words: 2720.0 sentences: 153.0 pages: flesch: 62.0 cache: ./cache/cord-104037-39kk37fb.txt txt: ./txt/cord-104037-39kk37fb.txt summary: Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. The newly-formed structural motif makes 152 direct contact with the previously identified pH switch 1 of the adjacent protomer, 153 accounting for the enhanced stability of the WT S-Trimer at lower pH (Fig. 3A) . When revisiting the electron density map for full-163 length wild-type S protein (EMDB: 22292), we spotted unassigned density at the become predominant over the ancestral form worldwide and has been shown to interaction with K854 at the conformational switch region (Fig. 4C ). Purified MT S-trimer protein diluted to 0.2 and 0.5 mg/ml in PBS buffer were applied to glow-discharged gold holey carbon 1.2/1.3 300-mesh grids with and without graphene oxide, respectively. abstract: Less than a year after its emergence, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 22 million people worldwide with a death toll approaching 1 million. Vaccination remains the best hope to ultimately put this pandemic to an end. Here, using Trimer-Tag technology, we produced both wild-type (WT) and furin site mutant (MT) S-Trimers for COVID-19 vaccine studies. Cryo-EM structures of the WT and MT S-Trimers, determined at 3.2 Å and 2.6 Å respectively, revealed that both antigens adopt a tightly closed conformation and their structures are essentially identical to that of the previously solved full-length WT S protein in detergent. These results validate Trimer-Tag as a platform technology in production of metastable WT S-Trimer as a candidate for COVID-19 subunit vaccine. url: https://doi.org/10.1101/2020.09.21.306357 doi: 10.1101/2020.09.21.306357 id: cord-343476-0chuwvg6 author: MacLean, Oscar A. title: Evidence of significant natural selection in the evolution of SARS-CoV-2 in bats, not humans date: 2020-05-29 words: 1386.0 sentences: 73.0 pages: flesch: 51.0 cache: ./cache/cord-343476-0chuwvg6.txt txt: ./txt/cord-343476-0chuwvg6.txt summary: Here we contrast the role of positive selection and recombination in the Sarbecoviruses in horseshoe bats to SARS-CoV-2 evolution in humans. While methods can detect some evidence for positive selection in SARS-CoV-2, we demonstrate these are mostly due to recombination and sequencing artefacts. For all but two of the ten positive selected codons, this signal was being driven by apparent convergent evolution (or homoplasy) in the tree, with the same mutation occurring in parallel across the phylogeny. To investigate whether this observation was truly due to independent events or because of recombination signatures in the SARS-CoV-2 outbreak tree, we firstly determined if the samples with these convergent mutations were geographically correlated. The Spike V367F signal was driven by apparent convergent evolution between four french samples sequenced in January and a Hong Kong sample 412028, which shows shared variation either side of the homoplasy suggesting it is not a recombinant (Supplementary figure 3C) . abstract: RNA viruses are proficient at switching to novel host species due to their fast mutation rates. Implicit in this assumption is the need to evolve adaptations in the new host species to exploit their cells efficiently. However, SARS-CoV-2 has required no significant adaptation to humans since the pandemic began, with no observed selective sweeps to date. Here we contrast the role of positive selection and recombination in the Sarbecoviruses in horseshoe bats to SARS-CoV-2 evolution in humans. While methods can detect some evidence for positive selection in SARS-CoV-2, we demonstrate these are mostly due to recombination and sequencing artefacts. Purifying selection is also substantially weaker in SARS-CoV-2 than in the related bat Sarbecoviruses. In comparison, our results show evidence for positive, specifically episodic selection, acting on the bat virus lineage SARS-CoV-2 emerged from. This signature of selection can also be observed among synonymous substitutions, for example, linked to ancestral CpG depletion on this bat lineage. We show the bat virus RmYN02 has recombinant CpG content in Spike pointing to coinfection and evolution in bats without involvement of other species. Our results suggest the non-human progenitor of SARS-CoV-2 was capable of human-human transmission as a consequence of its natural evolution in bats. url: https://www.ncbi.nlm.nih.gov/pubmed/32577659/ doi: 10.1101/2020.05.28.122366 id: cord-103341-q7yqnvm2 author: MacPherson, Ailene title: A General Birth-Death-Sampling Model for Epidemiology and Macroevolution date: 2020-10-11 words: 2672.0 sentences: 167.0 pages: flesch: 55.0 cache: ./cache/cord-103341-q7yqnvm2.txt txt: ./txt/cord-103341-q7yqnvm2.txt summary: As an illustration of the utility of our mathematical approach, we use our approach to derive a yet unstudied variant of the birth-death process in which the key rates emerge deterministically from a classic susceptible infected recovered (SIR) epidemiological model. Similarly, in the case of past CSAs we must 99 include the probability, r l , that sampled hosts are removed from the infectious pool during the CSA at time 100 ary case to explicitly model the collection of samples from the fossil record (e.g., the fossilized birth-death 102 process [19]). Step 6: Conditioning the likelihood -Finally, we condition the likelihood on observing at least one lineage 285 given the TMRCA, Here we derive a phylogenetic birth-death-sampling model in a more general form than previously attempted, 294 making as few assumptions about the processes that generated the data as possible. abstract: Birth-death stochastic processes are the foundation of many phylogenetic models and are widely used to make inferences about epidemiological and macroevolutionary dynamics. There are a large number of birth-death model variants that have been developed; these impose different assumptions about the temporal dynamics of the parameters and about the sampling process. As each of these variants was individually derived, it has been difficult to understand the relationships between them as well as their precise biological and mathematical assumptions. And without a common mathematical foundation, deriving new models is non-trivial. Here we unify these models into a single framework, prove that many previously developed epidemiological and macroevolutionary models are all special cases of a more general model, and illustrate the connections between these variants. To do so, we develop a novel technique for deriving likelihood functions for arbitrarily complex birth-death(-sampling) models that will allow researchers to explore a wider array of scenarios than was previously possible. As an illustration of the utility of our mathematical approach, we use our approach to derive a yet unstudied variant of the birth-death process in which the key rates emerge deterministically from a classic susceptible infected recovered (SIR) epidemiological model. url: https://doi.org/10.1101/2020.10.10.334383 doi: 10.1101/2020.10.10.334383 id: cord-104138-qagyaegp author: Magee, Michelle title: Effects of face masks on acoustic analysis and speech perception: Implications for peri-pandemic protocols date: 2020-10-08 words: 2183.0 sentences: 138.0 pages: flesch: 52.0 cache: ./cache/cord-104138-qagyaegp.txt txt: ./txt/cord-104138-qagyaegp.txt summary: Here we investigated how three face mask types (N95, surgical and cloth) affect acoustic analysis of speech and perceived intelligibility in healthy subjects. We compared speech produced with and without the different masks on acoustic measures of timing, frequency, perturbation and power spectral density. Our data show that face masks change the speech signal, but some specific acoustic features remain largely unaffected (e.g., measures of voice quality) irrespective of mask type. Where the interaction was significant, planned comparisons were made for each 1Khz frequency band to determine differences between masks types compared to no mask. For recordings produced with the tabletop microphone, there was a significant effect of mask type for percentage of pauses (F3,7.87=8.17, p=0.008), and spectral tilt (F3,8.39=15.43, p=0.001) ( Table 1) . We observed significant differences in acoustic power distribution across relevant frequency bands for speech in all three mask conditions compared to no mask. abstract: Wearing face masks (alongside physical distancing) provides some protection against infection from COVID-19. Face masks can also change how we communicate and subsequently affect speech signal quality. Here we investigated how three face mask types (N95, surgical and cloth) affect acoustic analysis of speech and perceived intelligibility in healthy subjects. We compared speech produced with and without the different masks on acoustic measures of timing, frequency, perturbation and power spectral density. Speech clarity was also examined using a standardized intelligibility tool by blinded raters. Mask type impacted the power distribution in frequencies above 3kHz for both the N95 and surgical masks. Measures of timing and spectral tilt also differed across mask conditions. Cepstral and harmonics to noise ratios remained flat across mask type. No differences were observed across conditions for word or sentence intelligibility measures. Our data show that face masks change the speech signal, but some specific acoustic features remain largely unaffected (e.g., measures of voice quality) irrespective of mask type. Outcomes have bearing on how future speech studies are run when personal protective equipment is worn. url: https://doi.org/10.1101/2020.10.06.327452 doi: 10.1101/2020.10.06.327452 id: cord-102967-dx0tg077 author: Mahajan, Lakshmi S. title: Mapping RNA dependent RNA polymerase activity and immune gene expression using PRO-seq date: 2020-06-16 words: 2853.0 sentences: 163.0 pages: flesch: 57.0 cache: ./cache/cord-102967-dx0tg077.txt txt: ./txt/cord-102967-dx0tg077.txt summary: Coupled to PRO-seq in human blood samples, we propose to use PRO-seq as a single package method to detect (+)ssRNA virus RdRp activity and its interaction with host immune response through transcriptome-wide profiling of leukocyte gene expressions at once. This is different from Drosophila RNA Polymerase II, which appears to have comparable substrate specificity for all 4 biotin-NTPs. The ORF-proximal accumulation coincides with quadruplet rich regions of the template-strand of the DAV genome ( Figure 1D ). From this data, we did not detect significant PRO-seq sequences from (+)ssRNA viral genomes, indicating that none of the individuals had direct viral infections in the blood immune cells. Our PRO-seq data show expression levels of immune-response related genes from human peripheral blood leukocytes. PRO-seq density on DAV genome and base-quadruplet counts.The read count is indicated along the left side of each graph. Base-pair-resolution genome-wide mapping of active RNA polymerases using precision nuclear run-on (PRO-seq) abstract: Positive strand, single strand RNA viruses ((+)ssRNA viruses) are viruses with an RNA genome that have broad impacts on a wide range of hosts, including SARS-CoV-2 human respiratory infections. Their replication and gene expression are driven by RNA dependent RNA polymerases (RdRp). Detecting active RNA synthesis by RdRp is critical for assessing the infectivity and pathogenicity of (+)ssRNA viruses. Current approaches rely on viral RNA detection, which cannot distinguish viral titer from RdRp activity. Precision Run-On sequencing (PRO-seq) is a nuclear run-on based nascent RNA sequencing method, widely used to map eukaryotic RNA polymerases by using labeled nucleotide analogues. Here we provide evidence that PRO-seq also detects RdRp activity and can serve as a highly sensitive RdRp mapping method. Coupled to PRO-seq in human blood samples, we propose to use PRO-seq as a single package method to detect (+)ssRNA virus RdRp activity and its interaction with host immune response through transcriptome-wide profiling of leukocyte gene expressions at once. url: https://doi.org/10.1101/2020.06.15.151738 doi: 10.1101/2020.06.15.151738 id: cord-281141-ouno4jpl author: Mahajan, Swapnil title: Immunodominant T-cell epitopes from the SARS-CoV-2 spike antigen reveal robust pre-existing T-cell immunity in unexposed individuals date: 2020-11-05 words: 6208.0 sentences: 307.0 pages: flesch: 52.0 cache: ./cache/cord-281141-ouno4jpl.txt txt: ./txt/cord-281141-ouno4jpl.txt summary: A selected pool of 11 predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. We performed T-cell activation assay using the selected 11 epitopes from the SARS-CoV-2 spike antigen in unexposed donors. As shown in Figure Multiple studies have reported pre-existing T-cell immunity in unexposed donors using spike peptide pools and attributed the response to T-cells recognizing epitopes from common coldcausing coronaviruses to which a large section of the global population is exposed (7, 8, 10) . A recent large-scale study mapped a few immunogenic regions in the SARS-CoV-2 proteome responsible for expanding many unique TCRs in a large number of convalescent COVID-19 patients and unexposed healthy donors (21) . abstract: The COVID-19 pandemic has revealed a range of disease phenotypes in infected patients with asymptomatic, mild or severe clinical outcomes, but the mechanisms that determine such variable outcomes remain unresolved. In this study, we identified immunodominant CD8 T-cell epitopes in the RBD and the non-RBD domain of the spike antigen using a novel TCR-binding algorithm. A selected pool of 11 predicted epitopes induced robust T-cell activation in unexposed donors demonstrating pre-existing CD4 and CD8 T-cell immunity to SARS-CoV-2 antigen. The T-cell reactivity to the predicted epitopes was higher than the Spike-S1 and S2 peptide pools containing 157 and 158 peptides both in unexposed donors and in convalescent patients suggesting that strong T-cell epitopes are likely to be missed when larger peptide pools are used in assays. A key finding of our study is that pre-existing T-cell immunity to SARS-CoV-2 is contributed by TCRs that recognize common viral antigens such as Influenza and CMV, even though the viral epitopes lack sequence identity to the SARS-CoV-2 epitopes. This finding is in contrast to multiple published studies in which pre-existing T-cell immunity is suggested to arise from shared epitopes between SARS-CoV-2 and other common cold-causing coronaviruses. Whether the presence of pre-existing T-cell immunity provides protection against COVID-19 or contributes to severe disease phenotype remains to be determined in a larger cohort. However, our findings raise the expectation that a significant majority of the global population is likely to have SARS-CoV-2 reactive T-cells because of prior exposure to flu and CMV viruses, in addition to common cold-causing coronaviruses. url: https://doi.org/10.1101/2020.11.03.367375 doi: 10.1101/2020.11.03.367375 id: cord-103363-efd80dgn author: Mahan, Margaret title: tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports date: 2019-03-21 words: 2392.0 sentences: 159.0 pages: flesch: 44.0 cache: ./cache/cord-103363-efd80dgn.txt txt: ./txt/cord-103363-efd80dgn.txt summary: title: tbiExtractor: A framework for extracting traumatic brain injury common data elements from radiology reports Here, we set out to develop and validate a framework to extract pertinent clinical conditions for traumatic brain injury (TBI) from computed tomography (CT) reports. Materials and Methods We developed tbiExtractor, which extends pyConTextNLP, a regular expression algorithm using negation detection and contextual features, to create a framework for extracting TBI common data elements from radiology reports. The algorithm inputs radiology reports and outputs a structured summary containing 27 clinical findings with their respective annotations. Discussion and Conclusion tbiExtractor is a validated algorithm for extraction of TBI common data elements from radiology reports. At this stage of processing, each sentence in the radiology report will be marked with lexical 245 targets and linked lexical modifiers. With the nature of TBIs, some visible pathologies are only seen on follow-up CTs developed to automate the extraction of TBI common data elements from 438 radiology reports abstract: Objective The manual extraction of valuable data from electronic medical records is cumbersome, error-prone, and inconsistent. By automating extraction in conjunction with standardized terminology, the quality and consistency of data utilized for research and clinical purposes would be substantially improved. Here, we set out to develop and validate a framework to extract pertinent clinical conditions for traumatic brain injury (TBI) from computed tomography (CT) reports. Materials and Methods We developed tbiExtractor, which extends pyConTextNLP, a regular expression algorithm using negation detection and contextual features, to create a framework for extracting TBI common data elements from radiology reports. The algorithm inputs radiology reports and outputs a structured summary containing 27 clinical findings with their respective annotations. Development and validation of the algorithm was completed using two physician annotators as the gold standard. Results tbiExtractor displayed high sensitivity (0.92-0.94) and specificity (0.99) when compared to the gold standard. The algorithm also demonstrated a high equivalence (94.6%) with the annotators. A majority of clinical findings (85%) had minimal errors (F1 Score ≥ 0.80). When compared to annotators, tbiExtractor extracted information in significantly less time (0.3 sec vs 1.7 min per report). Discussion and Conclusion tbiExtractor is a validated algorithm for extraction of TBI common data elements from radiology reports. This automation reduces the time spent to extract structured data and improves the consistency of data extracted. Lastly, tbiExtractor can be used to stratify subjects into groups based on visible damage by partitioning the annotations of the pertinent clinical conditions on a radiology report. url: https://doi.org/10.1101/585331 doi: 10.1101/585331 id: cord-263825-g8p2lsr0 author: Maldonado, Lucas L. title: Molecular features similarities between SARS-CoV-2, SARS, MERS and key human genes could favour the viral infections and trigger collateral effects date: 2020-06-25 words: 3430.0 sentences: 228.0 pages: flesch: 61.0 cache: ./cache/cord-263825-g8p2lsr0.txt txt: ./txt/cord-263825-g8p2lsr0.txt summary: Since human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on host cell machinery for replication and co-evolution, we selected the genes that are highly expressed in the tissue of human lungs to perform computational studies that permit to compare their molecular features with SARS, SARS-CoV-2 and MERS genes. Furthermore, we provided a list of candidate human genes whose molecular features match those of SARS-CoV-2, SARSand MERS genes, which should be considered to be incorporated into genetic population studies to evaluate thesusceptibility to respiratory viral infections caused by these viruses. SARSand MERS genes, which should be considered to be incorporated into genetic 28 population studies to evaluate thesusceptibility to respiratory viral infections caused by 29 these viruses.The results presented here, settle the basis for further research in the field 30 of human genetics associated with the new viral infection, COVID-19, caused by 31 SARS-CoV-2 and for the development of antiviral preventive methods. abstract: In December 2019 rising pneumonia cases caused by a novel β-coronavirus (SARS-CoV-2) occurred in Wuhan, China, which has rapidly spread worldwide causing thousands of deaths. The WHO declared the SARS-CoV-2 outbreak as a public health emergency of international concern therefore several scientists are dedicated to the study of the new virus. Since human viruses have codon usage biases that match highly expressed proteins in the tissues they infect and depend on host cell machinery for replication and co-evolution, we selected the genes that are highly expressed in the tissue of human lungs to perform computational studies that permit to compare their molecular features with SARS, SARS-CoV-2 and MERS genes. In our studies, we analysed 91 molecular features for 339 viral genes and 463 human genes that consisted of 677873 codon positions. Hereby, we found that A/T bias in viral genes could propitiate the viral infection favoured by a host dependant specialization using the host cell machinery of only some genes. The envelope protein E, the membrane glycoprotein M and ORF7 could have been further benefited by a high rate of A/T in the third codon position. Thereby, the mistranslation or de-regulation of protein synthesis could produce collateral effects, as a consequence of viral occupancy of the host translation machinery due tomolecular similarities with viral genes. Furthermore, we provided a list of candidate human genes whose molecular features match those of SARS-CoV-2, SARSand MERS genes, which should be considered to be incorporated into genetic population studies to evaluate thesusceptibility to respiratory viral infections caused by these viruses. The results presented here, settle the basis for further research in the field of human genetics associated with the new viral infection, COVID-19, caused by SARS-CoV-2 and for the development of antiviral preventive methods. url: https://doi.org/10.1101/2020.06.23.167072 doi: 10.1101/2020.06.23.167072 id: cord-338296-2hk7h132 author: Malla, Tek Narsingh title: Ebselen Reacts with SARS Coronavirus-2 Main Protease Crystals date: 2020-08-23 words: 490.0 sentences: 47.0 pages: flesch: 71.0 cache: ./cache/cord-338296-2hk7h132.txt txt: ./txt/cord-338296-2hk7h132.txt summary: title: Ebselen Reacts with SARS Coronavirus-2 Main Protease Crystals The SARS coronavirus 2 main protease 3CLpro tailor cuts various essential virus proteins out of long poly-protein translated from the virus RNA. Any compound that inhibits the 3CLpro is therefore a potential drug to end the pandemic. Here we show that the diffraction power of 3CLpro crystals is effectively destroyed by Ebselen. Apart from the fragments, the most promising compounds are the α-ketoamides (Fig. 1) 24 which bind tightly to the 3CLpro 1-3 . SARS CoV-2 3CLpro in its functional, dimeric form 1 . expensive, but also less known compound that binds to the 3CLpro is Ebselen 4 . Ebselen has been shown 29 to bind strongly to the CoV-2 3CLpro 4 , but the structure of the complex is unknown. show what happens when Ebselen is added to 3CLpro crystals. Accordingly, the structure of only the untreated 3CLpro can be solved. abstract: The SARS coronavirus 2 main protease 3CLpro tailor cuts various essential virus proteins out of long poly-protein translated from the virus RNA. If the 3CLpro is inhibited, the functional virus proteins cannot form and the virus cannot replicate and assemble. Any compound that inhibits the 3CLpro is therefore a potential drug to end the pandemic. Here we show that the diffraction power of 3CLpro crystals is effectively destroyed by Ebselen. It appears that Ebselen may be a widely available, relatively cost effective way to eliminate the SARS coronavirus 2. url: https://doi.org/10.1101/2020.08.10.244525 doi: 10.1101/2020.08.10.244525 id: cord-297021-fzfl08qa author: Manomaipiboon, Anan title: The new silicone N99 half-piece respirator, VJR-NMU N99: A novel and effective tool to prevent COVID-19 date: 2020-07-23 words: 3108.0 sentences: 181.0 pages: flesch: 57.0 cache: ./cache/cord-297021-fzfl08qa.txt txt: ./txt/cord-297021-fzfl08qa.txt summary: To meet the need for FFRs during a pandemic, Navamindradhiraj University has invented a new model of silicone N99 facepiece respirator by using the silicone mask and the HEPA filter normally used in the operating room (CareStar or SafeStar, Draeger, Germany) (Fig 1) . As required by Occupational Safety and Health Administration OSHA) [7] , the half piece respirators need to pass the fit test to identify those individuals who do not achieve a sufficiently good fit necessary for adequate protection. The study was conducted to achieve two specific research objectives: (1) to investigate the fit characteristics of the novel silicone mask and whether the strap adjustment can help reduce the face-seal leakage; and (2) to determine the level of performance by measuring the inward leakage of the generated aerosols with a new filter and a used filter (for up to 24 h). abstract: Filter facepiece respirators (FFRs) are critical for preventing the transmission of respiratory tract infection disease, especially the dreadful coronavirus 2 (SARs-CoV-2). The N95 mask is a prototype, high-efficiency protective device that can effectively protect against airborne pathogens of less than 0.3 μm. The N95 mask is tightly fitting and has high filtration capacity. The ongoing COVID-19 pandemic has led to a greater requirement for FFR. This rising demand greatly exceeds current production capabilities and stockpiles, resulting in shortages. To address this, our team has invented a new type of half-piece respirator made from silicone and assembled with HEPA or elastostatic filter. A variety of methods have been used to evaluate this new device, including a qualitative fit test with the Bitrex® test kit and filtration test. The preliminary results showed that the new N99 respirators pass the fit test. The filtration tests also confirmed the superiority of N99 over traditional N95 masks, with a mean performance of protection greater than 95%. For the filters, we used two types: SafeStar, which is a kind of HEPA filter; and CareStar, which is considered an elastostatic filler. CareStar was developed to filter virus and bacteria in the operating room, with a limit duration of use up to 24 h, while the safe star was designed for 72 h use and has the quality equivalent to a HEPA filter. Our study demonstrated superior filtration efficacy of both filters, more than 98% even after 24 h of use. CareStar has significantly more filtration efficacy than a safe star (p < 0.001). In conclusion, the development of our new N99 half-piece respirator should ultimately be applicable to healthcare workers with at least non-inferiority to the previously used N 95 respirators.. Currently, the adequate supply of such equipment is not feasible. The advent of the new protective device will help protect healthcare workers and replenish the shortage of N95 respirators during the COVID-19 pandemic. url: https://doi.org/10.1101/2020.07.23.217372 doi: 10.1101/2020.07.23.217372 id: cord-102931-vxkbctiz author: Mao, Kai title: Induction of RNA interference by C. elegans mitochondrial dysfunction via the DRH-1/RIG-I homologue RNA helicase and the EOL-1/RNA decapping enzyme date: 2020-06-06 words: 8680.0 sentences: 503.0 pages: flesch: 49.0 cache: ./cache/cord-102931-vxkbctiz.txt txt: ./txt/cord-102931-vxkbctiz.txt summary: Here, we report that mitochondrial dysfunction in Caenorhabditis elegans activates RNAi-directed silencing via induction of a pathway homologous to the mammalian RIG-I helicase viral response pathway. elegans compared to most animals, and surprisingly, loss of function mutations in some of those genes cause an increase in the response to siRNAs: mutations in the RdRp RRF-3, the specialized Argonaute ERGO-1, the RNA helicase ERI-6/7, or the exoribonuclease ERI-1 enhance silencing by siRNAs (Fischer et al., 2008; Kennedy et al., 2004) . We find that reduction of function mutations in a wide range of mitochondrial components robustly enhanced RNA interference-mediated silencing of endogenous genes as well as a variety of reporters of RNAi. These antiviral responses to mitochondrial dysfunction are homologous to the RIG-I-based mitochondrial response in mammals because they depend on the RIG-I homologue, the DRH-1 RNA helicase. Our analysis of the eol-1 and drh-1 pathway from mitochondrial dysfunction to enhanced RNA interference and antiviral activity is a key output from mitochondria for anti-aging. abstract: RNA interference (RNAi) is an antiviral pathway common to many eukaryotes that detects and cleaves foreign nucleic acids. In mammals, mitochondrially localized proteins such as MAVS, RIG-I, and MDA5 mediate antiviral responses. Here, we report that mitochondrial dysfunction in Caenorhabditis elegans activates RNAi-directed silencing via induction of a pathway homologous to the mammalian RIG-I helicase viral response pathway. The induction of RNAi also requires the conserved RNA decapping enzyme EOL-1/DXO. The transcriptional induction of eol-1 requires DRH-1 as well as the mitochondrial unfolded protein response (UPRmt). Upon mitochondrial dysfunction, EOL-1 is concentrated into foci that depend on the transcription of mitochondrial RNAs that may form dsRNA, as has been observed in mammalian antiviral responses. The enhanced RNAi triggered by mitochondrial dysfunction contributes to the increase in longevity that is induced by mitochondrial dysfunction. url: https://doi.org/10.1101/2020.06.05.136978 doi: 10.1101/2020.06.05.136978 id: cord-102370-5uy8dq18 author: Marano, Jeffrey M. title: Rolling Circle Amplification is a high fidelity and efficient alternative to plasmid preparation for the rescue of infectious clones date: 2020-06-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Alphaviruses (genus Alphavirus; family Togaviridae) are a medically relevant family of viruses that include chikungunya virus, Eastern equine encephalitis virus, and the emerging Mayaro virus. Infectious cDNA clones of these viruses are necessary molecular tools to understand viral biology and to create effective vaccines. The traditional approach to rescuing virus from an infectious cDNA clone requires propagating large amounts of plasmids in bacteria, which can result in unwanted mutations in the viral genome due to bacterial toxicity or recombination and requires specialized equipment and knowledge to propagate the bacteria. Here, we present an alternative to the bacterial-based plasmid platform that uses rolling circle amplification (RCA), an in vitro technology that amplifies plasmid DNA using only basic equipment. We demonstrate that the use of RCA to amplify plasmid DNA is comparable to the use of a midiprepped plasmid in terms of viral yield, albeit with a slight delay in virus recovery kinetics. RCA, however, has lower cost and time requirements and amplifies DNA with high fidelity and with no chance of unwanted mutations due to toxicity. We show that sequential RCA reactions do not introduce mutations into the viral genome and, thus, can replace the need for glycerol stocks or bacteria entirely. These results indicate that RCA is a viable alternative to traditional plasmid-based approaches to viral rescue. Importance The development of infectious cDNA clones is critical to studying viral pathogenesis and for developing vaccines. The current method for propagating clones in bacteria is limited by the toxicity of the viral genome within the bacterial host, resulting in deleterious mutations in the viral genome, which can only be detected through whole-genome sequencing. These mutations can attenuate the virus, leading to lost time and resources and potentially confounding results. We have developed an alternative method of preparing large quantities of DNA that can be directly transfected to recover infectious virus without the need for bacteria by amplifying the infectious cDNA clone plasmid using rolling circle amplification (RCA). Our results indicate that viral rescue from an RCA product produces a viral yield equal to bacterial-derived plasmid DNA, albeit with a slight delay in replication kinetics. The RCA platform, however, is significantly more cost and time-efficient compared to traditional approaches. When the simplicity and costs of RCA are combined, we propose that a shift to an RCA platform will benefit the field of molecular virology and could have significant advantages for recombinant vaccine production. url: https://doi.org/10.1101/2020.06.22.165241 doi: 10.1101/2020.06.22.165241 id: cord-103105-iqjksoim author: Marinaik, Chandranaik B. title: Programming Multifaceted Pulmonary T-Cell Immunity by Combination Adjuvants date: 2020-07-10 words: 7343.0 sentences: 406.0 pages: flesch: 55.0 cache: ./cache/cord-103105-iqjksoim.txt txt: ./txt/cord-103105-iqjksoim.txt summary: An acrylic acid-based adjuvant (ADJ), in combination with TLR agonists glucopyranosyl lipid adjuvant (GLA) or CpG promoted mucosal imprinting but engaged distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Further, these studies provided the first glimpse of the evolution of T-cell responses to adjuvanted vaccines in the lungs to define the quantitative, phenotypic and functional attributes of mucosal effector/memory CD8 and CD4 T cells that are associated with effective viral control in the lungs, and protection against H1N1 and H5N1 influenza infections. Studies to determine the transcriptional basis for the disparate differentiation of effector CD8 T cells in different adjuvant groups showed that the expressions of T-bet, IRF-4 and BATF were substantially greater in ADJ and ADJ+CpG groups, compared to GLA and ADJ+GLA groups ( Fig. 1D) . abstract: Induction of protective mucosal T-cell memory remains a formidable challenge to vaccinologists. Using a novel adjuvant strategy that elicits unusually potent CD8 and CD4 T-cell responses, we have defined the tenets of vaccine-induced pulmonary T-cell immunity. An acrylic acid-based adjuvant (ADJ), in combination with TLR agonists glucopyranosyl lipid adjuvant (GLA) or CpG promoted mucosal imprinting but engaged distinct transcription programs to drive different degrees of terminal differentiation and disparate polarization of TH1/TC1/TH17/TC17 effector/memory T cells. Combination of ADJ with GLA, but not CpG, dampened TCR signaling, mitigated terminal differentiation of effectors and enhanced the development of CD4 and CD8 TRM that protected against H1N1 and H5N1 influenza viruses. Mechanistically, vaccine-elicited CD4 T cells played a vital role in optimal programming of CD8 TRM and anti-viral immunity. Taken together, these findings provide new insights into vaccine-induced multi-faceted mucosal T-cell immunity with significant implications in the development of vaccines against respiratory pathogens. One Sentence Summary Adjuvants Induce Multipronged T-Cell Immunity in the Respiratory Tract. url: https://doi.org/10.1101/2020.07.10.197459 doi: 10.1101/2020.07.10.197459 id: cord-263970-9w6ciglv author: Marquez-Miranda, Valeria title: Analysis of SARS-CoV-2 ORF3a structure reveals chloride binding sites date: 2020-10-22 words: 2882.0 sentences: 166.0 pages: flesch: 53.0 cache: ./cache/cord-263970-9w6ciglv.txt txt: ./txt/cord-263970-9w6ciglv.txt summary: SARS-CoV-2 ORF3a is believed to form ion channels, which may be involved in the modulation of virus release, and has been implicated in various cellular processes like the up-regulation of fibrinogen expression in lung epithelial cells, downregulation of type 1 interferon receptor, caspase-dependent apoptosis, and increasing IFNAR1 ubiquitination. Here we used this dimeric structure to perform full atom molecular dynamic simulations and electrostatic potential calculations to ask questions concerning the dimers'' stability and whether ions could be populating specific regions of the channel. To assess the impact of the ion occupancies described above, we obtained the electrostatic potential maps for the ORF3a channel for the initial configuration, and the last frame, at the end of a trajectory of 500 ns of the molecular dynamics simulations, by employing the Poison-Boltzmann approach implemented in the APBS package [12] . This analysis shows that the entry of Cl-ions through the inter-subunit tunnel into the central polar cavity and the accumulation of K+ ions at the cytosolic domain''s surface changed the channel''s electrostatic profile. abstract: SARS-CoV-2 ORF3a is believed to form ion channels, which may be involved in the modulation of virus release, and has been implicated in various cellular processes like the up-regulation of fibrinogen expression in lung epithelial cells, downregulation of type 1 interferon receptor, caspase-dependent apoptosis, and increasing IFNAR1 ubiquitination. ORF3a assemblies as homotetramers, which are stabilized by residue C133. A recent cryoEM structure of a homodimeric complex of ORF3a has been released. A lower-resolution cryoEM map of the tetramer suggests two dimers form it, arranged side by side. The dimer’s cryoEM structure revealed that each protomer contains three transmembrane helices arranged in a clockwise configuration forming a six helices transmembrane domain. This domain’s potential permeation pathway has six constrictions narrowing to about 1 Å in radius, suggesting the structure solved is in a closed or inactivated state. At the cytosol end, the permeation pathway encounters a large and polar cavity formed by multiple beta strands from both protomers, which opens to the cytosolic milieu. We modeled the tetramer following the arrangement suggested by the low-resolution tetramer cryoEM map. Molecular dynamics simulations of the tetramer embedded in a membrane and solvated with 0.5 M of KCl were performed. Our simulations show the cytosolic cavity is quickly populated by both K+ and Cl-, yet with different dynamics. K+ ions moved relatively free inside the cavity without forming proper coordination sites. In contrast, Cl- ions enter the cavity, and three of them can become stably coordinated near the intracellular entrance of the potential permeation pathway by an inter-subunit network of positively charged amino acids. Consequently, the central cavity’s electrostatic potential changed from being entirely positive at the beginning of the simulation to more electronegative at the end. url: https://www.ncbi.nlm.nih.gov/pubmed/33106803/ doi: 10.1101/2020.10.22.349522 id: cord-102231-cquxqbc2 author: Martinez, Xavier title: FAIR sharing of molecular visualization experiences: from pictures in the cloud to collaborative virtual reality exploration in immersive 3D environments date: 2020-08-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Motivated by the current Covid-19 pandemic that has spurred a substantial flow of structural data we describe how molecular visualization experiences can be used to make these datasets accessible to a broad audience. Using a variety of technology vectors related to the cloud, 3D- and virtual reality gear, we examine how to share curated visualizations of structural biology, modeling and/or bioinformatics datasets for interactive and collaborative exploration. We discuss F.A.I.R. as overarching principle for sharing such visualizations. We provide four initial example scenes related to recent Covid-19 structural data together with a ready-to-use (and share) implementation in the UnityMol software. Synopsis Visualization renders structural molecular data accessible to a broad audience. We describe an approach to share molecular visualization experiences based on FAIR principles. Our workflow is exemplified with recent Covid-19 related data. url: https://doi.org/10.1101/2020.08.27.270140 doi: 10.1101/2020.08.27.270140 id: cord-313571-umcbulcw author: Martínez-Murcia, Antonio title: In silico design and validation of commercial kit GPS™ CoVID-19 dtec-RT-qPCR Test under criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012 date: 2020-05-05 words: 1189.0 sentences: 85.0 pages: flesch: 54.0 cache: ./cache/cord-313571-umcbulcw.txt txt: ./txt/cord-313571-umcbulcw.txt summary: title: In silico design and validation of commercial kit GPS™ CoVID-19 dtec-RT-qPCR Test under criteria of UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012 Background The Corona Virus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has become a serious infectious disease affecting human health worldwide and rapidly declared a pandemic by WHO. Objectives A few days later, when additional SARS-CoV-2 genome were retrieved, the kit GPS™ CoVID-19 dtec-RT-qPCR Test was designed to provide a highly specific detection method and commercially available worldwide. Results The GPS™ RT-qPCR primers and probe showed the highest number of mismatches with the closet related non-SARS-CoV-2 coronavirus, including some indels. As the number of genomes available rapidly expanded during last January, the GPS™ CoVID-19 230 dtec-RT-qPCR Test was based on a more specific target for SARS-CoV-2 detection, being this 231 company one of the pioneers marketing a PCR-kit for the CoVID-19 worldwide. abstract: Background The Corona Virus Disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has become a serious infectious disease affecting human health worldwide and rapidly declared a pandemic by WHO. Early, several RT-qPCR were designed by using only the first SARS-CoV-2 genome sequence. Objectives A few days later, when additional SARS-CoV-2 genome were retrieved, the kit GPS™ CoVID-19 dtec-RT-qPCR Test was designed to provide a highly specific detection method and commercially available worldwide. The kit was validated following criteria recommended by the UNE/EN ISO 17025:2005 and ISO/IEC 15189:2012. Methods The present study approached the in silico specificity of the GPS™ CoVID-19 dtec-RT-qPCR Test and RT-qPCR designs currently published. The empirical validation parameters specificity (inclusivity/exclusivity), quantitative phase analysis (10-106 copies), reliability (repeatability/reproducibility) and sensitivity (detection/quantification limits) were evaluated for a minimum of 10-15 assays. Diagnostic validation was achieved by two independent reference laboratories, the Instituto de Salud Carlos III (ISCIII), (Madrid, Spain) and the Public Health England (PHE; Colindale, London, UK). Results The GPS™ RT-qPCR primers and probe showed the highest number of mismatches with the closet related non-SARS-CoV-2 coronavirus, including some indels. The kits passed all parameters of validation with strict acceptance criteria. Results from reference laboratories 100% correlated with these obtained by suing reference methods and received an evaluation with 100% of diagnostic sensitivity and specificity. Conclusions The GPS™ CoVID-19 dtec-RT-qPCR Test, available with full analytical and diagnostic validation, represents a case of efficient transfer of technology being successfully used since the pandemic was declared. The analysis suggested the GPS™ CoVID-19 dtec-RT-qPCR Test is the more exclusive by far. url: https://doi.org/10.1101/2020.04.27.065383 doi: 10.1101/2020.04.27.065383 id: cord-102189-wo9gg7nx author: Mathew, Nimitha R. title: Single cell BCR and transcriptome analysis after respiratory virus infection reveals spatiotemporal dynamics of antigen-specific B cell responses date: 2020-08-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: B cell responses are a critical component of anti-viral immunity. However, a comprehensive picture of antigen-specific B cell responses, differentiation, clonal proliferation and dynamics in different organs after infection is lacking. Here, we combined single-cell RNA sequencing with single-cell B cell receptor (BCR) characterization of antigen-specific cells in the draining lymph nodes, spleen and lungs after influenza infection. We identify several novel B cell subpopulations forming after infection and find organ-specific differences that persist over the course of the response. We discover important transcriptional differences between memory cells in lungs and lymphoid organs and describe organ-restricted clonal expansion. Strikingly, by combining BCR mutational analysis, monoclonal antibody expression and affinity measurements we find no differences between germinal center (GC)-derived memory and plasmacells, at odds with an affinity-based selection model. By linking antigen-recognition with transcriptional programming, clonal-proliferation and differentiation, these finding provide important advances in our understanding of antiviral B cell immunity. url: https://doi.org/10.1101/2020.08.24.264069 doi: 10.1101/2020.08.24.264069 id: cord-271971-rstmd0va author: Matsumura, Yasufumi title: Comparison of 12 molecular detection assays for SARS-CoV-2 date: 2020-06-25 words: 1203.0 sentences: 74.0 pages: flesch: 60.0 cache: ./cache/cord-271971-rstmd0va.txt txt: ./txt/cord-271971-rstmd0va.txt summary: We compared 12 molecular diagnostic assays, including 8 commercial kits using 155 respiratory samples (65 nasopharyngeal swabs, 45 oropharyngeal swabs, and 45 sputum) collected at 2 Japanese hospitals. Real-time RT-PCRs 54 were performed using N1, N2, and RNaseP (RP) internal control assays developed by the (4) (with/without EAV), N and E assays developed by Charité in Germany (1) (Corman) 59 with TaqPath™ 1-Step RT-qPCR Master Mix, CG (Thermo Fisher Scientific). In this study, to 79 ensure the presence of SARS-CoV-2 RNA and to avoid false-positives, a sample was 80 defined as positive when positive test results were obtained for more than one genetic 81 locus and assay and the others were defined as negative. 166 Different from multiplex assays that incorporate internal controls such as Roche, Thermo, 167 or BGI kits, this approach needs extra reagents, time, and space in a reaction plate but 168 can be combined with other in-house assays (NIID N2 or Corman E) without any 169 modification. abstract: Molecular testing for SARS-CoV-2 is the mainstay for accurate diagnosis of the infection, but the diagnostic performances of available assays have not been defined. We compared 12 molecular diagnostic assays, including 8 commercial kits using 155 respiratory samples (65 nasopharyngeal swabs, 45 oropharyngeal swabs, and 45 sputum) collected at 2 Japanese hospitals. Sixty-eight samples were positive for more than one assay and one genetic locus and were defined as true positive samples. All the assays showed a specificity of 100% (95% confidence interval, 95.8 to 100). The N2 assay kit of the US Centers for Disease Control and Prevention (CDC) and the N2 assay of the Japanese National Institute of Infectious Disease (NIID) were the most sensitive assays with 100% sensitivity (95% confidence interval, 94.7 to 100), followed by the CDC N1 kit, E assay by Corman, and NIID N2 assay multiplex with internal control reactions. These assays are reliable as first-line molecular assays in laboratories when combined with appropriate internal control reactions. url: https://doi.org/10.1101/2020.06.24.170332 doi: 10.1101/2020.06.24.170332 id: cord-336793-9bbyu1qx author: Matsuyama, Shutoku title: The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells date: 2020-08-24 words: 709.0 sentences: 48.0 pages: flesch: 62.0 cache: ./cache/cord-336793-9bbyu1qx.txt txt: ./txt/cord-336793-9bbyu1qx.txt summary: title: The inhaled steroid ciclesonide blocks SARS-CoV-2 RNA replication by targeting viral replication-transcription complex in culture cells We screened steroid compounds to obtain a drug expected to block host inflammatory responses and MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in non-structural protein 3 (nsp3) or nsp4. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients. In the present study, we found that an inhaled corticosteroid, ciclesonide suppresses replication of coronaviruses, including beta-coronaviruses (MHV-2, MERS-CoV, SARS-CoV, and SARS-CoV-2) and an alpha-coronavirus (HCoV-229E) in cultured cells. The inhaled corticosteroid ciclesonide blocks coronavirus RNA replication by targeting viral abstract: We screened steroid compounds to obtain a drug expected to block host inflammatory responses and MERS-CoV replication. Ciclesonide, an inhaled corticosteroid, suppressed replication of MERS-CoV and other coronaviruses, including SARS-CoV-2, the cause of COVID-19, in cultured cells. The effective concentration (EC90) of ciclesonide for SARS-CoV-2 in differentiated human bronchial tracheal epithelial cells was 0.55 μM. Ciclesonide inhibited formation of double membrane vesicles, which anchor the viral replication-transcription complex in cells. Eight consecutive passages of 43 SARS-CoV-2 isolates in the presence of ciclesonide generated 15 resistant mutants harboring single amino acid substitutions in non-structural protein 3 (nsp3) or nsp4. Of note, ciclesonide still suppressed replication of all these mutants by 90% or more, suggesting that these mutants cannot completely overcome ciclesonide blockade. These observations indicate that the suppressive effect of ciclesonide on viral replication is specific to coronaviruses, highlighting it as a candidate drug for the treatment of COVID-19 patients. Importance The outbreak of SARS-CoV-2, the cause of COVID-19, is ongoing. To identify the effective antiviral agents to combat the disease is urgently needed. In the present study, we found that an inhaled corticosteroid, ciclesonide suppresses replication of coronaviruses, including beta-coronaviruses (MHV-2, MERS-CoV, SARS-CoV, and SARS-CoV-2) and an alpha-coronavirus (HCoV-229E) in cultured cells. The inhaled ciclesonide is safe; indeed, it can be administered to infants at high concentrations. Thus, ciclesonide is expected to be a broad-spectrum antiviral drug that is effective against many members of the coronavirus family. It could be prescribed for the treatment of MERS, and COVID-19. url: https://doi.org/10.1101/2020.08.22.258459 doi: 10.1101/2020.08.22.258459 id: cord-103914-ppgx7mci author: Maughan, Elizabeth F. title: Cell-intrinsic differences between human airway epithelial cells from children and adults date: 2020-04-20 words: 8186.0 sentences: 419.0 pages: flesch: 47.0 cache: ./cache/cord-103914-ppgx7mci.txt txt: ./txt/cord-103914-ppgx7mci.txt summary: Here, we perform bulk RNA sequencing studies in laser-capture microdissected whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We found no significant differences in the proportion of cells in these three cellular compartments in paediatric and adult biopsies either by immunohistochemistry ( Figure 1A /1B), or by assessing basal, mucosecretory or ciliated cellassociated gene expression (Table S2 ) in bulk RNA sequencing in which we had laser-capture microdissected the whole epithelium ( Figure 1C ; Figure S1 ). Analysing this laser-capture microdissected whole epithelium RNA sequencing dataset using DESeq2 (Love et al., 2014) with a false discovery rate (FDR) of 1% and log2 fold change threshold of 1.2, we identified 37 genes with significant differential expression between paediatric and adult donors of which 17 were upregulated in adults and 20 were expressed at higher levels in children ( Figure 2A ; Table S3 ). abstract: The airway epithelium is a key protective barrier whose integrity is preserved by the self-renewal and differentiation of basal progenitor cells. Epithelial cells are central to the pathogenesis of multiple lung diseases. In chronic diseases, increasing age is a principle risk factor. In acute diseases, such as COVID-19, children suffer less severe symptoms than adults and have a lower rate of mortality. Few studies have explored differences between airway epithelial cells in children and adults to explain this age dependent variation in diseases. Here, we perform bulk RNA sequencing studies in laser-capture microdissected whole epithelium, FACS-sorted basal cells and cultured basal cells, as well as in vitro cell proliferation experiments, to address the intrinsic molecular differences between paediatric and adult airway basal cells. We find that, while the cellular composition of the paediatric and adult tracheobronchial epithelium is broadly similar, in cell culture, paediatric airway epithelial cells displayed higher colony forming ability, better in vitro growth and outcompeted adult cells in competitive proliferation assays. In RNA sequencing experiments, we observed potentially important differences in airway epithelial gene expression between samples from children and adults. However, genes known to be associated with SARS-CoV-2 infection were not differentially expressed between children and adults. Our results chart cell-intrinsic differences in transcriptional profile and regenerative capacity between proximal airway epithelial cells of children and adults. url: https://doi.org/10.1101/2020.04.20.027144 doi: 10.1101/2020.04.20.027144 id: cord-103157-xe5ccw9j author: Mayer, David title: Developing and Deploying a Scalable Computing Platform to Support MOOC Education in Clinical Data Science date: 2020-08-27 words: 4322.0 sentences: 222.0 pages: flesch: 53.0 cache: ./cache/cord-103157-xe5ccw9j.txt txt: ./txt/cord-103157-xe5ccw9j.txt summary: In response to these challenges we sought to create a hosted computing platform that would both manage student access to restricted materials and accommodate the unique challenges posed by MOOCs. The primary goal of developing the computing platform was to create a system that would allow instructors to restrict and monitor access to sensitive clinical data to only those students who had signed required data use agreements. New students are assigned a unique student id number, provisioned a linux user account on the Computing server (which is linked to their Google account), added to a private Google Group that has been assigned the appropriate IAM roles for accessing course BigQuery datasets, and a platform expiration date calculated (~6mo). We have created a computing platform to support clinical data science MOOC education that has been scalable, globally available, secure, privacy preserving, and generally supported independent access by a large number of students. abstract: One of the challenges of teaching applied data science courses is managing individual students’ local computing environment. This is especially challenging when teaching massively open online courses (MOOCs) where students come from across the globe and have a variety of access to and types of computing systems. There are additional challenges with using sensitive health information for clinical data science education. Here we describe the development and performance of a computing platform developed to support a series of MOOCs in clinical data science. This platform was designed to restrict and log all access to health datasets while also being scalable, accessible, secure, privacy preserving, and easy to access. Over the 19 months the platform has been live it has supported the computation of more than 2300 students from 101 countries. url: https://doi.org/10.1101/2020.08.27.270009 doi: 10.1101/2020.08.27.270009 id: cord-103542-mf721oa9 author: Mazhari, Ramin title: A comparison of non-magnetic and magnetic beads for measuring IgG antibodies against P. vivax antigens in a multiplexed bead-based assay using Luminex® technology (Bio-Plex® 200 or MAGPIX®) date: 2020-08-10 words: 1326.0 sentences: 72.0 pages: flesch: 52.0 cache: ./cache/cord-103542-mf721oa9.txt txt: ./txt/cord-103542-mf721oa9.txt summary: Multiplexed bead-based assays that use Luminex xMAP® technology have become popular for measuring antibodies against proteins of interest in many fields, including malaria and more recently SARS-CoV-2/COVID-19. Our external validation indicated that results generated in different laboratories using the same coupled beads are also highly comparable, particularly if a reference standard curve is used. To be able to measure all plasma 123 samples at the same dilution, we optimized all protein concentrations by generating a log-linear 124 standard curve with a positive control plasma pool from immune PNG donors (high responders to 125 Plasmodium antigens). Optimization of 374 a magnetic bead-based assay (MAGPIX((R))-Luminex) for immune surveillance of exposure to 375 malaria using multiple Plasmodium antigens and sera from different endemic settings Comparison of non-404 magnetic and magnetic beads multiplex assay for assessment of Plasmodium falciparum 405 antibodies abstract: Multiplexed bead-based assays that use Luminex xMAP® technology have become popular for measuring antibodies against proteins of interest in many fields, including malaria and more recently SARS-CoV-2/COVID-19. There are currently two formats that are widely used: non-magnetic beads or magnetic beads. Data is lacking regarding the comparability of results obtained using these two types of beads, and for assays run on different instruments. Whilst non-magnetic beads can only be run on flow-based instruments (such as the Luminex® 100/200™ or Bio-Plex® 200), magnetic beads can be run on both these and the newer MAGPIX® instruments. In this study we utilized a panel of purified recombinant Plasmodium vivax proteins and samples from malaria-endemic areas to measure P. vivax-specific IgG responses using different combinations of beads and instruments. We directly compared: i) non-magnetic versus magnetic beads run on a Bio-Plex® 200, ii) magnetic beads run on the Bio-Plex® 200 versus MAGPIX® and iii) non-magnetic beads run on a Bio-Plex® 200 versus magnetic beads run on the MAGPIX®. We also performed an external validation of our optimized assay. We observed that IgG antibody responses, measured against our panel of P. vivax proteins, were strongly correlated in all three of our comparisons, however higher amounts of protein were required for coupling to magnetic beads. Our external validation indicated that results generated in different laboratories using the same coupled beads are also highly comparable, particularly if a reference standard curve is used. url: https://doi.org/10.1101/2020.08.10.243980 doi: 10.1101/2020.08.10.243980 id: cord-313795-jr3n3uo9 author: McAuley, Julie L. title: Liquid chalk is an antiseptic against SARS-CoV-2 and influenza A respiratory viruses date: 2020-11-02 words: 1411.0 sentences: 85.0 pages: flesch: 56.0 cache: ./cache/cord-313795-jr3n3uo9.txt txt: ./txt/cord-313795-jr3n3uo9.txt summary: We investigated whether liquid chalk is an antiseptic against highly pathogenic human viruses including, SARS-CoV-2, influenza virus and noroviruses. We observed that addition of chalk before or after virus contact lead to a significant reduction on recovery of infectious SARS-CoV-2 and influenza but had little impact on norovirus. To further our study, we also tested the antiviral effect of Liquid Chalk against another 155 highly infectious and pathogenic respiratory viral pathogen IAV. 157 As can be observed in Figure 2 , all four Liquid Chalk products were effective in restricting the 158 recovery of IAV compared to SARS-CoV-2. transmission of SARS-CoV-2 (the 52 causative agent of the COVID-19 pandemic), influenza A virus (H1N1) (IAV) and norovirus, 53 using the surrogate model of mouse norovirus As a comparator, we also investigated the ability of Liquid Chalk to inactivate another 178 highly infectious viral pathogen, norovirus. abstract: The COVID-19 pandemic has impacted and enforced significant restrictions within our societies, including the attendance of the public and professional athletes in gyms. Liquid chalk is a commonly used accessories in gyms and is comprised of magnesium carbonate and alcohol that quickly evaporates on the hands to leave a layer of dry chalk. We investigated whether liquid chalk is an antiseptic against highly pathogenic human viruses including, SARS-CoV-2, influenza virus and noroviruses. Chalk was applied before or after virus inoculum and recovery of infectious virus was determined to mimic the use in the gym. We observed that addition of chalk before or after virus contact lead to a significant reduction on recovery of infectious SARS-CoV-2 and influenza but had little impact on norovirus. These observations suggest that the use and application of liquid chalk can be an effective and suitable antiseptic for major sporting events, such as the Olympic Games. url: https://doi.org/10.1101/2020.11.02.364661 doi: 10.1101/2020.11.02.364661 id: cord-102770-t4zgph9k author: McComb, Scott title: Fine Molecular Tuning of Chimeric Antigen Receptors through Hinge Length Optimization date: 2020-10-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Background Chimeric antigen receptor (CAR) technology has revolutionized the treatment of B-cell malignancies and steady progress is being made towards CAR-immunotherapies for solid tumours. In the context of CARs targeting antigens which are commonly overexpressed in cancer but also expressed at lower levels in normal tissues, such as epidermal growth factor family receptors EGFR or HER2, it is imperative that any targeting strategy consider the potential for on-target off-tumour toxicity. Molecular optimization of the various protein domains of CARs can be used to increase the tumour selectivity. Method Herein, we utilize high-throughput CAR screening to identify a novel camelid single-domain antibody CAR (sdCAR) targeting human epidermal growth factor (EGFR) with high EGFR-specific activity. To further optimize the target selectivity of this EGFR-sdCAR, we performed progressive N-terminal single amino acid truncations of an extended human CD8 hinge domain [(G4S)3GG-45CD8h] to improve selectivity for EGFR-overexpressing cells. We also make direct comparison of varying hinge domains in scFv-based CARs targeting EGFR-family tumour associated antigens EGFRvIII and HER2. Results Through comparison of various hinge-truncated scFv- and sdAb-based CARs, we show that the CAR hinge/spacer domain plays varying roles in modifying CAR signaling depending upon target epitope location. For membrane-proximal epitopes, hinge truncation by even a single amino acid resulted in fine control of CAR signaling strength. Hinge-modified CARs showed consistent and predictable signaling in Jurkat-CAR cells and primary human CAR-T cells in vitro and in vivo. Conclusions Overall, these results indicate that membrane-proximal epitope targeting CARs can be optimized through hinge length tuning for improved target selectivity and therapeutic function. Graphical Abstract url: https://doi.org/10.1101/2020.10.30.360925 doi: 10.1101/2020.10.30.360925 id: cord-314445-4cb4a9r5 author: McNamara, Ryan P. title: High-density amplicon sequencing identifies community spread and ongoing evolution of SARS-CoV-2 in the Southern United States date: 2020-06-19 words: 1960.0 sentences: 131.0 pages: flesch: 53.0 cache: ./cache/cord-314445-4cb4a9r5.txt txt: ./txt/cord-314445-4cb4a9r5.txt summary: This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. The current COVID-19 pandemic is an urgent public health emergency with over 112,000 deaths in the United States (U.S.) alone. At a CP ≥35 most positive samples still yielded reads that mapped to the target genome 227 and thus allowed detection of SARS-CoV-2 sequences; however, the results were less consistent, 228 and coverage was more variable. In sum, this study generated exhaustive SNV information representing the introduction and 325 spread of SARS-CoV-2 across a suburban low-density area in the Southern U.S. All samples were 326 from symptomatic cases and the majority of genomes clustered with variants that predominate the 327 outbreak in the U.S., rather than Europe or China. abstract: SARS-CoV-2 is constantly evolving. Prior studies have focused on high case-density locations, such as the Northern and Western metropolitan areas in the U.S. This study demonstrates continued SARS-CoV-2 evolution in a suburban Southern U.S. region by high-density amplicon sequencing of symptomatic cases. 57% of strains carried the spike D614G variant. The presence of D614G was associated with a higher genome copy number and its prevalence expanded with time. Four strains carried a deletion in a predicted stem loop of the 3’ untranslated region. The data are consistent with community spread within the local population and the larger continental U.S. No strain had mutations in the target sites used in common diagnostic assays. The data instill confidence in the sensitivity of current tests and validate “testing by sequencing” as a new option to uncover cases, particularly those not conforming to the standard clinical presentation of COVID-19. This study contributes to the understanding of COVID-19 by providing an extensive set of genomes from a non-urban setting and further informs vaccine design by defining D614G as a dominant and emergent SARS-CoV-2 isolate in the U.S. url: https://doi.org/10.1101/2020.06.19.161141 doi: 10.1101/2020.06.19.161141 id: cord-103757-fed21fhu author: McPherson, Malinda J. title: Time-dependent discrimination advantages for harmonic sounds suggest efficient coding for memory date: 2020-10-15 words: 13309.0 sentences: 653.0 pages: flesch: 48.0 cache: ./cache/cord-103757-fed21fhu.txt txt: ./txt/cord-103757-fed21fhu.txt summary: The similarity in performance between harmonic and inharmonic tones without a delay provides circumstantial evidence that listeners are computing changes in the same way for both types of stimuli, presumably using a representation of the spectrum in both cases. We examined the relationship between pitch perception and memory by measuring the discrimination of harmonic and inharmonic sounds with and without a time delay between stimuli. The results provide evidence for two distinct mechanisms for pitch discrimination, reveal the constraints that determine when they are used, and demonstrate a form of abstraction within the auditory system whereby the representations of memory differ in format from those used for rapid on-line judgments about sounds. We found consistent overall pitch discrimination advantages for musicians compared to non-musicians ( Supplementary Figures 1-3 ), but found no evidence that this benefit was specific to f0 representations: musicianship did not interact with the effects of inharmonicity or inter-stimulus delay. abstract: Perceptual systems have finite memory resources and must store incoming signals in compressed formats. To explore whether representations of a sound’s pitch might derive from this need for compression, we compared discrimination of harmonic and inharmonic sounds across delays. In contrast to inharmonic spectra, harmonic spectra can be summarized, and thus compressed, using their fundamental frequency (f0). Participants heard two sounds and judged which was higher. Despite being comparable for sounds presented back-to-back, discrimination was better for harmonic than inharmonic stimuli when sounds were separated in time, implicating memory representations unique to harmonic sounds. Patterns of individual differences (correlations between thresholds in different conditions) indicated that listeners use different representations depending on the time delay between sounds, directly comparing the spectra of temporally adjacent sounds, but transitioning to comparing f0s across delays. The need to store sound in memory appears to determine reliance on f0-based pitch, and may explain its importance in music, in which listeners must extract relationships between notes separated in time. url: https://doi.org/10.1101/2020.05.07.082511 doi: 10.1101/2020.05.07.082511 id: cord-104140-o46kvd0b author: McPherson, Malinda J. title: Harmonicity aids hearing in noise date: 2020-09-30 words: 9606.0 sentences: 533.0 pages: flesch: 51.0 cache: ./cache/cord-104140-o46kvd0b.txt txt: ./txt/cord-104140-o46kvd0b.txt summary: To explore whether harmonic frequency relations aid hearing of sounds in noise, we compared detection and discrimination of harmonic and inharmonic tones and spoken vowels embedded in noise. However, detection thresholds were substantially better for harmonic than inharmonic complex tones even though they each had 10 frequency components (significant differences in both sine and random phase conditions, Wilcoxon signed-rank test: sine phase: Z=6.97, p<.001; random phase: Z=6.83, p<.001). Specifically, it seemed plausible that being better able to separate tones from noise might help listeners discriminate successive tones at low SNRs. Using an adaptive procedure, we measured traditional up-down discrimination thresholds for Harmonic, Inharmonic, and Pure Tone conditions (Fig. 3a) at a range of SNRs. Participants. We replotted the pitch discrimination curves in terms of the SNR relative to the detection thresholds measured in Experiment 1 (-21.00 dB SNR, -19.77 dB SNR, -17.39 dB SNR, for Harmonic, Inharmonic and Pure Tone conditions, respectively, Fig. 2b, inset) . abstract: Hearing in noise is a core problem in audition, and a challenge for hearing-impaired listeners, yet the underlying mechanisms are poorly understood. We explored whether harmonic frequency relations, a signature property of many communication sounds, aid hearing in noise. We measured detection thresholds in noise for tones and speech synthesized to have harmonic or inharmonic spectra. Harmonic signals were consistently easier to detect than otherwise identical inharmonic signals. Harmonicity also improved discrimination of sounds in noise. In contrast to other documented effects of harmonicity, harmonic detection advantages were comparable in musicians and non-musicians. The results show that harmonicity is critical for hearing in noise, demonstrating a previously unappreciated aspect of auditory scene analysis. The consistency of the effect across synthetic and natural stimuli, as well as across musical expertise, suggests its importance in everyday hearing. url: https://doi.org/10.1101/2020.09.30.321000 doi: 10.1101/2020.09.30.321000 id: cord-103071-6cgih8o9 author: Mead, Benjamin E. title: High-throughput organoid screening enables engineering of intestinal epithelial composition date: 2020-04-28 words: 12408.0 sentences: 655.0 pages: flesch: 50.0 cache: ./cache/cord-103071-6cgih8o9.txt txt: ./txt/cord-103071-6cgih8o9.txt summary: Strikingly, in our screen we identify inhibitors of the nuclear exporter Xpo1 modulate stem cell fate commitment by inducing a pan-epithelial stress response combined with an interruption of mitogen signaling in cycling intestinal progenitors, thereby significantly increasing the abundance of Paneth cells independent of known WNT and Notch differentiation cues. Administration of KPT-330 below 160 nM for 6 days (NB higher concentrations proved toxic in primary screening) showed LYZ secretion increasing in a dose-dependent manner, with 160 nM of KPT-330 as the most effective dose among tested concentrations KPT-330 is a selective inhibitor of nuclear export (SINE); these molecules act by suppressing the Xpo1-regulated nuclear export of multiple proteins and mRNAs from the nucleus to the cytoplasm -including genes involved in stem cell maintenance and differentiation as well as inflammatory stress response (Sendino et al., 2018) . abstract: Barrier tissue epithelia play an essential role in maintaining organismal homeostasis, and changes in their cellular composition have been observed in multiple human diseases. Within the small intestinal epithelium, adult stem cells integrate diverse signals to regulate regeneration and differentiation, thereby establishing overall cellularity. Accordingly, directing stem cell differentiation could provide a tractable approach to alter the abundance or quality of specialized cells of the small intestinal epithelium, including the secretory Paneth, goblet, and enteroendocrine populations. Yet, to date, there has been a lack of suitable tools and rigorous approaches to identify biological targets and pharmacological agents that can modify epithelial composition to enable causal testing of disease-associated changes with novel therapeutic candidates. To empower the search for epithelia-modifying agents, we establish a first-of-its-kind high-throughput phenotypic organoid screen. We demonstrate the ability to screen thousands of samples and uncover biological targets and associated small molecule inhibitors which translate to in vivo. This approach is enabled by employing a functional, cell-type specific, scalable assay on an organoid model designed to represent the physiological cues of in vivo Paneth cell differentiation from adult intestinal stem cells. Further, we miniaturize and adapt the organoid culture system to enable automated plating and screening, thereby providing the ability to test thousands of samples. Strikingly, in our screen we identify inhibitors of the nuclear exporter Xpo1 modulate stem cell fate commitment by inducing a pan-epithelial stress response combined with an interruption of mitogen signaling in cycling intestinal progenitors, thereby significantly increasing the abundance of Paneth cells independent of known WNT and Notch differentiation cues. We extend our observation in vivo, demonstrating that oral administration of Xpo1 inhibitor KPT-330 at doses 1,000-fold lower than conventionally used in hematologic malignancies increases Paneth cell abundance. In total, we provide a framework to identify novel biological cues and therapeutic leads to rebalance intestinal stem cell differentiation and modulate epithelial tissue composition via high-throughput phenotypic screening in rationally-designed organoid model of differentiation. url: https://doi.org/10.1101/2020.04.27.063727 doi: 10.1101/2020.04.27.063727 id: cord-281679-xmbnpawj author: Meekins, David A. title: Susceptibility of swine cells and domestic pigs to SARS-CoV-2 date: 2020-08-16 words: 3402.0 sentences: 191.0 pages: flesch: 46.0 cache: ./cache/cord-281679-xmbnpawj.txt txt: ./txt/cord-281679-xmbnpawj.txt summary: In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Cats, hamsters, and ferrets are highly susceptible to SARS-CoV-2 infection, demonstrate varying clinical and pathological disease manifestations, readily transmit the virus to naïve animals, and mount a virusspecific immune response [22] [23] [24] [25] [26] [27] [28] . Pigs are therefore unlikely to play an important role in the COVID-19 pandemic as a virus reservoir or as a pre-clinical animal model to study SARS-CoV-2 pathogenesis or develop novel countermeasures. abstract: The emergence of SARS-CoV-2 has resulted in an ongoing global pandemic with significant morbidity, mortality, and economic consequences. The susceptibility of different animal species to SARS-CoV-2 is of concern due to the potential for interspecies transmission, and the requirement for pre-clinical animal models to develop effective countermeasures. In the current study, we determined the ability of SARS-CoV-2 to (i) replicate in porcine cell lines, (ii) establish infection in domestic pigs via experimental oral/intranasal/intratracheal inoculation, and (iii) transmit to co-housed naive sentinel pigs. SARS-CoV-2 was able to replicate in two different porcine cell lines with cytopathic effects. Interestingly, none of the SARS-CoV-2-inoculated pigs showed evidence of clinical signs, viral replication or SARS-CoV-2-specific antibody responses. Moreover, none of the sentinel pigs displayed markers of SARS-CoV-2 infection. These data indicate that although different porcine cell lines are permissive to SARS-CoV-2, five-week old pigs are not susceptible to infection via oral/intranasal/intratracheal challenge. Pigs are therefore unlikely to be significant carriers of SARS-CoV-2 and are not a suitable pre-clinical animal model to study SARS-CoV-2 pathogenesis or efficacy of respective vaccines or therapeutics. url: https://doi.org/10.1101/2020.08.15.252395 doi: 10.1101/2020.08.15.252395 id: cord-102502-hroxg2u1 author: Megremis, Spyridon title: Microbial and autoantibody immunogenic repertoires in TIF1γ autoantibody positive dermatomyositis date: 2020-03-26 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: We investigate the accumulated microbial and autoantigen antibody repertoire in adult-onset dermatomyositis patients sero-positive for TIF1γ (TRIM33) autoantibodies. We use an untargeted high-throughput approach which combines immunoglobulin disease-specific epitope-enrichment and identification of microbial and human antigens. Increased microbial diversity was observed in dermatomyositis. Viruses were over-represented and species of the Poxviridae family were significantly enriched. The autoantibodies identified recognised a large portion of the human proteome, including interferon regulated proteins; these proteins were clustered in specific biological processes. Apart from TRIM33, autoantibodies against eleven further TRIM proteins, including TRIM21, were identified. Some of these TRIM proteins shared epitope homology with specific viral species including poxviruses. Our data suggest antibody accumulation in dermatomyositis against an expanded diversity of microbial and human proteins and evidence of non-random targeting of specific signalling pathways. Our findings indicate that molecular mimicry and epitope spreading events may play a significant role in the pathogenesis of dermatomyositis. url: https://doi.org/10.1101/2020.03.25.007534 doi: 10.1101/2020.03.25.007534 id: cord-354315-yfn9vaan author: Meirson, Tomer title: Structural basis of SARS-CoV-2 spike protein induced by ACE2 date: 2020-05-24 words: 5190.0 sentences: 253.0 pages: flesch: 49.0 cache: ./cache/cord-354315-yfn9vaan.txt txt: ./txt/cord-354315-yfn9vaan.txt summary: This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The critical step in SARS-CoV-2 infection which involves the transition between a metastable prefusion state to a stable post-fusion state is triggered by binding to ACE2 which induces conformational changes in the RBD and the hinge region (Gui, et al., 2017; Pallesen, et al., 2017; Song, et al., 2018; Walls, et al., 2020) . To gain insights into the effects of ACE2 interaction on the S protein of SARS-COV-2, we analyzed the intramolecular structural variations in the bound versus the unbound-closed Numerous structures of the prefusion human CoV S proteins were determined at different states, and the key regions responsible for the interaction with the receptor were previously reported (Lan, et al., 2020; Shang, et al., 2020; Walls, et al., 2020; Wan, et al., 2020; Wrapp, et al., 2020; Yan, et al., 2020) . abstract: Motivation The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The viral spike (S) glycoprotein binds the receptor (angiotensin-converting enzyme 2) ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the distal receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unravelling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD. Results Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that κ-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the proximal hinge region. This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables us to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2. url: https://doi.org/10.1101/2020.05.24.113175 doi: 10.1101/2020.05.24.113175 id: cord-296268-kb7fgfaq author: Mendonça, Luiza title: SARS-CoV-2 Assembly and Egress Pathway Revealed by Correlative Multi-modal Multi-scale Cryo-imaging date: 2020-11-05 words: 2647.0 sentences: 161.0 pages: flesch: 57.0 cache: ./cache/cord-296268-kb7fgfaq.txt txt: ./txt/cord-296268-kb7fgfaq.txt summary: Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Understanding the genome 27 replication, assembly and egress of SARS-CoV-2, a multistage process that involves different 28 cellular compartments and the activity of many viral and cellular proteins, is critically Krios to identify each individual infected cell (39.2 % for MOI of 0.1 and 45.4% for MOI 124 0.5) where cryoET tilt series were collected at the cell periphery. The grids were then 125 transferred to a FIB/SEM dualbeam instrument and the same infected cells were subjected to 126 either serial cryoFIB/SEM volume imaging (Zhu et al., 2021) or cryoFIB milling of cellular 127 lamellae where additional cryoET tilt series were collected (Sutton et al., 2020) . abstract: Since the outbreak of the SARS-CoV-2 pandemic, there have been intense structural studies on purified recombinant viral components and inactivated viruses. However, investigation of the SARS-CoV-2 infection in the native cellular context is scarce, and there is a lack of comprehensive knowledge on SARS-CoV-2 replicative cycle. Understanding the genome replication, assembly and egress of SARS-CoV-2, a multistage process that involves different cellular compartments and the activity of many viral and cellular proteins, is critically important as it bears the means of medical intervention to stop infection. Here, we investigated SARS-CoV-2 replication in Vero cells under the near-native frozen-hydrated condition using a unique correlative multi-modal, multi-scale cryo-imaging approach combining soft X-ray cryo-tomography and serial cryoFIB/SEM volume imaging of the entire SARS-CoV-2 infected cell with cryo-electron tomography (cryoET) of cellular lamellae and cell periphery, as well as structure determination of viral components by subtomogram averaging. Our results reveal at the whole cell level profound cytopathic effects of SARS-CoV-2 infection, exemplified by a large amount of heterogeneous vesicles in the cytoplasm for RNA synthesis and virus assembly, formation of membrane tunnels through which viruses exit, and drastic cytoplasm invasion into nucleus. Furthermore, cryoET of cell lamellae reveals how viral RNAs are transported from double-membrane vesicles where they are synthesized to viral assembly sites; how viral spikes and RNPs assist in virus assembly and budding; and how fully assembled virus particles exit the cell, thus stablishing a model of SARS-CoV-2 genome replication, virus assembly and egress pathways. url: https://doi.org/10.1101/2020.11.05.370239 doi: 10.1101/2020.11.05.370239 id: cord-102908-sr7j8z9c author: Mersmann, Sophia F. title: Learning to count: determining the stoichiometry of bio-molecular complexes using fluorescence microscopy and statistical modelling date: 2020-07-24 words: 5244.0 sentences: 260.0 pages: flesch: 42.0 cache: ./cache/cord-102908-sr7j8z9c.txt txt: ./txt/cord-102908-sr7j8z9c.txt summary: We used differential binary labelling and statistical modelling to extract estimates of stoichiometry, our strategy is outlined in Figure 1 ; note that this approach can be generalised to apply to many other multi-component systems (i.e. how many protein x are found in assembly y?). As described above, our experimental design utilizes antibody labelled with spectrally distinct dyes allowing binary scoring of individual virus particles as positive if they interact with at least one Ab B molecule ( Figure 1 ). We have demonstrated quantitative analysis of 9C12 interaction with individual Adv particles ( Figure 3) ; we have confirmed that differential labelling of antibody does not bias binding ( Figure 4A & B) ; and that we could detect single molecules of 9C12 Biotin allowing discrimination of positive and negative AdV-9C12 complexes ( Figure 4C & D). However, using stoichiometric estimates to calibrate fluorescent data revealed population heterogeneity with a small proportion of virus particles binding ∼200 antibody molecules. abstract: Cellular biology occurs through myriad interactions between diverse molecular components, many of which assemble in to specific complexes. Various techniques can provide a qualitative survey of which components are found in a given complex. However, quantitative analysis of the absolute number of molecules within a complex (known as stoichiometry) remains challenging. Here we provide a novel method that combines fluorescence microscopy and statistical modelling to derive accurate molecular counts. We have devised a system in which a given biomolecule is differentially labelled with spectrally distinct fluorescent dyes (label A or B), which are then mixed such that B-labelled molecules are vastly outnumbered by those with label A. Complexes, containing this component, are then simply scored as either being positive or negative for label B. The frequency of positive complexes is directly related to the stoichiometry of interaction and molecular counts can be inferred by statistical modelling. We demonstrate this method using complexes of Adenovirus particles and monoclonal antibodies, achieving counts that are in excellent agreement with previous estimates. Beyond virology, this approach is readily transferable to other experimental systems and, therefore, provides a powerful tool for quantitative molecular biology. The statistical models used in our analysis are available here: https://github.com/sophiamersmann/molecular-counting, the raw data used for molecular counting can be found here: 10.5281/zenodo.3955142. url: https://doi.org/10.1101/2020.07.23.217745 doi: 10.1101/2020.07.23.217745 id: cord-334220-sqvfr31q author: Messina, Francesco title: Looking for pathways related to COVID-19 phenotypes: Confirmation of pathogenic mechanisms by SARS-CoV-2 - Host interactome date: 2020-11-03 words: 4218.0 sentences: 237.0 pages: flesch: 44.0 cache: ./cache/cord-334220-sqvfr31q.txt txt: ./txt/cord-334220-sqvfr31q.txt summary: The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. In SFigure For KEGG database the gene enrichment analysis on interactomes of NS7b, ORF1a, ORF3a and ORF8 showed pathway clusters highly significant and consistent with possible pathogenic mechanisms, such as the activation of the complement and of the coagulative cascade, (29) and the TGF-β-dominated immune response (30) . We identified different host response induced by specific proteins of SARS-CoV-2, underlining the important role of ORF3a and ORF8 in phenotypes of severe COVID-19 patients. abstract: In the last months, many studies have clearly described several mechanisms of SARS-CoV-2 infection at cell and tissue level. Host conditions and comorbidities were identified as risk factors for severe and fatal disease courses, but the mechanisms of interaction between host and SARS-CoV-2 determining the grade of COVID- 19 severity, are still unknown. We provide a network analysis on protein–protein interactions (PPI) between viral and host proteins to better identify host biological responses, induced by both whole proteome of SARS-CoV-2 and specific viral proteins. A host-virus interactome was inferred on published PPI, using an explorative algorithm (Random Walk with Restart) triggered by all the 28 proteins of SARS-CoV-2, or each single viral protein one-by-one. The functional analysis for all proteins, linked to many aspects of COVID-19 pathogenesis, allows to identify the subcellular districts, where SARS-CoV-2 proteins seem to be distributed, while in each interactome built around one single viral protein, a different response was described, underlining as ORF8 and ORF3a modulated cardiovascular diseases and pro-inflammatory pathways, respectively. Finally, an explorative network-based approach was applied to Bradykinin Storm, highlighting a possible direct action of ORF3a and NS7b to enhancing this condition. This network-based model for SARS-CoV-2 infection could be a framework for pathogenic evaluation of specific clinical outcomes. We identified possible host responses induced by specific proteins of SARS-CoV-2, underlining the important role of specific viral accessory proteins in pathogenic phenotypes of severe COVID-19 patients. url: https://doi.org/10.1101/2020.11.03.366666 doi: 10.1101/2020.11.03.366666 id: cord-271849-wxmr8eki author: Meysman, Pieter title: Tracking SARS-CoV-2 T cells with epitope-T-cell receptor recognition models date: 2020-09-09 words: 2924.0 sentences: 166.0 pages: flesch: 58.0 cache: ./cache/cord-271849-wxmr8eki.txt txt: ./txt/cord-271849-wxmr8eki.txt summary: In this paper, we demonstrate the use of machine learning to classify SARS-CoV-2 epitope specific T-cell clonotypes in T-cell receptor (TCR) sequencing data. We apply these models to public TCR data and show how they can be used to study T-cell longitudinal profiles in COVID-19 patients to characterize how the adaptive immune system reacts to the SARS-CoV-2 virus. No other epitopes present in TCRex (including the 49 non-SARS-CoV-2 models) were predicted to have a single TCR target within this data set. Once established, these models can be applied to any TCR repertoire data and thus can be used to study putative SARS-CoV-2 reactive T cells in the currently available COVID-19 data. In addition, using such models on longitudinal data reveals a potential difference in temporal dynamics between T cells predicted to react against epitopes that are unique to SARS-CoV-2 and those that are shared among other coronaviruses. abstract: Much is still not understood about the human adaptive immune response to SARS-CoV-2, the causative agent of COVID-19. In this paper, we demonstrate the use of machine learning to classify SARS-CoV-2 epitope specific T-cell clonotypes in T-cell receptor (TCR) sequencing data. We apply these models to public TCR data and show how they can be used to study T-cell longitudinal profiles in COVID-19 patients to characterize how the adaptive immune system reacts to the SARS-CoV-2 virus. Our findings confirm prior knowledge that SARS-CoV-2 reactive T-cell diversity increases over the course of disease progression. However our results show a difference between those T cells that react to epitope unique to SARS-CoV-2, which show a more prominent increase, and those T cells that react to epitopes common to other coronaviruses, which begin at a higher baseline. url: https://doi.org/10.1101/2020.09.09.289355 doi: 10.1101/2020.09.09.289355 id: cord-102704-wfuzk2dp author: Meza, Diana K. title: Predicting the presence and titer of rabies virus neutralizing antibodies from low-volume serum samples in low-containment facilities date: 2020-04-30 words: 3183.0 sentences: 192.0 pages: flesch: 43.0 cache: ./cache/cord-102704-wfuzk2dp.txt txt: ./txt/cord-102704-wfuzk2dp.txt summary: Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained. The binomial and log-normal models fit to 193 this data subset included only the fixed effect of the virus-infected N2A cell counts, but the random 194 effects were identical to those explained above (i.e. test date and field). A final distinction is that 316 instead of scoring microscope field or wells as virus positive or negative, the pmRFFIT predicts 317 serological status and RVNA titer from infected cell counts in a single serum dilution using statistical 318 abstract: Serology is a core component of the surveillance and management of viral zoonoses. Virus neutralization tests are a gold standard serological diagnostic, but requirements for large volumes of serum and high biosafety containment can limit widespread use. Here, focusing on Rabies lyssavirus, a globally important zoonosis, we developed a pseudotype micro-neutralization rapid fluorescent focus inhibition test (pmRFFIT) that overcomes these limitations. Specifically, we adapted an existing micro-neutralization test to use a green fluorescent protein–tagged murine leukemia virus pseudotype in lieu of pathogenic rabies virus, reducing the need for specialized reagents for antigen detection and enabling use in low-containment laboratories. We further used statistical analysis to generate rapid, quantitative predictions of the probability and titer of rabies virus neutralizing antibodies from microscopic imaging of neutralization outcomes. Using 47 serum samples from domestic dogs with neutralizing antibody titers estimated using the fluorescent antibody virus neutralization test (FAVN), pmRFFIT showed moderate sensitivity (78.79%) and high specificity (84.62%). Despite small conflicts, titer predictions were correlated across tests repeated on different dates both for dog samples (r = 0.93), and for a second dataset of sera from wild common vampire bats (r = 0.72, N = 41), indicating repeatability. Our test uses a starting volume of 3.5 μL of serum, estimates titers from a single dilution of serum rather than requiring multiple dilutions and end point titration, and may be adapted to target neutralizing antibodies against alternative lyssavirus species. The pmRFFIT enables high-throughput detection of rabies virus neutralizing antibodies in low-biocontainment settings and is suited to studies in wild or captive animals where large serum volumes cannot be obtained. url: https://doi.org/10.1101/2020.04.24.060095 doi: 10.1101/2020.04.24.060095 id: cord-103864-4kec8re4 author: Miao, Zhen title: Single cell resolution regulatory landscape of the mouse kidney highlights cellular differentiation programs and renal disease targets date: 2020-06-04 words: 1819.0 sentences: 113.0 pages: flesch: 39.0 cache: ./cache/cord-103864-4kec8re4.txt txt: ./txt/cord-103864-4kec8re4.txt summary: Here, we profiled open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms. Here, we reasoned that 474 single cell accessible chromatin information could be extremely useful to identify the cell type-475 specific enhancer regions and thereby the target cell type for the GWAS hits, however, such maps 476 have not been generated for the human kidney. 539 540 By performing massively parallel single cell profiling of chromatin state, we were able to define 541 the key regulatory logic for each kidney cell type by investigating cis-regulatory elements and TF-542 target gene interaction. 548 549 We also observed that the single cell open chromatin atlas was able to define more distinct cell 550 types even in the developing kidney compared to scRNA-seq analysis. abstract: Determining the epigenetic program that generates unique cell types in the kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profiled open chromatin and gene expression in developing and adult mouse kidneys at single cell resolution. We show critical reliance of gene expression on distal regulatory elements (enhancers). We define key cell type-specific transcription factors and major gene-regulatory circuits for kidney cells. Dynamic chromatin and expression changes during nephron progenitor differentiation demonstrated that podocyte commitment occurs early and is associated with sustained Foxl1 expression. Renal tubule cells followed a more complex differentiation, where Hfn4a was associated with proximal and Tfap2b with distal fate. Mapping single nucleotide variants associated with human kidney disease identified critical cell types, developmental stages, genes, and regulatory mechanisms. We provide a global single cell resolution view of chromatin accessibility of kidney development. The dataset is available via interactive public websites. url: https://doi.org/10.1101/2020.05.24.113910 doi: 10.1101/2020.05.24.113910 id: cord-102729-b1q7gbd6 author: Mickael, Alexandra title: Asip (Agouti-signaling protein) aggression gene regulate auditory processing genes in mice date: 2020-06-12 words: 4430.0 sentences: 281.0 pages: flesch: 48.0 cache: ./cache/cord-102729-b1q7gbd6.txt txt: ./txt/cord-102729-b1q7gbd6.txt summary: ASIP (nonagouti) gene plays a vital role in regulating the melanocortin GPCRs family function, and it is responsible for regulating aggression in mice. We found that ASIP KO in mice upregulates several genes controlling auditory function, including Phox2b, Mpk13, Fat2, Neurod2, Slc18a3, Gon4l Gbx2, Slc6a3(Dat1) Aldh1a7 Tyrp1 and Lbx1. In order to confirm that our mice model study would be representative of aggression hearing link, we conducted an evolutionary study that revealed that ASIP is negatively selected between mice and humans. When we analyzed RNA-seq for Asip ko mouse model we found that several genes controlling hearing were upregulated in the KO samples. We found these results reflected in the molecular pathway of melanocortin receptors 1 and 4, where their knocking out their negative agonist; Asip resulted in upregulating various hearing associated genes such as Fat2 among others. abstract: Covid-19 strategy of lockdown has affected the lives of millions. The strict actions to enclose the epidemic have exposed many households to inner tensions. Domestic violence has been reported to increase during the lockdown. However, the reasons for this phenomenon have not been thoroughly investigated. Melanocortin GPCRs family contribution to aggression is well documented. ASIP (nonagouti) gene plays a vital role in regulating the melanocortin GPCRs family function, and it is responsible for regulating aggression in mice. We conducted a selection analysis of ASIP. We found that it negatively purified from Shark to humans. In order to better asses the effect of this gene in mammals, we performed RNA-seq analysis of a knockout of an ASIP crisper-cas mouse model. We found that ASIP KO in mice upregulates several genes controlling auditory function, including Phox2b, Mpk13, Fat2, Neurod2, Slc18a3, Gon4l Gbx2, Slc6a3(Dat1) Aldh1a7 Tyrp1 and Lbx1. Interestingly, we found that Slc6a5, and Lamp5 as well as IL33, which are associated with startle disease, are also upregulated in response to knocking out ASIP. These findings are indicative of a direct autoimmune effect between aggression-associated genes and startle disease. Furthermore, in order to validate the link between aggression and auditory inputs processing. We conducted psychological tests of persons who experienced lockdown. We found that aggression has risen by 16 % during the lockdown. Furthermore, 3% of the subjects interviewed reported a change in their hearing abilities. Our data shed light on the importance of the auditory input in aggression and open perceptions to interpret how hearing and aggression interact at the molecular neural circuit level. url: https://doi.org/10.1101/2020.06.10.141325 doi: 10.1101/2020.06.10.141325 id: cord-323967-2mo915u1 author: Miersch, Shane title: Tetravalent SARS-CoV-2 Neutralizing Antibodies Show Enhanced Potency and Resistance to Escape Mutations date: 2020-11-01 words: 3231.0 sentences: 173.0 pages: flesch: 57.0 cache: ./cache/cord-323967-2mo915u1.txt txt: ./txt/cord-323967-2mo915u1.txt summary: Moreover, structural studies reveal that the best nAb targets the host receptor binding site of the virus spike protein, and thus, its tetravalent version can block virus infection with a potency that exceeds that of the bivalent IgG by an order of magnitude. Moreover, the use of a highly stable framework 77 enabled facile and modular design of ultra-high affinity nAbs in tetravalent formats that retained 78 favorable drug-like properties and exhibited neutralization potencies that greatly exceeded those 79 of the bivalent IgG format. Fab-phage were screened by ELISA and those that exhibited >50% loss in binding 92 to RBD in the presence of 200 nM ACE2 were sequenced, revealing 34 unique clones (Fig. 1A) , 93 deemed to be potential nAbs and converted into the full-length human IgG1 format for 94 purification and functional characterization. abstract: Recombinant neutralizing antibodies (nAbs) derived from recovered patients have proven to be effective therapeutics for COVID-19. Here, we describe the use of advanced protein engineering and modular design principles to develop tetravalent synthetic nAbs that mimic the multi-valency exhibited by IgA molecules, which are especially effective natural inhibitors of viral disease. At the same time, these nAbs display high affinity and modularity typical of IgG molecules, which are the preferred format for drugs. We show that highly specific tetravalent nAbs can be produced at large scale and possess stability and specificity comparable to approved antibody drugs. Moreover, structural studies reveal that the best nAb targets the host receptor binding site of the virus spike protein, and thus, its tetravalent version can block virus infection with a potency that exceeds that of the bivalent IgG by an order of magnitude. Design principles defined here can be readily applied to any antibody drug, including IgGs that are showing efficacy in clinical trials. Thus, our results present a general framework to develop potent antiviral therapies against COVID-19, and the strategy can be readily deployed in response to future pathogenic threats. url: https://doi.org/10.1101/2020.10.31.362848 doi: 10.1101/2020.10.31.362848 id: cord-330213-reb9vo7x author: Miladi, Milad title: The landscape of SARS-CoV-2 RNA modifications date: 2020-07-18 words: 3213.0 sentences: 210.0 pages: flesch: 55.0 cache: ./cache/cord-330213-reb9vo7x.txt txt: ./txt/cord-330213-reb9vo7x.txt summary: From sequencing three isolates, we derive a robust identification of SARS-CoV-2 modification sites within a physiologically relevant host cell type. A comparison of our data with the DRS data from a previous SARS-CoV-2 isolate, both raised in monkey renal cells, reveals consistent RNA modifications across the viral genome. The long RNA sequencing reads generated for this study cover the entire SARS-CoV-2 genomic RNA as well as the different ORFs (Fig 1b,c, Fig. S1b ). Two sets of Galaxy workflows based on Tombo (16) and Nanocompore (17) tools were designed to compute the modification scores from the DRS data (Table S3) . Figure 5 : Direct RNA sequencing raw electrical signals of downsampled reads obtained from unmodified RNA (IVT, black), from samples generated for this study and from isolate from a published korean data set (Fr1-3 and Kr, red). abstract: In 2019 the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the first documented cases of severe lung disease COVID-19. Since then, SARS-CoV-2 has been spreading around the globe resulting in a severe pandemic with over 500.000 fatalities and large economical and social disruptions in human societies. Gaining knowledge on how SARS-Cov-2 interacts with its host cells and causes COVID-19 is crucial for the intervention of novel therapeutic strategies. SARS-CoV-2, like other coronaviruses, is a positive-strand RNA virus. The viral RNA is modified by RNA-modifying enzymes provided by the host cell. Direct RNA sequencing (DRS) using nanopores enables unbiased sensing of canonical and modified RNA bases of the viral transcripts. In this work, we used DRS to precisely annotate the open reading frames and the landscape of SARS-CoV-2 RNA modifications. We provide the first DRS data of SARS-CoV-2 in infected human lung epithelial cells. From sequencing three isolates, we derive a robust identification of SARS-CoV-2 modification sites within a physiologically relevant host cell type. A comparison of our data with the DRS data from a previous SARS-CoV-2 isolate, both raised in monkey renal cells, reveals consistent RNA modifications across the viral genome. Conservation of the RNA modification pattern during progression of the current pandemic suggests that this pattern is likely essential for the life cycle of SARS-CoV-2 and represents a possible target for drug interventions. url: https://doi.org/10.1101/2020.07.18.204362 doi: 10.1101/2020.07.18.204362 id: cord-102458-7sssm3zk author: Milanez-Almeida, Pedro title: Blood gene expression-based prediction of lethality after respiratory infection by influenza A virus in mice date: 2020-10-27 words: 4637.0 sentences: 172.0 pages: flesch: 42.0 cache: ./cache/cord-102458-7sssm3zk.txt txt: ./txt/cord-102458-7sssm3zk.txt summary: During training (i.e., model selection via cross-validation), the algorithm learned that 11 genes had expression values in blood that could be linearly combined to generate a scoring system of infected animals as a function of the day of death ( In both the multinomial and the lethal Cox models, high levels of expression of genes associated with monocytes and neutrophils, together with low levels of transcripts associated with lymphocytes, indicated high risk of death (Fig. S3 ), consistent with previously described analyses of the immune response to IAV infection (10, 12, 13) and also recent data from COVID-19 patients (29). While the lack of accuracy later in the course of infection (i.e., days seven and eight) was likely due to the fact that the model was trained for early detection of lethality, before adaptive immune cells fully developed and reached the circulation, these data suggest that PAMPs and DAMPs eventually reach different levels in the lungs of different mice, impacting their blood cell composition and lethal score, which can be used for prediction of lethality of individual animals even in the challenging scenario of experimental infection with an 1 LD50 IAV dose. abstract: Lethality after respiratory infection with influenza A virus (IAV) is associated with potent immune activation and lung tissue damage. In a well-controlled animal model of infection, we sought to determine if one could predict lethality using transcriptional information obtained from whole blood early after influenza virus exposure. We started with publicly available transcriptomic data from the lung, which is the primary site of the infection and pathology, to derive a multigene transcriptional signature of death reflective of innate inflammation associated with tissue damage. We refined this affected tissue signature with data from infected mouse and human blood to develop and validate a machine learning model that can robustly predict survival in mice after IAV challenge using data obtained from as little as 10 μl of blood from early time points post infection. Furthermore, in genetically identical, cohoused mice infected with the same viral bolus, the same model can predict the lethality of individual animals but, intriguingly, only within a specific time window that overlapped with the early effector phase of adaptive immunity. These findings raise the possibility of predicting disease outcome in respiratory virus infections with blood transcriptional data and pave the way for translating such approaches to humans. url: https://doi.org/10.1101/2020.10.27.357053 doi: 10.1101/2020.10.27.357053 id: cord-103714-06hhlma3 author: Miller, Mariël title: Examination of a first-in-class bis-dialkylnorspermidine-terphenyl antibiotic in topical formulation against mono and polymicrobial biofilms date: 2020-06-04 words: 2440.0 sentences: 146.0 pages: flesch: 51.0 cache: ./cache/cord-103714-06hhlma3.txt txt: ./txt/cord-103714-06hhlma3.txt summary: In this study, an in vitro assessment was performed to determine the potential efficacy of a unique first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. Confocal imaging and staining indicated that CZ-01179 was 357 highly effective against well-established biofilms that were exposed to the formulated gel, 358 whereas clinical products had limited efficacy (Fig 5) . Outcomes indicated that of the clinical standards of care, gentamicin was most effective 366 against both monomicrobial and polymicrobial biofilms of MRSA and of P. CZ-01179 gels were more efficacious at 415 eradicating biofilms in all other cases when compared to the standard of care topicals in the 416 collagen tests (Fig. 6) . abstract: Biofilm-impaired tissue is a significant factor in chronic wounds such as diabetic foot ulcers. Most, if not all, anti-biotics in clinical use have been optimized against planktonic phenotypes. In this study, an in vitro assessment was performed to determine the potential efficacy of a unique first-in-class series of antibiofilm antibiotics and compare outcomes to current clinical standards of care. The agent, CZ-01179, was formulated into a hydrogel and tested against mature biofilms of a clinical isolate of methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa ATCC 27853 using two separate methods. In the first method, biofilms were grown on cellulose discs on an agar surface. Topical agents were spread on gauze and placed over the biofilms for 24 h. Biofilms were quantified and imaged with confocal and scanning electron microscopy. In the second method, biofilms were grown on bioabsorbable collagen coupons in a modified CDC biofilm reactor. Coupons were immersed in treatment for 24 h. The first method was limited in its ability to assess efficacy. Efficacy profiles against biofilms grown on collagen were more definitive, with CZ-01179 gel eradicating well-established biofilms to a greater degree compared to clinical standards. In conclusion, CZ-01179 may be a promising topical agent that targets the biofilm phenotype. Pre-clinical work is currently being performed to determine the translatable potential of CZ-01179 gel. url: https://doi.org/10.1101/2020.06.04.133934 doi: 10.1101/2020.06.04.133934 id: cord-274114-fglyfz8p author: Minervina, Anastasia A. title: Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection date: 2020-10-01 words: 5557.0 sentences: 297.0 pages: flesch: 56.0 cache: ./cache/cord-274114-fglyfz8p.txt txt: ./txt/cord-274114-fglyfz8p.txt summary: In this study we use longitudinal TCRalpha and TCRbeta repertoire sequencing to quantitatively track T cell clones that significantly expand and contract after recovery from a mild COVID-19 infection, and determine their phenotype. We reveal the dynamics and the phenotype of the memory cells formed after infection, identify pre-existing T cell memory clones participating in the response, and describe public TCR sequence motifs of SARS-CoV-2-reactive clones, suggesting a response to immunodominant epitopes. At the time of writing, no data on TCR sequences specific to MHC-II class epitopes exist to map specificities of CD4+ T-cells in a similar way as we did with MIRA-specific TCRs. However, a recently published database of 1414 bulk TCRbeta repertoires from COVID-19 patients allowed us to confirm the SARS-CoV-2 specificity of contracting clones indirectly. Public TCRbeta sequences that can recognize SARS-CoV-2 epitopes are expected to be clonally expanded and thus sampled more frequently in the repertoires of COVID-19 patients than in control donors. abstract: COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cells play a key role in the adaptive antiviral immune response by killing infected cells and facilitating the selection of virus-specific antibodies. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor (TCR) sequencing to track changes in the T cell repertoire following two mild cases of COVID-19. In both donors we identified CD4+ and CD8+ T cell clones with transient clonal expansion after infection. The antigen specificity of CD8+ TCR sequences to SARS-CoV-2 epitopes was confirmed by both MHC tetramer binding and presence in large database of SARS-CoV-2 epitope-specific TCRs. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones and show preferential occurence of these motifs in publicly available large dataset of repertoires from COVID-19 patients. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain T cell clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2. url: https://doi.org/10.1101/2020.05.18.100545 doi: 10.1101/2020.05.18.100545 id: cord-272869-381qupdn author: Mirvakili, Seyed M title: Reverse Pneumatic Artificial Muscles for Application in Low-Cost Artificial Respirators date: 2020-05-21 words: 6039.0 sentences: 361.0 pages: flesch: 58.0 cache: ./cache/cord-272869-381qupdn.txt txt: ./txt/cord-272869-381qupdn.txt summary: In this work, we propose a low-cost, portable, yet high-performance design for a volume-controlled mechanical ventilator. With the current design, mechanical ventilation for respiration rate ranging from 10 b/min to 30 b/min with a tidal volume range of 150 mL to 1000 mL and I:E ratio of 1:1 to 1:5 can be performed. The state-of-the-art mechanical ventilators address the need for all range of respiratory failures; however, their time-to-manufacture, design sophistication, cost, and scalability for deployment in mass emergencies such as pandemics, make them not a viable solution in many situations. The user interface lets the operator set parameters, stop/start the device, and monitor the pressure and flow rate on the LCD ( Figure 1C ). As depicted in Figure 7 , when pressure drops below -2 cmH2O, the device starts the ventilation and delivers the set tidal volume. abstract: One of the main challenges associated with mechanical ventilators is their limited availability in pandemics and other emergencies. Therefore, there is a great demand for mechanical ventilators to address this issue. In this work, we propose a low-cost, portable, yet high-performance design for a volume-controlled mechanical ventilator. We are employing pneumatic artificial muscles, such as air cylinders, in the reverse mode of operation to achieve mechanical ventilation. The current design of the device can operate in two modes: controlled mode and assisted mode. Unlike most ICU ventilators, our device does not need a high-pressure air pipeline to operate. With the current design, mechanical ventilation for respiration rate ranging from 10 b/min to 30 b/min with a tidal volume range of 150 mL to 1000 mL and I:E ratio of 1:1 to 1:5 can be performed. We achieved a total cost of less $400 USD to make one device. We estimate the device to cost less than $250 USD when produced in larger volumes. url: https://doi.org/10.1101/2020.05.20.107342 doi: 10.1101/2020.05.20.107342 id: cord-328659-miujzgtd author: Mishra, Akhilesh title: Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions date: 2020-07-27 words: 6064.0 sentences: 361.0 pages: flesch: 55.0 cache: ./cache/cord-328659-miujzgtd.txt txt: ./txt/cord-328659-miujzgtd.txt summary: title: Mutation landscape of SARS-CoV-2 reveals five mutually exclusive clusters of leading and trailing single nucleotide substitutions Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. The rapid global spread of SARS-CoV-2 in a short period of time and the availability of a large number of fully sequenced genomes provide us with a unique opportunity of understanding the short-term temporal evolution of this virus in humans in a near real-time scale. By this approach we propose the classification of the SARS-CoV-2 virus genomes into 5 mutually exclusive lineages with unique set of co-occurring mutations and geographic distribution. Our analysis revealed a total of 40 nucleotide substitutions which occurred at > 1% in the SARS-CoV-2 genomes (Table 1 and Figure 1A ). We consider a specific mutation or a set of cooccurring mutations as "lineage-defining" for SARS-CoV-2, only when they are present in at least 2% (n=30) of the sequences analysed. abstract: The COVID-19 pandemic has spread across the globe at an alarming rate. However, unlike any of the previous global outbreaks the availability of a large number of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 1448 full-length (>29000 nt) sequences available and identified 40 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, three of the 40 substitutions occur within highly conserved secondary structures in the 5’ and 3’ regions of the genomic RNA that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define five mutually exclusive lineages (A1, B1, C1, D1 and E1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2. Importance The SARS-CoV-2 / COVID-19 pandemic has spread far and wide with high infectivity. However, the severeness of the infection as well as the mortality rates differ greatly across different geographic areas. Here we report high frequency mutations in the SARS-CoV-2 genomes which show the presence of linage-defining, leading and trailing mutations. Moreover, we propose for the first time, five mutually exclusive clusters of SARS-CoV-2 which account for 75% of the genomes analysed. This will have implications in diagnosis, pathogenesis and vaccine design url: https://doi.org/10.1101/2020.05.07.082768 doi: 10.1101/2020.05.07.082768 id: cord-103408-vhrlrd2c author: Mishra, Preet title: Decision Support Systems based on Scientific Evidence: Bibliometric Networks of Invasive Lantana camara date: 2020-08-10 words: 3304.0 sentences: 143.0 pages: flesch: 46.0 cache: ./cache/cord-103408-vhrlrd2c.txt txt: ./txt/cord-103408-vhrlrd2c.txt summary: Network approach to decipher large data sets has long been known as one of the best analytical strategies, and this applies equally well for bibliographic information (Shiffrin and Börner, 2004) , with the added benefits of being able to explore, model and restructure literature metadata to draw insights from both static and dynamic representations of individuals, organizations or themes of research (Newman, 2004) . High dimensional literature metadata, when visualized efficiently through networks can reveal communities sharing common node or edge attributes in both coarse-grained and fine-grained routines (Babu et al., 2016) Availability of metadata can often overcome constraints of limited access to full-text and enable one to focus on a lower ease-of-access threshold, i.e. critical information within the title, abstract and citation. Here we present case studies from invasive plant species bibliographic metadata and share how emerging co-authorship networks can improve and inform decisions, and how diverse network visualizations can be integrated as modules in a DSS. abstract: Extraction and analysis of useful knowledge from the vast amount of relevant published literature can add valuable insights to any research theme or area of interest. We introduce a simplified bibliometric data analysis protocol for gaining substantial insights into research thematics, which can also serve as a handy practical skill for researchers, while working from home. In this paper, we provide ways of developing a holistic research strategy using bibliometric-data driven approaches that integrate network analysis and information management, without the need of full paper access. This protocol is a comprehensive multi-modular pathway for analysis of metadata obtained from major scientific publishing houses by use of a Decision Support System (DSS). A simple case study on the invasive species Lantana camara has been presented as a proof-of-concept to show how one can implement this DSS based protocol. Some perspectives are also provided on how the outcomes can be used directly or scaled up for long term research interventions. We hope that this work will simplify exploratory literature review, and enable rational design of research objectives for scholars, as well as development of comprehensive grant proposals that address gaps in research. url: https://doi.org/10.1101/2020.08.10.240879 doi: 10.1101/2020.08.10.240879 id: cord-103150-e9q8e62v author: Mishra, Shreya title: Improving gene-network inference with graph-wavelets and making insights about ageing associated regulatory changes in lungs date: 2020-11-04 words: 8216.0 sentences: 457.0 pages: flesch: 53.0 cache: ./cache/cord-103150-e9q8e62v.txt txt: ./txt/cord-103150-e9q8e62v.txt summary: Just like gene-expression profile, inferred gene network could also be used to find differences in two groups of cells(sample) [13] to reveal changes in the regulatory pattern caused due to disease, environmental exposure or ageing. In order to test the hypothesis that graph-based denoising could improve gene-network inference, we first evaluated the performance of our method on bulk expression data-set. Our approach of graph-wavelet based pre-processing of mESC scRNA-seq data-set improved the performance of gene-network inference methods by 8-10 percentage (Fig. 2B) . Similarly in comparison to graph-wavelet based denoising, the other 7 methods did not provided substantial improvement in AUC for overlap among gene-network inferred by two data-sets of mESC (Fig. 2C , supplementary Figure S1B ). However, graph wavelet-based filtering improved the overlap between networks inferred from different batches of scRNA-seq profile of mESC even if they were denoised separately (Fig. 2C , supplementary Figure S1B ). abstract: Using gene-regulatory-networks based approach for single-cell expression profiles can reveal un-precedented details about the effects of external and internal factors. However, noise and batch effect in sparse single-cell expression profiles can hamper correct estimation of dependencies among genes and regulatory changes. Here we devise a conceptually different method using graph-wavelet filters for improving gene-network (GWNet) based analysis of the transcriptome. Our approach improved the performance of several gene-network inference methods. Most Importantly, GWNet improved consistency in the prediction of generegulatory-network using single-cell transcriptome even in presence of batch effect. Consistency of predicted gene-network enabled reliable estimates of changes in the influence of genes not highlighted by differential-expression analysis. Applying GWNet on the single-cell transcriptome profile of lung cells, revealed biologically-relevant changes in the influence of pathways and master-regulators due to ageing. Surprisingly, the regulatory influence of ageing on pneumocytes type II cells showed noticeable similarity with patterns due to effect of novel coronavirus infection in Human Lung. url: https://doi.org/10.1101/2020.07.24.219196 doi: 10.1101/2020.07.24.219196 id: cord-103187-a255643n author: Mitchell, Evan title: Prophylactic host behaviour discourages pathogen exploitation date: 2019-12-19 words: 3196.0 sentences: 343.0 pages: flesch: 79.0 cache: ./cache/cord-103187-a255643n.txt txt: ./txt/cord-103187-a255643n.txt summary: Third, and most 253 important, numerical results indicate that the CSS exploitation rateξ changes in a simple 254 way as cost is reduced from its critical value to its natural lower limit at zero (figure 2). When the cost is above its critical value so that no one 298 is engaging in prophylaxis, then this mutant cannot invade a resident population at the CSS 299ξ = √ κ. If we then decrease the cost below its critical value so that individuals begin to 300 take prophylactic measures, the CSS exploitation level decreases away fromξ = √ κ and so 301 the mutant is still unable to invade the resident population. (( -epsil^2* xbar + 1)* ubar * bmax + k * cost )* kappa * xi^2 ... (( -epsil^2* xbar + 1)* ubar * bmax + k * cost )* kappa * xi^2 ... abstract: Much work has considered the evolution of pathogens, but little is known about how they respond to changes in host behaviour. We build a model where hosts are able to choose to engage in prophylactic measures that reduce the likelihood of disease transmission. This choice is mediated by costs and benefits associated with prophylaxis, but the fraction of hosts engaged in prophylaxis is also affected by population dynamics. We identify a critical cost threshold above which hosts do not engage in prophylaxis. Below the threshold, prophylactic host behaviour does occur and pathogen virulence, measured by the extent to which it exploits its host, is reduced by the action of selection relative to the level that would otherwise be predicted in the absence of prophylaxis. Our work emphasizes the significance of the dual nature of the trade-off faced by the pathogen between balancing transmission and recovery, and creating new infections in hosts engaging or not engaging in prophylaxis. url: https://doi.org/10.1101/2019.12.18.881383 doi: 10.1101/2019.12.18.881383 id: cord-267536-rvhwl4ea author: Miyashita, L title: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells date: 2020-05-27 words: 1093.0 sentences: 61.0 pages: flesch: 57.0 cache: ./cache/cord-267536-rvhwl4ea.txt txt: ./txt/cord-267536-rvhwl4ea.txt summary: title: Traffic-derived particulate matter and angiotensin-converting enzyme 2 expression in human airway epithelial cells Objective To assess the effect of traffic-derived PM10 on human airway epithelial cell ACE2 expression in vitro. Conclusion Traffic-related PM10 increases the expression of the receptor for SARS-CoV-2 in human respiratory epithelial cells. Culture of A549 cells with 5% CSE, a putative positive control, increased ACE2 expression (MFI, n=4, 0 (0 to 28) vs. We also found that traffic-derived PM 10 upregulates ACE2 expression in human primary nasal epithelial cells, suggesting that this response occurs throughout the respiratory tract. First, we did not determine whether increased In conclusion, this study provides the first mechanistic evidence that traffic-derived air pollution increases ACE2 expression in human airway cells and therefore 1 3 vulnerability to SARS-CoV-2 infection. abstract: Background The mechanism for the association between traffic-derived particulate matter less than 10 microns (PM10) and cases of COVID-19 disease reported in epidemiological studies is unknown. To infect cells, the spike protein of SARS-CoV-2 interacts with angiotensin-converting enzyme 2 (ACE2) on host airway cells. Increased ACE2 expression in lower airway cells in active smokers, suggests a potential mechanism whereby PM10 increases vulnerability to COVID-19 disease. Objective To assess the effect of traffic-derived PM10 on human airway epithelial cell ACE2 expression in vitro. Methods PM10 was collected from Marylebone Road (London) using a kerbside impactor. A549 and human primary nasal epithelial cells were cultured with PM10 for 2 h, and ACE2 expression (median fluorescent intensity; MFI) assessed by flow cytometry. We included cigarette smoke extract as a putative positive control. Data were analysed by either Mann-Whitney test, or Kruskal-Wallis with Dunn’s multiple comparisons test. Results PM10 at 10 μg/mL, and 20 μg/mL increased ACE2 expression in A549 cells (P<0.05, 0.01 vs. medium control, respectively). Experiments using a single PM10 concentration (10 μg/mL), found increased ACE2 expression in both A549 cells (control vs. PM10, median (IQR) MFI; 470 (0.1 to 1114) vs 6217 (5071 to 8506), P<0.01), and in human primary epithelial cells (0 (0 to 591) vs. 4000 (2610 to 7853), P<0.05). Culture of A549 cells with 5% cigarette smoke extract increased ACE2 expression (n=4, 0 (0 to 28) vs. 9088 (7557 to 15831, P<0.05). Conclusion Traffic-related PM10 increases the expression of the receptor for SARS-CoV-2 in human respiratory epithelial cells. url: https://doi.org/10.1101/2020.05.15.097501 doi: 10.1101/2020.05.15.097501 id: cord-296007-1gsgd22t author: Mohseni, Amir Hossein title: Inferring MHC interacting SARS-CoV-2 epitopes recognized by TCRs towards designing T cell-based vaccines date: 2020-09-12 words: 2327.0 sentences: 110.0 pages: flesch: 64.0 cache: ./cache/cord-296007-1gsgd22t.txt txt: ./txt/cord-296007-1gsgd22t.txt summary: Our TCR-pMHC models predicted that position 2 of the homologous peptide antigens ( Figure 1A ) related 2 2 0 to TCR-pMHC complex of SARS-CoV-2 as well as SARS-CoV and bat-CoV N proteins prefers the 2 2 1 hydrophobic amino acid residues (e.g. Ile, Leu, Met, and Phe), and the second position of these hit peptides 2 2 2 is an hydrophobic amino acid residue Pro forming five strong VDW forces with residues Y99, V67, M45, 2 2 3 Y7, and F9 and two H-bonds with residues K66 and E63 on MHC molecule ( Figure S2A , left). Visualization of interactions in the atomic level structure of a TCR-pMHC complex in the hit peptide of 2 4 9 SARS-CoV-2 N protein for HLA-E ( Figure S3C ) within 20 and 8 Å was generated on-the-fly using of the homologous peptide antigens of all queries has no detectable binding to both MHC and TCR. abstract: The coronavirus disease 2019 (COVID-19) is triggered by severe acute respiratory syndrome mediated by coronavirus 2 (SARS-CoV-2) infection and was declared by WHO as a major international public health concern. While worldwide efforts are being advanced towards vaccine development, the structural modeling of TCR-pMHC (T Cell Receptor-peptide-bound Major Histocompatibility Complex) regarding SARS-CoV-2 epitopes and the design of effective T cell vaccine based on these antigens are still unresolved. Here, we present both pMHC and TCR-pMHC interfaces to infer peptide epitopes of the SARS-CoV-2 proteins. Accordingly, significant TCR-pMHC templates (Z-value cutoff > 4) along with interatomic interactions within the SARS-CoV-2-derived hit peptides were clarified. Also, we applied the structural analysis of the hit peptides from different coronaviruses to highlight a feature of evolution in SARS-CoV-2, SARS-CoV, bat-CoV, and MERS-CoV. Peptide-protein flexible docking between each of the hit peptides and their corresponding MHC molecules were performed, and a multi-hit peptides vaccine against the S and N glycoprotein of SARS-CoV-2 was designed. Filtering pipelines including antigenicity, and also physiochemical properties of designed vaccine were then evaluated by different immunoinformatics tools. Finally, vaccine-structure modeling and immune simulation of the desired vaccine were performed aiming to create robust T cell immune responses. We anticipate that our design based on the T cell antigen epitopes and the frame of the immunoinformatics analysis could serve as valuable supports for the development of COVID-19 vaccine. url: https://doi.org/10.1101/2020.09.12.294413 doi: 10.1101/2020.09.12.294413 id: cord-284068-sbon3aes author: Mok, Chee Keng title: Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis date: 2020-06-22 words: 1798.0 sentences: 104.0 pages: flesch: 49.0 cache: ./cache/cord-284068-sbon3aes.txt txt: ./txt/cord-284068-sbon3aes.txt summary: Validation assays to determine changes in infectious virus titres upon treatment was carried out by testing selected hit compounds in dose-dependent assays in Vero E6 to confirm the primary screen observation and also in the human hepatocarcinoma HuH7 cell line as the latter cell line expresses high levels of the ACE2 receptor (10) and supports replication of coronaviruses (11) . While recent data has shown that vitamin D levels are negatively associated with morbidity and mortality of COVID-19 cases (13, 14) , this is the first report of a direct inhibitory effect of calcitriol on SARS-CoV-2. The authors speculated that vitamin D supplementation could protect against SARS-CoV-2 infection and improve patient disease outcomes (16) , and our finding certainly provides credence to this hypothesis. Given the high transmissibility of SARS-CoV-2 globally (23), if these findings can be replicated in clinical trials, calcitriol may certainly prove to be an effective tool in the effort to control the pandemic while waiting for an effective vaccine to be rolled out globally. abstract: COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients. url: https://doi.org/10.1101/2020.06.21.162396 doi: 10.1101/2020.06.21.162396 id: cord-340516-9dfaqsv7 author: Moore, Anne C. title: Pre-clinical studies of a recombinant adenoviral mucosal vaccine to prevent SARS-CoV-2 infection date: 2020-09-06 words: 6679.0 sentences: 335.0 pages: flesch: 48.0 cache: ./cache/cord-340516-9dfaqsv7.txt txt: ./txt/cord-340516-9dfaqsv7.txt summary: We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Here, we report the induction of neutralizing antibody (Nab), IgG and IgA antibody responses, and T cell responses in mice following immunization of rAd vectors expressing one or more SARS-CoV-2 antigens. We have previously demonstrated that an oral, tableted rAd-based vaccine can induce protection against respiratory infection and shedding following influenza virus challenge 15 as well as intestinal immunity to norovirus antigens in humans 12 . In summary, these studies in mice represent our first step in creating a vaccine candidate, demonstrating the immunogenicity of the construct at even low vaccine doses and the elucidation of the full-length spike protein as a leading candidate antigen to induce T cell responses and superior systemic and mucosal neutralizing antibody. abstract: There is an urgent need to develop efficacious vaccines against SARS-CoV-2 that also address the issues of deployment, equitable access, and vaccine acceptance. Ideally, the vaccine would prevent virus infection and transmission as well as preventing COVID-19 disease. We previously developed an oral adenovirus-based vaccine technology that induces both mucosal and systemic immunity in humans. Here we investigate the immunogenicity of a range of candidate adenovirusbased vaccines, expressing full or partial sequences of the spike and nucleocapsid proteins, in mice. We demonstrate that, compared to expression of the S1 domain or a stabilized spike antigen, the full length, wild-type spike antigen induces significantly higher neutralizing antibodies in the periphery and in the lungs, when the vaccine is administered mucosally. Antigen-specific CD4+ and CD8+ T cells were induced by this leading vaccine candidate at low and high doses. This fulllength spike antigen plus nucleocapsid adenovirus construct has been prioritized for further clinical development. url: https://doi.org/10.1101/2020.09.04.283853 doi: 10.1101/2020.09.04.283853 id: cord-104030-eb29t38n author: Morales-Nebreda, Luisa title: Aging imparts cell-autonomous dysfunction to regulatory T cells during recovery from influenza pneumonia date: 2020-06-05 words: 3960.0 sentences: 175.0 pages: flesch: 36.0 cache: ./cache/cord-104030-eb29t38n.txt txt: ./txt/cord-104030-eb29t38n.txt summary: Using heterochronic (age-mismatched) adoptive Treg cell transfer experiments and molecular profiling in mice, we sought to determine whether the age-related impairment in repair following influenza-induced lung injury is intrinsic to Treg cells. Our data support a paradigm in which aged Treg cells fail to upregulate youthful reparative programs, activate maladaptive responses and consequently exhibit a cell-autonomous impairment in pro-recovery function, which delays resolution from viralinduced lung injury in aged hosts. Gene set enrichment analysis of these genes demonstrated that this methylation-regulated gene expression program was associated with pro-recovery processes and was significantly skewed toward young Treg cells ( Figure 6C) . Combined, these results show that age-related DNA methylation regulates the pro-reparative transcriptional regulatory network during recovery from influenza-induced lung injury. What are the molecular mechanisms underpinning the age-associated Treg cell gain or loss-of pro-reparative function in the lung following influenza infection? abstract: Regulatory T (Treg) cells orchestrate resolution and repair of acute lung inflammation and injury following viral pneumonia. Compared with younger patients, older individuals experience impaired recovery and worse clinical outcomes after severe viral infections, including influenza and the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Whether age is a key determinant of Treg cell pro-repair function following lung injury remains unknown. Here, we show that aging results in a cell-autonomous impairment of reparative Treg cell function following experimental influenza pneumonia. Transcriptional and DNA methylation profiling of sorted Treg cells provide insight into the mechanisms underlying their age-related dysfunction, with Treg cells from aged mice demonstrating both loss of reparative programs and gain of maladaptive programs. Novel strategies that restore youthful Treg cell functional programs could be leveraged as therapies to improve outcomes among older individuals with severe viral pneumonia. url: https://doi.org/10.1101/2020.06.05.135194 doi: 10.1101/2020.06.05.135194 id: cord-104128-0gyk9cwx author: Morand, Serge title: The accelerated infectious disease risk in the Anthropocene: more outbreaks and wider global spread date: 2020-04-20 words: 7037.0 sentences: 358.0 pages: flesch: 47.0 cache: ./cache/cord-104128-0gyk9cwx.txt txt: ./txt/cord-104128-0gyk9cwx.txt summary: Countries which are more centrally located within these disease networks tend to be also the more developed and emerging countries with significantly higher GDPs. Therefore, one cost of increased global mobility (which is currently tightly linked to economic growth and globalization, see Discussion below) is the increased risk of disease outbreaks and their faster and wider spread (although we note that the risk per capita may be decreasing, Smith et al., 2014) . Similarly, increasing levels of (1) isolation of infectious hosts, household quarantine and related behavioral changes which reduce transmission rates and (2) air traffic reduction increasingly slowed the global spread of influenza, although the latter control strategy required the almost complete halt of global air traffic (Cooper et al., 2006; Ferguson et al., 2006; Flahault et al., 2006; Hollingsworth et al., 2006; Epstein et al., 2007; Bajardi 11 et al., 2011) . abstract: The greatly accelerated economic growth during the Anthropocene has resulted in astonishing improvements in many aspects of human well-being, but has also caused the acceleration of risks, such as the interlinked biodiversity and climate crisis. Here, we report on another risk: the accelerated infectious disease risk associated with the number and geographic spread of human infectious disease outbreaks. Using the most complete, reliable, and up-to-date database on human infectious disease outbreaks (GIDEON), we show that the number of disease outbreaks, the number of diseases involved in these outbreaks, and the number of countries affected have increased during the entire Anthropocene. Furthermore, the spatial distribution of these outbreaks is becoming more globalized in the sense that the overall modularity of the disease networks across the globe has decreased, meaning disease outbreaks have become increasingly pandemic in their nature. This decrease in modularity is correlated with the increase in air traffic. We finally show that those countries and regions which are most central within these disease networks tend to be countries with higher GDPs. Therefore, one cost of increased global mobility and greater economic growth is the increased risk of disease outbreaks and their faster and wider spread. We briefly discuss three different scenarios which decision-makers might follow in light of our results. url: https://doi.org/10.1101/2020.04.20.049866 doi: 10.1101/2020.04.20.049866 id: cord-311240-o0zyt2vb author: Motayo, Babatunde Olarenwaju title: Evolution and Genetic Diversity of SARSCoV-2 in Africa Using Whole Genome Sequences date: 2020-07-27 words: 3091.0 sentences: 167.0 pages: flesch: 50.0 cache: ./cache/cord-311240-o0zyt2vb.txt txt: ./txt/cord-311240-o0zyt2vb.txt summary: Our study has revealed a rapidly diversifying viral population with the G614 spike protein variant dominating, we advocate for up scaling NGS sequencing platforms across Africa to enhance surveillance and aid control effort of SARSCoV-2 in Africa. The pathogen was later identified to be a novel coronavirus closely related to the severe acute respiratory syndrome virus (SARS), with a possible bat origin (Zhou et al, 2020) . This study was designed to determine to the genetic diversity and evolutionary history of genome sequences of SARSCoV-2 isolated in Africa. Results of recombination analysis of the African SARSCoV-2 (AfrSARSCoV-2) sequences against references whole genome sequences of SARS, Recombination signals were observed between the African SARSCoV-2 sequences and reference sequence (Major recombinant hCoV-19 Pangolin/Guangu P4L/2017; Minor parent hCoV-19 B batYunan/RaTG13) between the RdRP and S gene regions (Figure 2 ). abstract: The ongoing SARSCoV-2 pandemic was introduced into Africa on 14th February 2020 and has rapidly spread across the continent causing severe public health crisis and mortality. We investigated the genetic diversity and evolution of this virus during the early outbreak months using whole genome sequences. We performed; recombination analysis against closely related CoV, Bayesian time scaled phylogeny and investigated spike protein amino acid mutations. Results from our analysis showed recombination signals between the AfrSARSCoV-2 sequences and reference sequences within the N and S genes. The evolutionary rate of the AfrSARSCoV-2 was 4.133 × 10−4 high posterior density HPD (4.132 × 10−4 to 4.134 × 10−4) substitutions/site/year. The time to most recent common ancestor TMRCA of the African strains was December 7th 2019. The AfrSARCoV-2 sequences diversified into two lineages A and B with B being more diverse with multiple sub-lineages confirmed by both maximum clade credibility MCC tree and PANGOLIN software. There was a high prevalence of the D614-G spike protein amino acid mutation (82.61%) among the African strains. Our study has revealed a rapidly diversifying viral population with the G614 spike protein variant dominating, we advocate for up scaling NGS sequencing platforms across Africa to enhance surveillance and aid control effort of SARSCoV-2 in Africa. url: https://doi.org/10.1101/2020.07.27.222901 doi: 10.1101/2020.07.27.222901 id: cord-312524-ee5xw1r8 author: Moustafa, Ahmed M. title: Rapid whole genome sequence typing reveals multiple waves of SARS-CoV-2 spread date: 2020-06-08 words: 2058.0 sentences: 129.0 pages: flesch: 61.0 cache: ./cache/cord-312524-ee5xw1r8.txt txt: ./txt/cord-312524-ee5xw1r8.txt summary: Here we present a rapid, whole genome, allele-based method (GNUVID) for assigning sequence types to sequenced isolates of SARS-CoV-2 sequences. Rapid sequencing of the SARS-CoV-2 pandemic virus has presented an 40 unprecedented opportunity to track the evolution of the virus and to understand the 41 emergence of a new pathogen in near-real time. Our panallelome approach to developing a whole genome (wgMLST) scheme for 58 SARS-CoV-2 uses a modified version of our recently developed tool, WhatsGNU [10], 59 to rapidly assign an allele number to each gene nucleotide sequence in the virus''s 60 genome creating a sequence type (ST). We developed the GNU-based Virus IDentification (GNUVID) system as a tool 71 that automatically assigns a number to each unique allele of the 10 open reading 72 frames (ORFs) of SARS-CoV-2 ( Figure 1A) information. When the global region of origin for each genome sequence was mapped to 102 each CC there was a strong association of some CCs with certain geographical 103 locations. abstract: As the pandemic SARS-CoV-2 virus has spread globally its genome has diversified to an extent that distinct clones can now be recognized, tracked, and traced. Identifying clonal groups allows for assessment of geographic spread, transmission events, and identification of new or emerging strains that may be more virulent or more transmissible. Here we present a rapid, whole genome, allele-based method (GNUVID) for assigning sequence types to sequenced isolates of SARS-CoV-2 sequences. This sequence typing scheme can be updated with new genomic information extremely rapidly, making our technique continually adaptable as databases grow. We show that our method is consistent with phylogeny and recovers waves of expansion and replacement of sequence types/clonal complexes in different geographical locations. GNUVID is available as a command line application (https://github.com/ahmedmagds/GNUVID). url: https://doi.org/10.1101/2020.06.08.139055 doi: 10.1101/2020.06.08.139055 id: cord-280454-etf32afd author: Moustaqil, Mehdi title: SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts date: 2020-06-05 words: 10152.0 sentences: 562.0 pages: flesch: 56.0 cache: ./cache/cord-280454-etf32afd.txt txt: ./txt/cord-280454-etf32afd.txt summary: title: SARS-CoV-2 proteases cleave IRF3 and critical modulators of inflammatory pathways (NLRP12 and TAB1): implications for disease presentation across species and the search for reservoir hosts Direct cleavage of IRF3 by NSP3 could explain the blunted TypeI IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of IL-6 and inflammatory response observed in COVID-19 patients. In this report, we show that the viral proteases PLpro and 3CLpro of SARS-CoV2 lead to the in-vitro proteolytic cleavage of three important proteins of the host immune response: IRF3, TAB1 and NLRP12 (Fig. 1B) . The presence of the five human-like cleavage sites for IRF3, TAB1 and NLRP12 in a single species shows that it is possible that the SARS viruses could have gained the new functionality of cleaving these Human Innate Immune Proteins in a single reservoir host, potentially in Myotis Davidii. abstract: The genome of SARS-CoV-2 (SARS2) encodes for two viral proteases (NSP3/ papain-like protease and NSP5/ 3C-like protease or major protease) that are responsible for cleaving viral polyproteins for successful replication. NSP3 and NSP5 of SARS-CoV (SARS1) are known interferon antagonists. Here, we examined whether the protease function of SARS2 NSP3 and NSP5 target proteins involved in the host innate immune response. We designed a fluorescent based cleavage assay to rapidly screen the protease activity of NSP3 and NSP5 on a library of 71 human innate immune proteins (HIIPs), covering most pathways involved in human innate immunity. By expressing each of these HIIPs with a genetically encoded fluorophore in a cell-free system and titrating in the recombinant protease domain of NSP3 or NSP5, we could readily detect cleavage of cognate HIIPs on SDS-page gels. We identified 3 proteins that were specifically and selectively cleaved by NSP3 or NSP5: IRF-3, and NLRP12 and TAB1, respectively. Direct cleavage of IRF3 by NSP3 could explain the blunted Type- I IFN response seen during SARS-CoV-2 infections while NSP5 mediated cleavage of NLRP12 and TAB1 point to a molecular mechanism for enhanced production of IL-6 and inflammatory response observed in COVID-19 patients. Surprisingly, both NLRP12 and TAB1 have each two distinct cleavage sites. We demonstrate that in mice, the second cleavage site of NLRP12 is absent. We pushed this comparative alignment of IRF-3 and NLRP12 homologs and show that the lack or presence of cognate cleavage motifs in IRF-3 and NLRP12 could contribute to the presentation of disease in cats and tigers, for example. Our findings provide an explanatory framework for in-depth studies into the pathophysiology of COVID-19 and should facilitate the search or development of more effective animal models for severe COVID-19. Finally, we discovered that one particular species of bats, David’s Myotis, possesses the five cleavage sites found in humans for NLRP12, TAB1 and IRF3. These bats are endemic from the Hubei province in China and we discuss its potential role as reservoir for the evolution of SARS1 and SASR2. url: https://doi.org/10.1101/2020.06.05.135699 doi: 10.1101/2020.06.05.135699 id: cord-296187-nnv2e7gr author: Mulgaonkar, Nirmitee title: Bcr-Abl tyrosine kinase inhibitor imatinib as a potential drug for COVID-19 date: 2020-08-18 words: 4943.0 sentences: 306.0 pages: flesch: 57.0 cache: ./cache/cord-296187-nnv2e7gr.txt txt: ./txt/cord-296187-nnv2e7gr.txt summary: The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered as a potential target for drug development. Based on in silico screening followed by in vitro studies, here we report that the existing FDA-approved Bcr-Abl tyrosine kinase inhibitor, imatinib, inhibits SARS-CoV-2 with an IC50 of 130 nM. We provide evidence that although imatinib binds to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein with an affinity at micromolar, i.e., 2.32 ± 0.9 μM levels, imatinib does not directly inhibit the spike RBD:ACE2 interaction – suggesting a Bcr-Abl kinase-mediated fusion inhibition mechanism is responsible for the inhibitory action. This study utilizes in silico methodology followed by in vitro experimental validation to screen existing FDA-approved small molecule drugs specific to the RBD of the spike protein of SARS-CoV-2 to identify repurposable drugs targeting further clinical validation. abstract: The rapid geographic expansion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the infectious agent of Coronavirus Disease 2019 (COVID-19) pandemic, poses an immediate need for potent drugs. Enveloped viruses infect the host cell by cellular membrane fusion, a crucial mechanism required for virus replication. The SARS-CoV-2 spike glycoprotein, due to its primary interaction with the human angiotensin-converting enzyme 2 (ACE2) cell-surface receptor, is considered as a potential target for drug development. Based on in silico screening followed by in vitro studies, here we report that the existing FDA-approved Bcr-Abl tyrosine kinase inhibitor, imatinib, inhibits SARS-CoV-2 with an IC50 of 130 nM. We provide evidence that although imatinib binds to the receptor-binding domain (RBD) of SARS-CoV-2 spike protein with an affinity at micromolar, i.e., 2.32 ± 0.9 μM levels, imatinib does not directly inhibit the spike RBD:ACE2 interaction – suggesting a Bcr-Abl kinase-mediated fusion inhibition mechanism is responsible for the inhibitory action. We also show that imatinib inhibits other coronaviruses, SARS-CoV, and MERS-CoV via fusion inhibition. Based on promising in vitro results, we propose the Abl tyrosine kinase inhibitor (ATKI), imatinib, to be a viable repurposable drug against COVID-19. url: https://doi.org/10.1101/2020.06.18.158196 doi: 10.1101/2020.06.18.158196 id: cord-103597-mt0h06y3 author: Muller, Alana title: Neurophysiological Correlates of the Dunning-Kruger Effect date: 2020-05-20 words: 14179.0 sentences: 640.0 pages: flesch: 45.0 cache: ./cache/cord-103597-mt0h06y3.txt txt: ./txt/cord-103597-mt0h06y3.txt summary: Between-group EEG differences were evident between over-estimators and under-estimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators from 400-600 ms, whereas ''old-new'' memory ERP effects revealed a late parietal component (LPC) associated with recollection-based processing from 600-900 ms for under-estimators that was not evident for over-estimators. Results Between-group EEG differences were evident between over-estimators and underestimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators from 400-600 ms, whereas ''oldnew'' memory ERP effects revealed a late parietal component (LPC) associated with recollection-based processing from 600-900 ms for under-estimators that was not evident for over-estimators. One suggestion from these results is that the frontal effect at 400-600 ms may be characteristic of the FN400 ERP effect related to familiarity-based processing, in that over-estimators may be relying on the less-specific memory process of familiarity or intuitions of increased fluency to guide making their metacognitive judgments, instead of relying upon the more distinct recollection-related processes (Yonelinas et al., 2010 ) that evidently appears to be supporting the people who were under-estimating their performance relative to the group (Figure 7 ). abstract: The Dunning-Kruger Effect (DKE) is a metacognitive phenomenon of illusory superiority in which individuals who perform poorly on a task believe they performed better than others, yet individuals who performed very well believe they under-performed compared to others. This phenomenon has yet to be directly explored in episodic memory, nor explored for reaction times or physiological correlates. We designed a novel method to elicit the DKE via a test of item recognition while electroencephalography (EEG) was recorded. Throughout the task, participants were asked to estimate the percentile in which they performed compared to others. Results revealed participants in the bottom 25th percentile overestimated their percentile, while participants in the top 75th percentile underestimated their percentile, exhibiting the classic DKE. Reaction time measures revealed a condition x group interaction whereby over-estimators responded faster than under-estimators when estimating being in the top percentile and responded slower when estimating being in the bottom percentile. Between-group EEG differences were evident between over-estimators and under-estimators during Dunning-Kruger responses, which revealed FN400-like effects of familiarity supporting differences for over-estimators from 400-600 ms, whereas ‘old-new’ memory ERP effects revealed a late parietal component (LPC) associated with recollection-based processing from 600-900 ms for under-estimators that was not evident for over-estimators. Findings suggest over- and under-estimators use differing cognitive processes when assessing their performance, such that under-estimators rely on recollection during memory and over-estimators draw upon excess familiarity when over-estimating their performance. Episodic memory thus appears to play a contributory role in metacognitive judgments of illusory superiority and inferiority. Graphical Abstract Event-related potentials (ERPS) were recorded for the Dunning-Kruger Effect as subjects made metacognitive judgments about performance on a memory task. Over- and Under-estimators exhibited a crossover interaction in response times when believing they did best and worst, respectively. A crossover pattern was also observed for ERPs: LPC signals of recollection were found for under-estimators, whereas familiarity-based FN400 effects were evident for over-estimators and correlated with estimates. url: https://doi.org/10.1101/2019.12.26.888511 doi: 10.1101/2019.12.26.888511 id: cord-262602-on0w55x0 author: Muruato, Antonio E. title: A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation date: 2020-05-22 words: 880.0 sentences: 53.0 pages: flesch: 53.0 cache: ./cache/cord-262602-on0w55x0.txt txt: ./txt/cord-262602-on0w55x0.txt summary: Therefore, a high-throughput assay to measure SARS-CoV-2 neutralizing antibodies is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, and vaccine development. Here we report on a fluorescence-based SARS-CoV-2 neutralization assay that detects SARS-CoV-2 neutralizing antibodies in COVID-19 patient specimens and yields comparable results to plaque reduction neutralizing assay, the gold standard of serological testing. To validate the reporter virus neutralization results, we performed the conventional 6 4 PRNT on the same set of patient specimens. The results demonstrate that when diagnosing 6 8 patient specimens, the reporter virus assay delivers neutralization results comparable to the 6 9 PRNT assay, the gold standard of serological testing. Next, we evaluated the specificity of reporter neutralization assay using potentially cross-7 1 reactive sera and interfering substances (Table 1) . Nevertheless, the 1 0 3 mNeonGreen reporter assay offers a rapid, high-throughput platform to test COVID-19 patient 1 0 4 sera not previously available. abstract: Virus neutralization remains the gold standard for determining antibody efficacy. Therefore, a high-throughput assay to measure SARS-CoV-2 neutralizing antibodies is urgently needed for COVID-19 serodiagnosis, convalescent plasma therapy, and vaccine development. Here we report on a fluorescence-based SARS-CoV-2 neutralization assay that detects SARS-CoV-2 neutralizing antibodies in COVID-19 patient specimens and yields comparable results to plaque reduction neutralizing assay, the gold standard of serological testing. Our approach offers a rapid platform that can be scaled to screen people for antibody protection from COVID-19, a key parameter necessary to safely reopen local communities. url: https://doi.org/10.1101/2020.05.21.109546 doi: 10.1101/2020.05.21.109546 id: cord-262470-nkql7h9x author: Muus, Christoph title: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells date: 2020-04-20 words: 17577.0 sentences: 869.0 pages: flesch: 50.0 cache: ./cache/cord-262470-nkql7h9x.txt txt: ./txt/cord-262470-nkql7h9x.txt summary: title: Integrated analyses of single-cell atlases reveal age, gender, and smoking status associations with cell type-specific expression of mediators of SARS-CoV-2 viral entry and highlights inflammatory programs in putative target cells Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. To assess the association of age, sex, and smoking status with the expression of ACE2, TMPRSS2, and CTSL, we aggregated 22 scRNA-seq datasets of healthy human nasal and lung cells, as well as fetal samples. abstract: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, creates an urgent need for identifying molecular mechanisms that mediate viral entry, propagation, and tissue pathology. Cell membrane bound angiotensin-converting enzyme 2 (ACE2) and associated proteases, transmembrane protease serine 2 (TMPRSS2) and Cathepsin L (CTSL), were previously identified as mediators of SARS-CoV2 cellular entry. Here, we assess the cell type-specific RNA expression of ACE2, TMPRSS2, and CTSL through an integrated analysis of 107 single-cell and single-nucleus RNA-Seq studies, including 22 lung and airways datasets (16 unpublished), and 85 datasets from other diverse organs. Joint expression of ACE2 and the accessory proteases identifies specific subsets of respiratory epithelial cells as putative targets of viral infection in the nasal passages, airways, and alveoli. Cells that co-express ACE2 and proteases are also identified in cells from other organs, some of which have been associated with COVID-19 transmission or pathology, including gut enterocytes, corneal epithelial cells, cardiomyocytes, heart pericytes, olfactory sustentacular cells, and renal epithelial cells. Performing the first meta-analyses of scRNA-seq studies, we analyzed 1,176,683 cells from 282 nasal, airway, and lung parenchyma samples from 164 donors spanning fetal, childhood, adult, and elderly age groups, associate increased levels of ACE2, TMPRSS2, and CTSL in specific cell types with increasing age, male gender, and smoking, all of which are epidemiologically linked to COVID-19 susceptibility and outcomes. Notably, there was a particularly low expression of ACE2 in the few young pediatric samples in the analysis. Further analysis reveals a gene expression program shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues, including genes that may mediate viral entry, subtend key immune functions, and mediate epithelial-macrophage cross-talk. Amongst these are IL6, its receptor and co-receptor, IL1R, TNF response pathways, and complement genes. Cell type specificity in the lung and airways and smoking effects were conserved in mice. Our analyses suggest that differences in the cell type-specific expression of mediators of SARS-CoV-2 viral entry may be responsible for aspects of COVID-19 epidemiology and clinical course, and point to putative molecular pathways involved in disease susceptibility and pathogenesis. url: https://doi.org/10.1101/2020.04.19.049254 doi: 10.1101/2020.04.19.049254 id: cord-292862-ezrkg0dc author: Myerson, Jacob W. title: Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment date: 2020-04-18 words: 14275.0 sentences: 744.0 pages: flesch: 46.0 cache: ./cache/cord-292862-ezrkg0dc.txt txt: ./txt/cord-292862-ezrkg0dc.txt summary: We show that polystyrene nanoparticles and five liposome formulations do not accumulate in injured lungs, indicating that nanostructures that are not based on protein are not intrinsically drawn to marginated neutrophils in acute inflammation. 6, 10, 14, 18 Single cell suspensions prepared from mouse lungs were probed by flow cytometry to further characterize pulmonary neutrophils in naïve mice and in mice following LPS-induced inflammation. The protein component of each particle was labeled with 125 I for tracing in biodistributions, and assessed 30 minutes after IV administration of NPs. Both absolute LDNG lung uptake and ratio of lung uptake to liver uptake registered a ~25-fold increase between naïve control and LPS-injured animals (Figure 2A , Supplementary Table 1) . As with LDNGs and albumin NPs in Figure 2C -H, single cell suspensions were prepared from LPS-inflamed and naïve control lungs after circulation of fluorescent DBCO-IgG liposomes. abstract: Acute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries (“margination”). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemic ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections. url: https://doi.org/10.1101/2020.04.15.037564 doi: 10.1101/2020.04.15.037564 id: cord-349364-vert186n author: Márquez-López, Cristina title: SARS-CoV-2 protein Nsp1 alters actomyosin cytoskeleton and phenocopies arrhythmogenic cardiomyopathy-related PKP2 mutant date: 2020-09-14 words: 5246.0 sentences: 286.0 pages: flesch: 48.0 cache: ./cache/cord-349364-vert186n.txt txt: ./txt/cord-349364-vert186n.txt summary: The fact that Nsp1 and PKP2 mutant R735X share similar phenotypes also suggests that direct SARS-CoV-2 heart infection could induce a transient ACM-like disease in COVID-19 patients, which may contribute to right ventricle dysfunction, observed in patients with poor survival prognosis. Using atomic force microscopy together with fluorescence imaging, we show that expression of PKP2 (c.2203C>T), encoding the R735X mutant found in ACM patients from different families (Alcalde et al., 2014; Gerull et al, 2004) alters cell mechanical stiffness, and alike Nsp1, modifies actomyosin cytoskeleton. All together, these results suggest that cytoplasmic localization of PKP2 either by a mutant involved in ACM development, or by Nsp1 hijack by SARS-CoV-2 infection can alter the integrity and assembly of the actin cytoskeleton by modulating the cortical distribution of Myh9 and Myh10. abstract: Mutations in desmosomal Plakophilin-2 (PKP2) are the most prevalent drivers of arrhythmogenic cardiomyopathy (ACM) and a common cause of sudden cardiac death in young athletes. However, partner proteins that elucidate PKP2 cellular mechanism to understand cardiac dysfunction in ACM are mostly unknown. Here we identify the actin-based motor proteins Myh9 and Myh10 as key PKP2 interactors, and demonstrate that the expression of the ACM-related PKP2 mutant R735X alters actin fiber organization and cell mechanical stiffness. We also show that SARS-CoV-2 Nsp1 protein acts similarly to this known pathogenic R735X mutant, altering the actomyosin component distribution on cardiac cells. Our data reveal that the viral Nsp1 hijacks PKP2 into the cytoplasm and mimics the effect of delocalized R735X mutant. These results demonstrate that cytoplasmic PKP2, wildtype or mutant, induces the collapse of the actomyosin network, since shRNA-PKP2 knockdown maintains the cell structure, validating a critical role of PKP2 localization in the regulation of actomyosin architecture. The fact that Nsp1 and PKP2 mutant R735X share similar phenotypes also suggests that direct SARS-CoV-2 heart infection could induce a transient ACM-like disease in COVID-19 patients, which may contribute to right ventricle dysfunction, observed in patients with poor survival prognosis. Highlights The specific cardiac isoform Plakophilin-2a (PKP2) interacts with Myh9 and Myh10. PKP2 delocalization alters actomyosin cytoskeleton component organization. SARS-CoV-2 Nsp1 protein hijacks PKP2 from the desmosome into the soluble fraction where it is downregulated. Viral Nsp1 collapses the actomyosin cytoskeleton and phenocopies the arrhythmogenic cardiomyopathy-related mutant R735X. url: https://doi.org/10.1101/2020.09.14.296178 doi: 10.1101/2020.09.14.296178 id: cord-103892-v6gkubd4 author: Mäkinen, Janne J. title: The mechanism of the nucleo-sugar selection by multi-subunit RNA polymerases date: 2020-07-01 words: 8442.0 sentences: 418.0 pages: flesch: 51.0 cache: ./cache/cord-103892-v6gkubd4.txt txt: ./txt/cord-103892-v6gkubd4.txt summary: Overall, these data demonstrated that the enhanced or diminished capabilities of the variant RNAPs to utilize 2''dGTP in the SNA assays reflected, in qualitative terms, their capabilities to utilize all four 2''dNTPs. The role of the β''Arg425 in selectively promoting the binding of NTPs was easy to explain because the β''Arg425 interacts with the 2''OH of the NTP analogues in several RNAP structures (Supplementary Table 5 , Fig. 1c, 4a, b) . We further hypothesized and demonstrated by in silico docking experiments that the 3''OH could move to within the hydrogen bond distance of the β''Arg425 if the deoxyribose moiety adopted a 2''-endo conformation (Supplementary Fig. 8 To test this hypothesis in crystallo, we solved the X-ray crystal structure of the initially transcribing complexes containing T. Overall, the comparative analysis of RNAP structures with CMPCPP, 2''dCTP and 3''dCTP suggested that the β''Arg425 inhibited the incorporation of 2''dNTPs by interacting with their 3''OH group and favoring the 2''-endo conformation of the deoxyribose moiety. abstract: RNA polymerases (RNAPs) synthesize RNA from NTPs, whereas DNA polymerases synthesize DNA from 2’dNTPs. DNA polymerases select against NTPs by using steric gates to exclude the 2’ OH, but RNAPs have to employ alternative selection strategies. In single-subunit RNAPs, a conserved Tyr residue discriminates against 2’dNTPs, whereas selectivity mechanisms of multi-subunit RNAPs remain hitherto unknown. Here we show that a conserved Arg residue uses a two-pronged strategy to select against 2’dNTPs in multi-subunit RNAPs. The conserved Arg interacts with the 2’OH group to promote NTP binding, but selectively inhibits incorporation of 2’dNTPs by interacting with their 3’OH group to favor the catalytically-inert 2’-endo conformation of the deoxyribose moiety. This deformative action is an elegant example of an active selection against a substrate that is a substructure of the correct substrate. Our findings provide important insights into the evolutionary origins of biopolymers and the design of selective inhibitors of viral RNAPs. url: https://doi.org/10.1101/2020.06.30.179606 doi: 10.1101/2020.06.30.179606 id: cord-103781-bycskjtr author: Mönke, Gregor title: Optimal time frequency analysis for biological data - pyBOAT date: 2020-06-04 words: 7386.0 sentences: 451.0 pages: flesch: 54.0 cache: ./cache/cord-103781-bycskjtr.txt txt: ./txt/cord-103781-bycskjtr.txt summary: With this challenge in mind, we have developed pyBOAT, a Python-based fully automatic stand-alone software that integrates multiple steps of non-stationary oscillatory time series analysis into an easy-to-use graphical user interface. Our approach integrates data-visualization, optimized sinc-filter detrending, amplitude envelope removal and a subsequent continuous-wavelet based time-frequency analysis. Computational methods that enable analysis of periods, amplitudes and phases of rhythmic time series data have been essential to unravel function and design principles of biological clocks (Lauschke et al. This allows to use a straightforward numerical method to estimate a lter response | w(ω)| 2 , i.e. applying the smoothing operation to simulated white noise and time averaging the Wavelet spectra. Continuous wavelet analysis allows to reveal non-stationary period, amplitude and phase dynamics and to identify multiple frequency components across dierent scales within a single oscillatory signal (Leise [2013] , Leise et al. abstract: Methods for the quantification of rhythmic biological signals have been essential for the discovery of function and design of biological oscillators. Advances in live measurements have allowed recordings of unprecedented resolution revealing a new world of complex heterogeneous oscillations with multiple noisy non-stationary features. However, our understanding of the underlying mechanisms regulating these oscillations has been lagging behind, partially due to the lack of simple tools to reliably quantify these complex non-stationary features. With this challenge in mind, we have developed pyBOAT, a Python-based fully automatic stand-alone software that integrates multiple steps of non-stationary oscillatory time series analysis into an easy-to-use graphical user interface. pyBOAT implements continuous wavelet analysis which is specifically designed to reveal time-dependent features. In this work we illustrate the advantages of our tool by analyzing complex non-stationary time-series profiles. Our approach integrates data-visualization, optimized sinc-filter detrending, amplitude envelope removal and a subsequent continuous-wavelet based time-frequency analysis. Finally, using analytical considerations and numerical simulations we discuss unexpected pitfalls in commonly used smoothing and detrending operations. url: https://doi.org/10.1101/2020.04.29.067744 doi: 10.1101/2020.04.29.067744 id: cord-352943-ztonp62x author: Nagpal, Sunil title: What if we perceive SARS-CoV-2 genomes as documents? Topic modelling using Latent Dirichlet Allocation to identify mutation signatures and classify SARS-CoV-2 genomes date: 2020-08-20 words: 2776.0 sentences: 174.0 pages: flesch: 47.0 cache: ./cache/cord-352943-ztonp62x.txt txt: ./txt/cord-352943-ztonp62x.txt summary: Here we describe how SARS-CoV-2 genomic mutation profiles can be structured into a ''Bag of Words'' to enable identification of signatures (topics) and their probabilistic distribution across various genomes using LDA. Use of the non-phylogenetic albeit classical approaches like topic modeling and other data centric pattern mining algorithms is therefore proposed for supplementing the efforts towards understanding the genomic diversity of the evolving SARS-CoV-2 genomes (and other pathogens/microbes). In fact, Latent Dirichlet Allocation (LDA), an unsupervised machine learning approach, is particularly known for identifying latent topics in large document collections and deciphering the words that define the inferred topics using a generative statistical model. Classical LDA was employed to generate topic models leading to identification of 16 amino acid mutation signatures and 18 nucleotide mutation signatures (equivalent to topics) in the corpus of chosen genomes through rigorous hyper-parameter tuning for coherence optimization (Figure 2) . abstract: Topic modeling is frequently employed for discovering structures (or patterns) in a corpus of documents. Its utility in text-mining and document retrieval tasks in various fields of scientific research is rather well known. An unsupervised machine learning approach, Latent Dirichlet Allocation (LDA) has particularly been utilized for identifying latent (or hidden) topics in document collections and for deciphering the words that define one or more topics using a generative statistical model. Here we describe how SARS-CoV-2 genomic mutation profiles can be structured into a ‘Bag of Words’ to enable identification of signatures (topics) and their probabilistic distribution across various genomes using LDA. Topic models were generated using ~47000 novel corona virus genomes (considered as documents), leading to identification of 16 amino acid mutation signatures and 18 nucleotide mutation signatures (equivalent to topics) in the corpus of chosen genomes through coherence optimization. The document assumption for genomes also helped in identification of contextual nucleotide mutation signatures in the form of conventional N-grams (e.g. bi-grams and tri-grams). We validated the signatures obtained using LDA driven method against the previously reported recurrent mutations and phylogenetic clades for genomes. Additionally, we report the geographical distribution of the identified mutation signatures in SARS-CoV-2 genomes on the global map. Use of the non-phylogenetic albeit classical approaches like topic modeling and other data centric pattern mining algorithms is therefore proposed for supplementing the efforts towards understanding the genomic diversity of the evolving SARS-CoV-2 genomes (and other pathogens/microbes). url: https://doi.org/10.1101/2020.08.20.258772 doi: 10.1101/2020.08.20.258772 id: cord-103343-k4v5ksvq author: Naim, Nikki title: NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity date: 2020-09-11 words: 823.0 sentences: 62.0 pages: flesch: 54.0 cache: ./cache/cord-103343-k4v5ksvq.txt txt: ./txt/cord-103343-k4v5ksvq.txt summary: title: NHR-49 Acts in Distinct Tissues to Promote Longevity versus Innate Immunity Aging and immunity are inextricably linked and many genes that extend lifespan also enhance immunoresistance. Here, we demonstrate that the Caenorhabditis elegans pro-longevity factor, NHR-49, also promotes resistance against Pseudomonas aeruginosa, but modulates immunity and longevity by spatially and mechanistically distinct mechanisms. NHR-49 expression is increased by germline ablation, an intervention that extends lifespan, but lowered by pathogen exposure. NHR-49 acted in multiple somatic tissues to promote longevity, whereas, it''s pro-immunity function was mediated by neuronal expression. Thus, NHR-49 targets share the largest overlap with genes whose 182 In this study, we demonstrate that NHR-49 is a pro-longevity factor that modulates 368 lifespan and immunity through distinct mechanisms. In fertile, nhr-49 single 393 mutants, immunity was restored by presence in neurons or intestine, but lifespan 394 could be rescued from other tissues as well. elegans lifespan in a NHR-49/PPARalpha-dependent manner abstract: Aging and immunity are inextricably linked and many genes that extend lifespan also enhance immunoresistance. However, it remains unclear if longevity-enhancing factors modulate immunity and longevity by distinct or shared mechanisms. Here, we demonstrate that the Caenorhabditis elegans pro-longevity factor, NHR-49, also promotes resistance against Pseudomonas aeruginosa, but modulates immunity and longevity by spatially and mechanistically distinct mechanisms. Fenofibrate, an agonist of NHR-49’s mammalian functional homolog, PPARα, enhanced worm immunoresistance in an NHR-49-dependent manner. NHR-49 expression is increased by germline ablation, an intervention that extends lifespan, but lowered by pathogen exposure. NHR-49 acted in multiple somatic tissues to promote longevity, whereas, it’s pro-immunity function was mediated by neuronal expression. The canonical NHR-49 target genes, acs-2 and fmo-2, were upregulated by germline loss, but infection triggered fmo-2 downregulation and acs-2 upregulation. Interestingly, neither gene conferred resistance against Gram-negative Pseudomonas, unlike their reported roles in immunity against Gram-positive pathogens. Thus, NHR-49 is differentially regulated by interventions that bring about long-term changes (lifespan extension) vs. short-term stress (pathogen exposure) and in response it orchestrates distinct outputs, including pathogen-specific transcriptional programs. Overall, our study demonstrates the independent control of immunity and longevity by a conserved regulatory protein. url: https://doi.org/10.1101/2020.09.11.290452 doi: 10.1101/2020.09.11.290452 id: cord-301233-nenw0f81 author: Naydenova, Katerina title: Structural basis for the inhibition of the SARS-CoV-2 RNA-dependent RNA polymerase by favipiravir-RTP date: 2020-10-21 words: 4059.0 sentences: 217.0 pages: flesch: 51.0 cache: ./cache/cord-301233-nenw0f81.txt txt: ./txt/cord-301233-nenw0f81.txt summary: Here we report the structure of favipiravir ribonucleoside triphosphate (favipiravir-RTP) in complex with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) bound to a template:primer RNA duplex, determined by electron cryomicroscopy (cryoEM) to a resolution of 2.5 Å. The structure reveals an unusual, non-productive binding mode of favipiravir-RTP at the catalytic site of SARS-CoV-2 RdRp which explains its low rate of incorporation into the RNA primer strand. Here we report the structure of the SARS-CoV-2 RdRp, comprising subunits nsp7, nsp8 and nsp12, in complex with template:primer double-stranded RNA and favipiravir ribonucleoside triphosphate (favipiravir-RTP), determined by cryoEM at 2.5Å resolution. In this study, we determined the cryoEM structure of favipiravir-RTP at the catalytic site of the SARS-CoV-2 RdRp, in complex with template:primer dsRNA, and investigated the influence of this nucleotide analogue inhibitor on RNA synthesis in vitro. abstract: The RNA polymerase inhibitor, favipiravir, is currently in clinical trials as a treatment for infection with SARS-CoV-2, despite limited information about the molecular basis for its activity. Here we report the structure of favipiravir ribonucleoside triphosphate (favipiravir-RTP) in complex with the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) bound to a template:primer RNA duplex, determined by electron cryomicroscopy (cryoEM) to a resolution of 2.5 Å. The structure shows clear evidence for the inhibitor at the catalytic site of the enzyme, and resolves the conformation of key side chains and ions surrounding the binding pocket. Polymerase activity assays indicate that the inhibitor is weakly incorporated into the RNA primer strand, and suppresses RNA replication in the presence of natural nucleotides. The structure reveals an unusual, non-productive binding mode of favipiravir-RTP at the catalytic site of SARS-CoV-2 RdRp which explains its low rate of incorporation into the RNA primer strand. Together, these findings inform current and future efforts to develop polymerase inhibitors for SARS coronaviruses. url: https://doi.org/10.1101/2020.10.21.347690 doi: 10.1101/2020.10.21.347690 id: cord-279629-t1xjy12y author: Nazneen Akhand, Mst Rubaiat title: Genome based Evolutionary study of SARS-CoV-2 towards the Prediction of Epitope Based Chimeric Vaccine date: 2020-04-15 words: 6717.0 sentences: 379.0 pages: flesch: 47.0 cache: ./cache/cord-279629-t1xjy12y.txt txt: ./txt/cord-279629-t1xjy12y.txt summary: The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Hence, the study was designed to develop a chimeric recombinant vaccine against COVID-19 by targeting four major structural proteins of the pathogen, while revealing the evolutionary history of different species of coronavirus based on whole genome and protein domain-based phylogeny. Apart from the human coronaviruses, we introduced other coronaviruses which choose different species of bats, whale, turkey, rat, mink, ferret, swine, camel, rabbit, cow and others as host (Supplementary TableDomain analysis of spike protein of coronaviruses reveals that they contain mainly one signature domains namely, coronavirus S2 glycoprotein (IPR002552), which is present in all the candidates. Design of an epitope-based peptide vaccine against spike protein of human coronavirus: an in silico approach. abstract: SARS-CoV-2 is known to infect the neurological, respiratory, enteric, and hepatic systems of human and has already become an unprecedented threat to global healthcare system. COVID-19, the most serious public condition caused by SARS-CoV-2 leads the world to an uncertainty alongside thousands of regular death scenes. Unavailability of specific therapeutics or approved vaccine has made the recovery of COVI-19 more troublesome and challenging. The present in silico study aimed to predict a novel chimeric vaccines by simultaneously targeting four major structural proteins via the establishment of ancestral relationship among different strains of coronaviruses. Conserved regions from the homologous protein sets of spike glycoprotein (S), membrane protein (M), envelope protein and nucleocapsid protein (N) were identified through multiple sequence alignment. The phylogeny analyses of whole genome stated that four proteins (S, E, M and N) reflected the close ancestral relation of SARS-CoV-2 to SARS-COV-1 and bat coronavirus. Numerous immunogenic epitopes (both T cell and B cell) were generated from the common fragments which were further ranked on the basis of antigenicity, transmembrane topology, conservancy level, toxicity and allergenicity pattern and population coverage analysis. Top putative epitopes were combined with appropriate adjuvants and linkers to construct a novel multiepitope subunit vaccine against COVID-19. The designed constructs were characterized based on physicochemical properties, allergenicity, antigenicity and solubility which revealed the superiority of construct V3 in terms safety and efficacy. Essential molecular dynamics and Normal Mode analysis confirmed minimal deformability of the refined model at molecular level. In addition, disulfide engineering was investigated to accelerate the stability of the protein. Molecular docking study ensured high binding affinity between construct V3 and HLA cells, as well as with different host receptors. Microbial expression and translational efficacy of the constructs were checked using pET28a(+) vector of E. coli strain K12. The development of preventive measures to combat COVID-19 infections might be aided the present study. However, the in vivo and in vitro validation might be ensured with wet lab trials using model animals for the implementation of the presented data. url: https://doi.org/10.1101/2020.04.15.036285 doi: 10.1101/2020.04.15.036285 id: cord-291420-40xsypzt author: Nelson-Sathi, Shijulal title: Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction date: 2020-10-01 words: 2274.0 sentences: 145.0 pages: flesch: 54.0 cache: ./cache/cord-291420-40xsypzt.txt txt: ./txt/cord-291420-40xsypzt.txt summary: title: Mutational landscape and in silico structure models of SARS-CoV-2 Spike Receptor Binding Domain reveal key molecular determinants for virus-host interaction Formation of a stable binding interface between the Spike (S) protein Receptor Binding Domain (RBD) of SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) of host actuates viral entry. In silico structure modelling of interfaces induced by mutations on residues which directly engage ACE2 or lie in the near vicinity revealed molecular rearrangements and binding energies unique to each RBD mutant. The structural analysis of the mutated spike glycoprotein of SARS-CoV-2 RBD domain was done to assess the impact of interface amino acid residue mutations on binding affinity towards the human ACE2 (hACE2) receptor. Comparative analysis of structures showed key differences in all three binding clusters of SARS-CoV-2 RBD wild type and mutant interfaces with human or mouse ACE2 (Figure 2C, 2D and Table S1 ). abstract: Protein-protein interactions between virus and host are crucial for infection. SARS-CoV-2, the causative agent of COVID-19 pandemic is an RNA virus prone to mutations. Formation of a stable binding interface between the Spike (S) protein Receptor Binding Domain (RBD) of SARS-CoV-2 and Angiotensin-Converting Enzyme 2 (ACE2) of host actuates viral entry. Yet, how this binding interface evolves as virus acquires mutations during pandemic remains elusive. Here, using a high fidelity bioinformatics pipeline, we analysed 31,403 SARS-CoV-2 genomes across the globe, and identified 444 non-synonymous mutations that cause 49 distinct amino acid substitutions in the RBD. Molecular phylogenetic analysis suggested independent emergence of these RBD mutants during pandemic. In silico structure modelling of interfaces induced by mutations on residues which directly engage ACE2 or lie in the near vicinity revealed molecular rearrangements and binding energies unique to each RBD mutant. Comparative structure analysis using binding interface from mouse that prevents SARS-CoV-2 entry uncovered minimal molecular determinants in RBD necessary for the formation of stable interface. We identified that interfacial interaction involving amino acid residues N487 and G496 on either ends of the binding scaffold are indispensable to anchor RBD and are well conserved in all SARS-like corona viruses. All other interactions appear to be required to locally remodel binding interface with varying affinities and thus may decide extent of viral transmission and disease outcome. Together, our findings propose the modalities and variations in RBD-ACE2 interface formation exploited by SARS-CoV-2 for endurance. Importance COVID-19, so far the worst hit pandemic to mankind, started in January 2020 and is still prevailing globally. Our study identified key molecular arrangements in RBD-ACE2 interface that help virus to tolerate mutations and prevail. In addition, RBD mutations identified in this study can serve as a molecular directory for experimental biologists to perform functional validation experiments. The minimal molecular requirements for the formation of RBD-ACE2 interface predicted using in silico structure models may help precisely design neutralizing antibodies, vaccines and therapeutics. Our study also proposes the significance of understanding evolution of protein interfaces during pandemic. url: https://doi.org/10.1101/2020.05.02.071811 doi: 10.1101/2020.05.02.071811 id: cord-336628-0evl3wnd author: Neufeldt, Christopher J. title: SARS-CoV-2 infection induces a pro-inflammatory cytokine response through cGAS-STING and NF-κB date: 2020-07-21 words: 5880.0 sentences: 362.0 pages: flesch: 49.0 cache: ./cache/cord-336628-0evl3wnd.txt txt: ./txt/cord-336628-0evl3wnd.txt summary: Consistently, secreted cytokine profiles from both severe COVID-19 patients and SARS-CoV-2 infected lung epithelial cells, were enriched for pro-inflammatory cytokines and lacked type I/III IFNs. We also demonstrate that SARS-CoV-2 infection leads specifically to NF-κB but not IRF3 nuclear localization and that poly(I:C)-induced pathway activation is attenuated in infected cells. To confirm that the lack of IFN response in Calu-3 or A549-ACE2 cells infected with SARS-CoV-2 was not due to defects in the activation of innate immune pathways, we To test if IFNs could limit virus replication even after establishment of infection, A549-ACE2 cells were treated with high levels of various IFNs at the time point of infection or 6 h thereafter. these results indicate that SARS-CoV2-infection triggers the cGAS-STING pathway, leading to NF-κB-mediated induction of pro-inflammatory cytokines, and that this response can be controlled with STING inhibitors. abstract: SARS-CoV-2 is a novel virus that has rapidly spread, causing a global pandemic. In the majority of infected patients, SARS-CoV-2 leads to mild disease; however, in a significant proportion of infections, individuals develop severe symptoms that can lead to permanent lung damage or death. These severe cases are often associated with high levels of pro-inflammatory cytokines and low antiviral responses which can lead to systemic complications. We have evaluated transcriptional and cytokine secretion profiles from infected cell cultures and detected a distinct upregulation of inflammatory cytokines that parallels samples taken from infected patients. Building on these observations, we found a specific activation of NF-κB and a block of IRF3 nuclear translocation in SARS-CoV-2 infected cells. This NF-κB response is mediated by cGAS-STING activation and could be attenuated through STING targeting drugs. Our results show that SARS-CoV-2 curates a cGAS-STING mediated NF-κB driven inflammatory immune response in epithelial cells that likely contributes to inflammatory responses seen in patients and might be a target to suppress severe disease symptoms. url: https://doi.org/10.1101/2020.07.21.212639 doi: 10.1101/2020.07.21.212639 id: cord-103638-n5kpvsvg author: Nguyen, Long T. title: Enhancement of trans-cleavage activity of Cas12a with engineered crRNA enables amplified nucleic acid detection date: 2020-04-14 words: 5357.0 sentences: 388.0 pages: flesch: 60.0 cache: ./cache/cord-103638-n5kpvsvg.txt txt: ./txt/cord-103638-n5kpvsvg.txt summary: By extending the 3''or 5''-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discovered a new self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs were incorporated in a paper-based lateral flow assay that could detect the target with up to 23-fold higher sensitivity within 40-60 minutes. However, the ENHANCE showed 5.4-fold and 3.4-fold and higher trans-cleavage activity compared to the wild-type crRNA for targeting the methylated dsDNA and ssDNA, respectively (Fig. 3e, Supplementary Fig. 20a) . While no clinical samples were tested, the results indicated the 3''DNA7-modified crRNA consistently demonstrated higher sensitivity for detecting CoV-2 dsDNA within 30 minutes as compared to the wild-type crCoV-2 ( Supplementary Figs. abstract: The CRISPR/Cas12a RNA-guided complexes have a tremendous potential for nucleic acid detection due to its ability to indiscriminately cleave ssDNA once bound to a target DNA. However, the current CRISPR/Cas12a systems are limited to detecting DNA in a picomolar detection limit without an amplification step. Here, we developed a platform with engineered crRNAs and optimized conditions that enabled us to detect DNA, DNA/RNA heteroduplex and methylated DNA with higher sensitivity, achieving a limit of detection of in femtomolar range without any target pre-amplification step. By extending the 3’- or 5’-ends of the crRNA with different lengths of ssDNA, ssRNA, and phosphorothioate ssDNA, we discovered a new self-catalytic behavior and an augmented rate of LbCas12a-mediated collateral cleavage activity as high as 3.5-fold compared to the wild-type crRNA. We applied this sensitive system to detect as low as 25 fM dsDNA from the PCA3 gene, an overexpressed biomarker in prostate cancer patients, in simulated urine over 6 hours. The same platform was used to detect as low as ~700 fM cDNA from HIV, 290 fM RNA from HCV, and 370 fM cDNA from SARS-CoV-2, all within 30 minutes without a need for target amplification. With isothermal amplification of SARS-CoV-2 RNA using RT-LAMP, the modified crRNAs were incorporated in a paper-based lateral flow assay that could detect the target with up to 23-fold higher sensitivity within 40-60 minutes. url: https://doi.org/10.1101/2020.04.13.036079 doi: 10.1101/2020.04.13.036079 id: cord-255371-o9oxchq6 author: Nguyen, Thanh Thi title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) date: 2020-07-10 words: 5640.0 sentences: 365.0 pages: flesch: 59.0 cache: ./cache/cord-255371-o9oxchq6.txt txt: ./txt/cord-255371-o9oxchq6.txt summary: title: Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus) This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. We use 6,324 SARS-CoV-2 genome sequences collected in 45 countries and deposited to the NCBI GenBank so far and create a spreadsheet dataset of all mutations occurred across different genes. In this paper, to evaluate the possible impacts of genomic mutations on the virus functions, we propose the use of the SSpro/ACCpro 5 methods to predict protein secondary structure and relative solvent accessibility [13] . By comparing the prediction results obtained on the reference genome and mutated genomes, we are able to assess whether the detected mutations have the potential to change the protein structure and solvent accessibility, and thus lead to possible changes of the virus characteristics. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development. url: https://doi.org/10.1101/2020.07.10.171769 doi: 10.1101/2020.07.10.171769 id: cord-291523-4dtk1kyh author: Nguyen, Thanh Thi title: Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence date: 2020-07-01 words: 5361.0 sentences: 313.0 pages: flesch: 62.0 cache: ./cache/cord-291523-4dtk1kyh.txt txt: ./txt/cord-291523-4dtk1kyh.txt summary: Outcomes of a phylogenetic analysis suggest that the virus belongs to the genus Betacoronavirus, sub-genus Sarbecovirus, which includes many bat SARS-like CoVs and SARS CoVs. Another study in [5] confirms this finding by analysing genomes obtained from three adult patients admitted to a hospital in Wuhan on December 27, 2019. With the cut-off parameter C is set equal to 0.7, the hierarchical clustering algorithm separates the reference sequences into 6 clusters in which cluster "5" comprises all examined viruses of the Sarbecovirus sub-genus, including many SARS CoVs, bat SARS-like CoVs and pangolin CoVs (Fig. 7A) . With the results obtained in Fig. 7D (and also in the experiments with the DBSCAN method presented next), we support a hypothesis that bats or pangolins are the probable origin of SARS-CoV-2. In this Appendix, we first present results of the hierarchical clustering method applied to the dataset that combines Set 1 of reference sequences (Table 1 ) with all 334 SARS-CoV-2 sequences (see Fig. 9 ). abstract: Origin of the COVID-19 virus has been intensely debated in the scientific community since the first infected cases were detected in December 2019. The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins. url: https://doi.org/10.1101/2020.05.12.091397 doi: 10.1101/2020.05.12.091397 id: cord-102823-zult69f2 author: Nguyen, Thin title: GraphDTA: Predicting drug–target binding affinity with graph neural networks date: 2020-10-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The development of new drugs is costly, time consuming, and often accompanied with safety issues. Drug repurposing can avoid the expensive and lengthy process of drug development by finding new uses for already approved drugs. In order to repurpose drugs effectively, it is useful to know which proteins are targeted by which drugs. Computational models that estimate the interaction strength of new drug--target pairs have the potential to expedite drug repurposing. Several models have been proposed for this task. However, these models represent the drugs as strings, which is not a natural way to represent molecules. We propose a new model called GraphDTA that represents drugs as graphs and uses graph neural networks to predict drug--target affinity. We show that graph neural networks not only predict drug--target affinity better than non-deep learning models, but also outperform competing deep learning methods. Our results confirm that deep learning models are appropriate for drug--target binding affinity prediction, and that representing drugs as graphs can lead to further improvements. Availability of data and materials The proposed models are implemented in Python. Related data, pre-trained models, and source code are publicly available at https://github.com/thinng/GraphDTA. All scripts and data needed to reproduce the post-hoc statistical analysis are available from https://doi.org/10.5281/zenodo.3603523. Contact Thin.Nguyen@deakin.edu.au url: https://doi.org/10.1101/684662 doi: 10.1101/684662 id: cord-268894-amfv3z2y author: Nguyen-Contant, Phuong title: S protein-reactive IgG and memory B cell production after human SARS-CoV-2 infection includes broad reactivity to the S2 subunit date: 2020-07-21 words: 4632.0 sentences: 269.0 pages: flesch: 56.0 cache: ./cache/cord-268894-amfv3z2y.txt txt: ./txt/cord-268894-amfv3z2y.txt summary: Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD 31 and S2 subunit, and nucleocapsid [N] ) and non-SARS-CoV-2 proteins were related to 32 measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD 31 and S2 subunit, and nucleocapsid [N] ) and non-SARS-CoV-2 proteins were related to 32 measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Approximately one-third of non-SARS-CoV-140 2-exposed subjects in the healthy donor cohort had low levels of serum IgG against the S and N 141 proteins of SARS-CoV-2, likely reflecting cross-reactivity with seasonal HCoVs ( Figure 1A ). In contrast, IgG MBCs reactive to the S proteins of the HCoVs OC43 and 229E 192 and the control proteins H1 and TTd were detected in nearly 50% or more of non-SARS-CoV-2-193 exposed subjects, consistent with the higher levels of serum IgG against these antigens ( Figure 2E -194 2H) . abstract: The high susceptibility of humans to SARS-CoV-2 infection, the cause of COVID-19, reflects the novelty of the virus and limited preexisting B cell immunity. IgG against the SARS-CoV-2 spike (S) protein, which carries the novel receptor binding domain (RBD), is absent or at low levels in unexposed individuals. To better understand the B cell response to SARS-CoV-2 infection, we asked whether virus-reactive memory B cells (MBCs) were present in unexposed subjects and whether MBC generation accompanied virus-specific IgG production in infected subjects. We analyzed sera and PBMCs from non-SARS-CoV-2-exposed healthy donors and COVID-19 convalescent subjects. Serum IgG levels specific for SARS-CoV-2 proteins (S, including the RBD and S2 subunit, and nucleocapsid [N]) and non-SARS-CoV-2 proteins were related to measurements of circulating IgG MBCs. Anti-RBD IgG was absent in unexposed subjects. Most unexposed subjects had anti-S2 IgG and a minority had anti-N IgG, but IgG MBCs with these specificities were not detected, perhaps reflecting low frequencies. Convalescent subjects had high levels of IgG against the RBD, S2, and N, together with large populations of RBD- and S2-reactive IgG MBCs. Notably, IgG titers against the S protein of the human coronavirus OC43 in convalescent subjects were higher than in unexposed subjects and correlated strongly with anti-S2 titers. Our findings indicate cross-reactive B cell responses against the S2 subunit that might enhance broad coronavirus protection. Importantly, our demonstration of MBC induction by SARS-CoV-2 infection suggests that a durable form of B cell immunity is maintained even if circulating antibody levels wane. IMPORTANCE Recent rapid worldwide spread of SARS-CoV-2 has established a pandemic of potentially serious disease in the highly susceptible human population. Key questions are whether humans have preexisting immune memory that provides some protection against SARS-CoV-2 and whether SARS-CoV-2 infection generates lasting immune protection against reinfection. Our analysis focused on pre- and post-infection IgG and IgG memory B cells (MBCs) reactive to SARS-CoV-2 proteins. Most importantly, we demonstrate that infection generates both IgG and IgG MBCs against the novel receptor binding domain and the conserved S2 subunit of the SARS-CoV-2 spike protein. Thus, even if antibody levels wane, long-lived MBCs remain to mediate rapid antibody production. Our study also suggests that SARS-CoV-2 infection strengthens preexisting broad coronavirus protection through S2-reactive antibody and MBC formation. url: https://doi.org/10.1101/2020.07.20.213298 doi: 10.1101/2020.07.20.213298 id: cord-103703-t03r6ny8 author: Nguyen-Tu, Marie-Sophie title: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice date: 2020-05-20 words: 6230.0 sentences: 300.0 pages: flesch: 50.0 cache: ./cache/cord-103703-t03r6ny8.txt txt: ./txt/cord-103703-t03r6ny8.txt summary: title: Reduced expression of TCF7L2 in adipocyte impairs glucose tolerance associated with decreased insulin secretion, incretins levels and lipid metabolism dysregulation in male mice Mice with biallelic Tcf7l2 deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reduced in vivo glucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Therefore, alterations in pancreatic beta cell function observed ex vivo in the absence of TCF7L2 in adipocyte have no impact on whole body glucose-stimulated insulin secretion. A striking finding in the present study is that TCF7L2 is required in adipose tissue for normal incretin production and insulin secretion: we reveal that decreased Tcf7l2 expression in mature adipocytes leads to lowered circulating levels of GLP-1 and GIP ( Fig.4a and b) . abstract: Transcription factor 7-like 2 (TCF7L2) is a downstream effector of the Wnt/beta-catenin signalling pathway and its expression is critical for adipocyte development. The precise role of TCF7L2 in glucose and lipid metabolism in adult adipocytes remains to be defined. Here, we aim to investigate how changes in TCF7L2 expression in mature adipocytes affect glucose homeostasis. Tcf7l2 was selectively ablated from mature adipocytes in C57BL/6J mice using an adiponectin promoter-driven Cre recombinase to recombine alleles floxed at exon 1 of the Tcf7l2 gene. Mice lacking Tcf7l2 in mature adipocytes displayed normal body weight. Male mice exhibited normal glucose homeostasis at eight weeks of age. Male heterozygote knockout mice (aTCF7L2het) exhibited impaired glucose tolerance (AUC increased 1.14 ± 0.04 -fold, p=0.03), as assessed by intraperitoneal glucose tolerance test, and changes in fat mass at 16 weeks (increased by 1.4 ± 0.09-fold, p=0.007). Homozygote knockout mice exhibited impaired oral glucose tolerance at 16 weeks of age (AUC increased 2.15 ± 0.15-fold, p=0.0001). Islets of Langerhans exhibited impaired glucose-stimulated insulin secretion in vitro (decreased 0.54 ± 0.13-fold aTCF7L2KO vs control, p=0.02), but no changes in in vivo glucose-stimulated insulin secretion. Female mice in which one or two alleles of the Tcf7l2 gene was knocked out in adipocytes displayed no changes in glucose tolerance, insulin sensitivity or insulin secretion. Plasma levels of glucagon-like peptide-1 and gastric inhibitory polypeptide were lowered in knockout mice (decreased 0.57 ± 0.03-fold and 0.41 ± 0.12-fold, p=0.04 and p=0.002, respectively), whilst plasma free fatty acids and Fatty Acid Binding Protein 4 circulating levels were increased by 1.27 ± 0.07 and 1.78 ± 0.32-fold, respectively (p=0.05 and p=0.03). Mice with biallelic Tcf7l2 deletion exposed to high fat diet for 9 weeks exhibited impaired glucose tolerance (p=0.003 at 15 min after glucose injection) which was associated with reduced in vivo glucose-stimulated insulin secretion (decreased 0.51 ± 0.03-fold, p=0.02). Thus, our data indicate that loss of Tcf7l2 gene expression in adipocytes leads to impairments on metabolic responses which are dependent on gender, age and nutritional status. Our findings further illuminate the role of TCF7L2 in the maintenance of glucose homeostasis. url: https://doi.org/10.1101/2020.05.18.102384 doi: 10.1101/2020.05.18.102384 id: cord-323828-ug2duzw1 author: Ni, Dongchun title: Structural investigation of ACE2 dependent disassembly of the trimeric SARS-CoV-2 Spike glycoprotein date: 2020-10-12 words: 3408.0 sentences: 234.0 pages: flesch: 65.0 cache: ./cache/cord-323828-ug2duzw1.txt txt: ./txt/cord-323828-ug2duzw1.txt summary: Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. The clinical-grade soluble form of hACE2 has been reported to be a 74 potential novel therapeutic approach for reducing the infection of SARS-CoV-2 (Monteil et al., 2020) by preventing the viral Spike from interacting with other hACE2 present on human cells. The final 3D 115 reconstruction from 72''446 particles at 5.1Å overall resolution showed a density map corresponding to a single, 116 monomeric Spike protein in complex with hACE2 (Fig. 1a) . Figure 1 Cryo-EM maps of SARS-CoV-2 Spike-hACE2 complexes and fitted models. Cryo-EM structure of the SARS coronavirus spike glycoprotein in 352 complex with its host cell receptor ACE2 abstract: The human membrane protein Angiotensin-converting enzyme 2 (hACE2) acts as the main receptor for host cells invasion of the new coronavirus SARS-CoV-2. The viral surface glycoprotein Spike binds to hACE2, which triggers virus entry into cells. As of today, the role of hACE2 for virus fusion is not well understood. Blocking the transition of Spike from its prefusion to post-fusion state might be a strategy to prevent or treat COVID-19. Here we report a single particle cryo-electron microscopy analysis of SARS-CoV-2 trimeric Spike in presence of the human ACE2 ectodomain. The binding of purified hACE2 ectodomain to Spike induces the disassembly of the trimeric form of Spike and a structural rearrangement of its S1 domain to form a stable, monomeric complex with hACE2. This observed hACE2 dependent dissociation of the Spike trimer suggests a mechanism for the therapeutic role of recombinant soluble hACE2 for treatment of COVID-19. url: https://doi.org/10.1101/2020.10.12.336016 doi: 10.1101/2020.10.12.336016 id: cord-298326-f5q7j3iu author: Nick, Benjamin C. title: Identification of a critical horseshoe-shaped region in the nsp5 (Mpro, 3CLpro) protease interdomain loop (IDL) of coronavirus mouse hepatitis virus (MHV) date: 2020-06-19 words: 2755.0 sentences: 118.0 pages: flesch: 54.0 cache: ./cache/cord-298326-f5q7j3iu.txt txt: ./txt/cord-298326-f5q7j3iu.txt summary: In this study, we describe the identification of an essential, conserved horseshoe-shaped region in the nsp5 interdomain loop (IDL) of mouse hepatitis virus (MHV), a common coronavirus replication model. Structural modeling and sequence analysis of these sites in other coronaviruses, including all 7 human coronaviruses, suggests that the identified structure and sequence of this horseshoe regions is highly conserved and may represent a new, non-active-site regulatory region of the nsp5 (3CLpro) protease to target with coronavirus inhibitors. To evaluate whether any of 207 the recovered MHV nsp5 IDL mutants may exhibit a temperature-sensitive phenotype, we 208 performed an efficiency of plating (EOP) analysis by comparing the titers of each IDL virus by 209 plaque assay determined at a physiologic (37°C) and elevated temperature (40°C) (Fig. 3A) . abstract: Human coronaviruses are enveloped, positive-strand RNA viruses which cause respiratory diseases ranging in severity from the seasonal common cold to SARS and COVID-19. Of the 7 human coronaviruses discovered to date, 3 emergent and severe human coronavirus strains (SARS-CoV, MERS-CoV, and SARS-CoV-2) have recently jumped to humans in the last 20 years. The COVID-19 pandemic spawned by the emergence of SARS-CoV-2 in late 2019 has highlighted the importance for development of effective therapeutics to target emerging coronaviruses. Upon entry, the replicase genes of coronaviruses are translated and subsequently proteolytically processed by virus-encoded proteases. Of these proteases, nonstructural protein 5 (nsp5, Mpro, or 3CLpro), mediates the majority of these cleavages and remains a key drug target for therapeutic inhibitors. Efforts to develop nsp5 active-site inhibitors for human coronaviruses have thus far been unsuccessful, establishing the need for identification of other critical and conserved non-active-site regions of the protease. In this study, we describe the identification of an essential, conserved horseshoe-shaped region in the nsp5 interdomain loop (IDL) of mouse hepatitis virus (MHV), a common coronavirus replication model. Using site-directed mutagenesis and replication studies, we show that several residues comprising this horseshoe-shaped region either fail to tolerate mutagenesis or were associated with viral temperature-sensitivity. Structural modeling and sequence analysis of these sites in other coronaviruses, including all 7 human coronaviruses, suggests that the identified structure and sequence of this horseshoe regions is highly conserved and may represent a new, non-active-site regulatory region of the nsp5 (3CLpro) protease to target with coronavirus inhibitors. Importance In December 2019, a novel coronavirus (SARS-CoV-2) emerged in humans and triggered a pandemic which has to date resulted in over 8 million confirmed cases of COVID-19 across more than 180 countries and territories (June 2020). SARS-CoV-2 represents the third emergent coronavirus in the past 20 years and the future emergence of new coronaviruses in humans remains certain. Critically, there remains no vaccine nor established therapeutics to treat cases of COVID-19. The coronavirus nsp5 protease is a conserved and indispensable virus-encoded enzyme which remains a key target for therapeutic design. However, past attempts to target the active site of nsp5 with inhibitors have failed stressing the need to identify new conserved non-active-site targets for therapeutic development. This study describes the discovery of a novel conserved structural region of the nsp5 protease of coronavirus mouse hepatitis virus (MHV) which may provide a new target for coronavirus drug development. url: https://doi.org/10.1101/2020.06.18.160671 doi: 10.1101/2020.06.18.160671 id: cord-282604-xp71rkxc author: Nikolaev, EN title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein date: 2020-05-25 words: 2181.0 sentences: 114.0 pages: flesch: 53.0 cache: ./cache/cord-282604-xp71rkxc.txt txt: ./txt/cord-282604-xp71rkxc.txt summary: title: Mass Spectrometric detection of SARS-CoV-2 virus in scrapings of the epithelium of the nasopharynx of infected patients via Nucleocapsid N protein We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. We have performed a pilot study on nasopharynx epithelial swabs already collected from patients with CODIV-19 for RT-qPCR and showed confident identification of the N protein of the SARS CoV-2 virus by mass-spectrometry with the use of a very basic sample preparation procedure. Mass Spectrometric Identification of SARS-CoV-2 Proteins from Gargle Solution Samples of COVID-19 Patients abstract: Detection of viral RNA by PCR is currently the main diagnostic tool for COVID-19 [1]. The PCR-based test, however, shows limited sensitivity, especially at early and late stages of the disease development [2,3], and is relatively time consuming. Fast and reliable complementary methods for detecting the viral infection would be of help in the current pandemia conditions. Mass-spectrometry is one of such possibilities. We have developed a mass-spectrometry based method for the detection of the SARS CoV-2 virus in nasopharynx epithelial swabs, based on the detection of the viral nucleocapsid N protein. The N protein of the SARS-COV-2 virus, the most abundant protein in the virion, is the best candidate for mass-spectrometric detection of the infection, and MS-based detection of several peptides from the SARS-COoV-2 nucleoprotein has been reported earlier by the Sinz group [4]. Our approach shows confident identification of the N protein in patient samples even with the lowest viral loads and a much simpler preparation procedure. Our main protocol consists of virus inactivation by heating and adding of isopropanol, and tryptic digestion of the proteins sedimented from the swabs followed by MS analysis. A set of unique peptides, produced as a result of proteolysis of the nucleocapsid phosphoprotein of SARS-CoV-2, is detected. The obtained results can further be used to create fast parallel mass-spectrometric approaches for the detection of the virus in the nasopharyngeal mucosa, saliva, sputum and other physiological fluids. url: https://doi.org/10.1101/2020.05.24.113043 doi: 10.1101/2020.05.24.113043 id: cord-104157-rivaoo73 author: Noreika, Valdas title: Alertness fluctuations during task performance modulate cortical evoked responses to transcranial magnetic stimulation date: 2019-06-28 words: 10469.0 sentences: 492.0 pages: flesch: 52.0 cache: ./cache/cord-104157-rivaoo73.txt txt: ./txt/cord-104157-rivaoo73.txt summary: We observed rapid, non-linear changes in TMS-evoked neural responses – specifically, motor evoked potentials and TMS-evoked cortical potentials – as EEG activity indicated decreasing levels of alertness, even while participants remained awake and responsive in the behavioural task. Here we combined single-pulse TMS with concurrent EEG recording and a simple behavioural task to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. To assess the instantaneous level of alertness, a two-fold EEG analysis was applied over the time window immediately preceding each TMS pulse: (1) a binary definition of awake and drowsy states following EEG spectral power signatures (θ/α) averaged across all EEG electrodes (Bareham et al., 2014) , and (2) a dynamical definition of alertness levels following a detailed sub-staging system for scoring the transition to N1 sleep (Hori et al., 1994) (Fig. 1C ). abstract: Transcranial magnetic stimulation (TMS) has been widely used in human cognitive neuroscience to examine the causal role of distinct cortical areas in perceptual, cognitive and motor functions. However, it is widely acknowledged that the effects of focal cortical stimulation on behaviour can vary substantially between participants and even from trial to trial within individuals. Here we asked whether spontaneous fluctuations in alertness can account for the variability in behavioural and neurophysiological responses to TMS. We combined single-pulse TMS with neural recording via electroencephalography (EEG) to quantify changes in motor and cortical reactivity with fluctuating levels of alertness defined objectively on the basis of ongoing brain activity. We observed rapid, non-linear changes in TMS-evoked neural responses – specifically, motor evoked potentials and TMS-evoked cortical potentials – as EEG activity indicated decreasing levels of alertness, even while participants remained awake and responsive in the behavioural task. IMPACT STATEMENT A substantial proportion of inter-trial variability in neurophysiological responses to TMS is due to spontaneous fluctuations in alertness, which should be controlled for during experimental and clinical applications of TMS. url: https://doi.org/10.1101/155754 doi: 10.1101/155754 id: cord-103812-ls6zgipi author: Norris, Rachael P. title: Gap junction internalization and processing in vivo: a 3D immuno-electron microscopy study date: 2020-06-30 words: 4803.0 sentences: 296.0 pages: flesch: 55.0 cache: ./cache/cord-103812-ls6zgipi.txt txt: ./txt/cord-103812-ls6zgipi.txt summary: Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Gap junction internalization can also be considered to be a form of trogocytosis (Joly and Hudriser, 2003) in which a portion of the plasma membrane and cytosol of the neighboring cell is transferred to the engulfing cell (See Fig. 1A ). Serial sections were then imaged to obtain threedimensional information; this distinguished between internalized connexosomes and gap junctions in the process of invagination. In 7 of the 56 modified connexosomes, a patch of unlabeled outer membrane bulged outward from a labeled inner membrane ( suggesting that different types of vesicles were involved. Five serial sections through a modified connexosome containing several internal vesicles labeled with Cx43. abstract: Gap junctions have well-established roles in cell-cell communication by way of forming permeable intercellular channels. Less is understood about their internalization, which forms double membrane vesicles containing cytosol and membranes from another cell, called connexosomes or annular gap junctions. Here, we systematically studied the fate of connexosomes in intact ovarian follicles. High pressure frozen, serial sectioned tissue was immunogold labeled for Connexin 43. Within a volume of electron micrographs, every labeled structure was categorized and counted. Surface area measurements indicate that large connexosomes undergo fission. Subsequent modifications are separation of inner and outer membranes, loss of Cx43 from the outer membrane, and outward budding of the modified membranes. We also documented several clear examples of organelle transfer from one cell to another by gap junction internalization. We discuss how connexosome formation and processing may be a novel means for gap junctions to mediate cell-cell communication. url: https://doi.org/10.1101/2020.06.29.178475 doi: 10.1101/2020.06.29.178475 id: cord-103294-1lrfna4v author: Northrop, Amanda C. title: Clockwise and counterclockwise hysteresis characterize state changes in the same aquatic ecosystem date: 2020-05-02 words: 596.0 sentences: 32.0 pages: flesch: 47.0 cache: ./cache/cord-103294-1lrfna4v.txt txt: ./txt/cord-103294-1lrfna4v.txt summary: A model system for understanding ecosystem recovery is the aquatic microecosystem that inhabits the cup-shaped leaves of the pitcher plant Sarracenia purpurea. At low enrichment rates, ecosystems showed a substantial lag in the recovery of [O2] (clockwise hysteresis). At high enrichment rates, we observed a novel response: changes in [O2] were proportionally larger during the recovery phase than during the enrichment phase (counter-clockwise hysteresis). With counter-clockwise hysteresis, rapid reduction of a driver variable following high enrichment rates may be a viable restoration strategy. In ecosystems where hysteresis is counter-clockwise, rapid reduction in a driver variable from high to low levels may be 111 a successful restoration strategy. In contrast, systems that have experienced chronic low-levels of enrichment may exhibit 112 clockwise hysteresis that requires more extreme reductions of the driver variable, or alternative restoration strategies 36 , to 113 restore. abstract: Incremental increases in a driver variable, such as nutrients or detritus, can trigger abrupt shifts in aquatic ecosys-tems. Once these ecosystems change state, a simple reduction in the driver variable may not return them to their original state. Because of the long time scales involved, we still have a poor understanding of the dynamics of ecosys-tem recovery after a state change. A model system for understanding ecosystem recovery is the aquatic microecosystem that inhabits the cup-shaped leaves of the pitcher plant Sarracenia purpurea. With enrichment of organic matter, this system flips within 1 to 3 days from an oxygen-rich state to an oxygen-poor (hypoxic) state. In a replicated green-house experiment, we enriched pitcher plant leaves at different rates with bovine serum albumin (BSA), a molecular substitute for detritus. Changes in dissolved oxygen ([O2]) and undigested BSA concentration were monitored during enrichment and recovery phases. At low enrichment rates, ecosystems showed a substantial lag in the recovery of [O2] (clockwise hysteresis). At intermediate enrichment rates, [O2] tracked the levels of undigested BSA with the same profile during the enrichment and recovery phases (no hysteresis). At high enrichment rates, we observed a novel response: changes in [O2] were proportionally larger during the recovery phase than during the enrichment phase (counter-clockwise hysteresis). These experiments demonstrate that detrital enrichment rate can modulate a diversity of hysteretic responses in a single aquatic ecosystem. With counter-clockwise hysteresis, rapid reduction of a driver variable following high enrichment rates may be a viable restoration strategy. url: https://doi.org/10.1101/2020.05.01.073239 doi: 10.1101/2020.05.01.073239 id: cord-102725-k0xhbssu author: Norwood, Jordan N. title: Intranasal Administration of Functionalized Soot Particles Disrupts Olfactory Sensory Neuron Progenitor Cells in the Neuroepithelium date: 2020-08-19 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Exposure to air pollution has been linked to the development of neurodegenerative diseases and anosmia, but the underlying mechanism is not known. Additionally, the loss of olfactory function often precedes the onset of neurodegenerative diseases. Chemical ablation of olfactory sensory neurons blocks the drainage of cerebrospinal fluid (CSF) through the cribriform plate and alters normal CSF production and/or circulation. Damage to this drainage pathway could contribute to the development of neurodegenerative diseases and could link olfactory sensory neuron health and neurodegeneration. Here, we investigated the impact of intranasal treatment of combustion products (laboratory-generated soots) and their oxygen functionalized derivatives on mouse olfactory sensory neurons, olfactory nerve cell progenitors, and the behavior of the mouse. We found that after a month of every-other-day intranasal treatment of soots, there was minimal effect on olfactory sensory neuron anatomy or exploratory behavior in the mouse. However, oxygen-functionalized soot caused a large decrease in globose basal cells, which are olfactory progenitor cells. These results suggest that exposure to air pollution damages the olfactory neuron progenitor cells, and could lead to decreases in the number of olfactory neurons, potentially disrupting CSF drainage. url: https://doi.org/10.1101/2020.08.19.256297 doi: 10.1101/2020.08.19.256297 id: cord-103888-ggm29vrz author: Nova, Nicole title: Susceptible host availability modulates climate effects on dengue dynamics date: 2020-10-19 words: 1538.0 sentences: 86.0 pages: flesch: 44.0 cache: ./cache/cord-103888-ggm29vrz.txt txt: ./txt/cord-103888-ggm29vrz.txt summary: By analyzing incidence data, estimated susceptible population size, and climate data with methods based on nonlinear time series analysis (collectively referred to as empirical dynamic modeling), we identified drivers and their interactive effects on dengue dynamics in San Juan, Puerto Rico. By capturing mechanistic, nonlinear, and context-dependent effects of population susceptibility, temperature, and rainfall on dengue transmission empirically, our model improves forecast skill over recent, state-of-the-art models for dengue incidence. Scenario exploration with multivariate EDM allowed us to assess the effect of a 270 small change in temperature or rainfall on dengue incidence, across different states 271 of the system. Compared to 298 the other drivers, the converging cross-mapping skill of the temperature null 299 models were relatively high (Figures 3 and S8 As expected, EDM tests for putative causality in the nonsensical directions-304 incidence driving temperature or rainfall-were not significant (i.e., no convergence; Figure S7 , black lines). abstract: Experiments and models suggest that climate affects mosquito-borne disease transmission. However, disease transmission involves complex nonlinear interactions between climate and population dynamics, which makes detecting climate drivers at the population level challenging. By analyzing incidence data, estimated susceptible population size, and climate data with methods based on nonlinear time series analysis (collectively referred to as empirical dynamic modeling), we identified drivers and their interactive effects on dengue dynamics in San Juan, Puerto Rico. Climatic forcing arose only when susceptible availability was high: temperature and rainfall had net positive and negative effects, respectively. By capturing mechanistic, nonlinear, and context-dependent effects of population susceptibility, temperature, and rainfall on dengue transmission empirically, our model improves forecast skill over recent, state-of-the-art models for dengue incidence. Together, these results provide empirical evidence that the interdependence of host population susceptibility and climate drive dengue dynamics in a nonlinear and complex, yet predictable way. url: https://doi.org/10.1101/2019.12.20.883363 doi: 10.1101/2019.12.20.883363 id: cord-103563-7a3wdduq author: Nunez-Bajo, Estefania title: Ultra-Low-Cost Integrated Silicon-based Transducer for On-Site, Genetic Detection of Pathogens date: 2020-03-25 words: 4535.0 sentences: 211.0 pages: flesch: 44.0 cache: ./cache/cord-103563-7a3wdduq.txt txt: ./txt/cord-103563-7a3wdduq.txt summary: Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. abstract: Rapid screening and low-cost diagnosis play a crucial role in choosing the correct course of intervention e.g., drug therapy, quarantine, no action etc. when dealing with highly infectious pathogens. This is especially important if the disease-causing agent has no effective treatment, such as the novel coronavirus SARS-CoV-2 (the pathogen causing COVID-19), and shows no or similar symptoms to other common infections. We report a silicon-based integrated Point-of-Need (PoN) transducer (TriSilix) that can chemically-amplify and detect pathogen-specific sequences of nucleic acids (NA) quantitatively in real-time. Unlike other silicon-based technologies, TriSilix can be produced at wafer-scale in a standard laboratory; we have developed a series of methodologies based on metal-assisted chemical (wet) etching, electroplating, thermal bonding and laser-cutting to enable a cleanroom-free low-cost fabrication that does not require processing in an advanced semiconductor foundry. TriSilix is, therefore, resilient to disruptions in the global supply chain as the devices can be produced anywhere in the world. To create an ultra-low-cost device, the architecture proposed exploits the intrinsic properties of silicon and integrates three modes of operation in a single chip: i) electrical (Joule) heater, ii) temperature sensor (i.e. thermistor) with a negative temperature coefficient that can provide the precise temperature of the sample solution during reaction and iii) electrochemical sensor for detecting target NA. Using TriSilix, the sample solution can be maintained at a single, specific temperature (needed for isothermal amplification of NA such as Recombinase Polymerase Amplification (RPA) or cycled between different temperatures (with a precision of ±1.3°C) for Polymerase Chain Reaction (PCR) while the exact concentration of amplicons is measured quantitatively and in real-time electrochemically. A single 4-inch Si wafer yields 37 TriSilix chips of 10×10×0.65 mm in size and can be produced in 7 hours, costing ~US $0.35 per device. The system is operated digitally, portable and low power – capable of running up to 35 tests with a 4000 mAh battery (a typical battery capacity of a modern smartphone). We were able to quantitatively detect a 563-bp fragment (Insertion Sequence IS900) of the genomic DNA of M. avium subsp. paratuberculosis (extracted from cultured field samples) through PCR in real-time with a Limit-of-Detection of 20 fg, equivalent to a single bacterium, at the 30th cycle. Using TriSilix, we also detected the cDNA from SARS-CoV-2 (1 pg), through PCR, with high specificity against SARS-CoV (2003). url: https://doi.org/10.1101/2020.03.23.002931 doi: 10.1101/2020.03.23.002931 id: cord-291590-24psoaer author: Ogando, Natacha S. title: The enzymatic activity of the nsp14 exoribonuclease is critical for replication of Middle East respiratory syndrome-coronavirus date: 2020-06-20 words: 4299.0 sentences: 228.0 pages: flesch: 52.0 cache: ./cache/cord-291590-24psoaer.txt txt: ./txt/cord-291590-24psoaer.txt summary: In line with such a role, ExoN-knockout mutants of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) were previously found to have a crippled but viable hypermutation phenotype. Remarkably, using an identical reverse genetics approach, an extensive mutagenesis study revealed the corresponding ExoN-knockout mutants of another betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), to be non-viable. Our study thus reveals an additional function for MERS-CoV nsp14 ExoN, which apparently is critical for primary viral RNA synthesis, thus differentiating it from the proofreading activity thought to boost long-term replication fidelity in MHV and SARS-CoV. Strikingly, we now established that the equivalent knockout mutants of MERS-CoV ExoN are non-viable and completely deficient in RNA synthesis, thus revealing an additional and more critical function of ExoN in coronavirus replication. abstract: Coronaviruses (CoVs) stand out for their large RNA genome and complex RNA-synthesizing machinery comprising 16 nonstructural proteins (nsps). The bifunctional nsp14 contains an N-terminal 3’-to-5’ exoribonuclease (ExoN) and a C-terminal N7-methyltransferase (N7-MTase) domain. While the latter presumably operates during viral mRNA capping, ExoN is thought to mediate proofreading during genome replication. In line with such a role, ExoN-knockout mutants of mouse hepatitis virus (MHV) and severe acute respiratory syndrome coronavirus (SARS-CoV) were previously found to have a crippled but viable hypermutation phenotype. Remarkably, using an identical reverse genetics approach, an extensive mutagenesis study revealed the corresponding ExoN-knockout mutants of another betacoronavirus, Middle East respiratory syndrome coronavirus (MERS-CoV), to be non-viable. This is in agreement with observations previously made for alpha- and gammacoronaviruses. Only a single MERS-CoV ExoN active site mutant could be recovered, likely because the introduced D191E substitution is highly conservative in nature. For 11 other MERS-CoV ExoN active site mutants, not a trace of RNA synthesis could be detected, unless – in some cases – reversion had first occurred. Subsequently, we expressed and purified recombinant MERS-CoV nsp14 and established in vitro assays for both its ExoN and N7-MTase activities. All ExoN knockout mutations that were lethal when tested via reverse genetics were found to severely decrease ExoN activity, while not affecting N7-MTase activity. Our study thus reveals an additional function for MERS-CoV nsp14 ExoN, which apparently is critical for primary viral RNA synthesis, thus differentiating it from the proofreading activity thought to boost long-term replication fidelity in MHV and SARS-CoV. Importance The bifunctional nsp14 subunit of the coronavirus replicase contains 3’-to-5’ exoribonuclease (ExoN) and N7-methyltransferase (N7-MTase) domains. For the betacoronaviruses MHV and SARS-CoV, the ExoN domain was reported to promote the fidelity of genome replication, presumably by mediating some form of proofreading. For these viruses, ExoN knockout mutants are alive while displaying an increased mutation frequency. Strikingly, we now established that the equivalent knockout mutants of MERS-CoV ExoN are non-viable and completely deficient in RNA synthesis, thus revealing an additional and more critical function of ExoN in coronavirus replication. Both enzymatic activities of (recombinant) MERS-CoV nsp14 were evaluated using newly developed in vitro assays that can be used to characterize these key replicative enzymes in more detail and explore their potential as target for antiviral drug development. url: https://doi.org/10.1101/2020.06.19.162529 doi: 10.1101/2020.06.19.162529 id: cord-103770-4svaq0at author: Ogrodzinski, Martin P. title: Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes date: 2019-10-07 words: 668.0 sentences: 49.0 pages: flesch: 46.0 cache: ./cache/cord-103770-4svaq0at.txt txt: ./txt/cord-103770-4svaq0at.txt summary: title: Metabolomic profiling of mouse mammary tumor derived cell lines reveals targeted therapy options for cancer subtypes Here, we used tumor-derived cell lines derived from the MMTV-Myc mouse model to investigate metabolic pathways that are differentially utilized between two subtypes of breast cancer. To determine metabolic profiles of histologically distinct mouse mammary tumor subtypes, 84 polar metabolites were extracted from tumor-derived cell lines and quantitated using LC-MS/MS. We found metabolites involved in several central carbon metabolic pathways to be differentially 86 abundant between EMT and papillary tumor-derived cell lines (Figure 2 ). In the EMT subtype, both oxidized and reduced forms of glutathione, a key metabolite in 88 redox homeostasis, are elevated ( Figure 2B ). Metabolites 92 increased in the papillary subtype include fructose bisphosphate (FBP; glycolysis); acetyl-CoA indicating relative metabolite differences between EMT and papillary tumor derived cell lines. (B) Representative bar graphs of metabolites with statistically significant differences between EMT and papillary subtypes. abstract: Breast cancer is a heterogeneous disease with several subtypes that currently do not have targeted therapy options. Metabolomics has the potential to uncover novel targeted treatment strategies by identifying metabolic pathways required for cancer cells to survive and proliferate. Here, we used tumor-derived cell lines derived from the MMTV-Myc mouse model to investigate metabolic pathways that are differentially utilized between two subtypes of breast cancer. Using mass spectrometry-based metabolomics techniques, we identified differences in glycolysis, the tricarboxylic acid cycle, glutathione metabolism, and nucleotide metabolism between subtypes. We further show the feasibility of targeting these pathways in a subtype-specific manner using metabolism-targeting compounds. url: https://doi.org/10.1101/796573 doi: 10.1101/796573 id: cord-103174-4m3ajc8a author: Okada, Megan title: Doxycycline has Distinct Apicoplast-Specific Mechanisms of Antimalarial Activity date: 2020-10-16 words: 2809.0 sentences: 148.0 pages: flesch: 49.0 cache: ./cache/cord-103174-4m3ajc8a.txt txt: ./txt/cord-103174-4m3ajc8a.txt summary: Doxycycline (DOX) is a key antimalarial drug thought to kill Plasmodium parasites by blocking protein translation in the essential apicoplast organelle. Exogenous iron rescues parasites and apicoplast biogenesis from first-but not second-cycle effects of 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism distinct from the delayed-death mechanism. We observed that IPP shifted the 48-hour EC50 value of DOX from 5 ± 1 to 12 ± 2 µM 100 (average ± SD of 5 independent assays, P = 0.001 by unpaired t-test) ( Figure 2C and Figure 2 -101 figure supplement 1), suggesting that first-cycle growth defects from 5-10 µM DOX reflect an 102 apicoplast-specific mechanism but that DOX concentrations >10 µM cause off-target defects 103 outside this organelle. abstract: Doxycycline (DOX) is a key antimalarial drug thought to kill Plasmodium parasites by blocking protein translation in the essential apicoplast organelle. Clinical use is primarily limited to prophylaxis due to delayed second-cycle parasite death at 1-3 μM serum concentrations. DOX concentrations >5 μM kill parasites with first-cycle activity but have been ascribed to off-target mechanisms outside the apicoplast. We report that 10 μM DOX blocks apicoplast biogenesis in the first cycle and is rescued by isopentenyl pyrophosphate, an essential apicoplast product, confirming an apicoplast-specific mechanism. Exogenous iron rescues parasites and apicoplast biogenesis from first-but not second-cycle effects of 10 μM DOX, revealing that first-cycle activity involves a metal-dependent mechanism distinct from the delayed-death mechanism. These results critically expand the paradigm for understanding the fundamental antiparasitic mechanisms of DOX and suggest repurposing DOX as a faster-acting antimalarial at higher dosing whose multiple mechanisms would be expected to limit parasite resistance. url: https://doi.org/10.1101/2020.06.11.146407 doi: 10.1101/2020.06.11.146407 id: cord-322942-y4zd2oui author: Olagnier, David title: Identification of SARS-CoV2-mediated suppression of NRF2 signaling reveals a potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate date: 2020-07-17 words: 3756.0 sentences: 203.0 pages: flesch: 50.0 cache: ./cache/cord-322942-y4zd2oui.txt txt: ./txt/cord-322942-y4zd2oui.txt summary: Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. Here we demonstrate that expression of NRF2-dependent genes is suppressed in biopsies from 104 COVID-19 patients and that treatment of cells with NRF2 agonists 4-OI and DMF induces a 105 strong anti-viral program that limits SARS-CoV2 replication. Interestingly, when 176 treating Calu3 cells with DMF, another known NRF2 inducer and a clinically approved drug in 177 the first-line-of treatment of multiple sclerosis, we could also observe an anti-viral effect toward 178 SARS-CoV2 replication similar in magnitude as what we had observed with 4-OI (Fig 2p-q) as 179 well as a reduced but significant effect when using Vero cells (Fig. 2r) . abstract: Antiviral strategies to inhibit Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) and the pathogenic consequences of COVID-19 are urgently required. Here we demonstrate that the NRF2 anti-oxidant gene expression pathway is suppressed in biopsies obtained from COVID-19 patients. Further, we uncover that NRF2 agonists 4-octyl-itaconate (4-OI) and the clinically approved dimethyl fumarate (DMF) induce a cellular anti-viral program, which potently inhibits replication of SARS-CoV2 across cell lines. The anti-viral program extended to inhibit the replication of several other pathogenic viruses including Herpes Simplex Virus-1 and-2, Vaccinia virus, and Zika virus through a type I interferon (IFN)-independent mechanism. In addition, induction of NRF2 by 4-OI and DMF limited host inflammatory responses to SARS-CoV2 infection associated with airway COVID-19 pathology. In conclusion, NRF2 agonists 4-OI and DMF induce a distinct IFN-independent antiviral program that is broadly effective in limiting virus replication and suppressing the pro-inflammatory responses of human pathogenic viruses, including SARS-CoV2. One Sentence Summary NRF2 agonists 4-octyl-itaconate (4-OI) and dimethyl fumarate inhibited SARS-CoV2 replication and virus-induced inflammatory responses, as well as replication of other human pathogenic viruses. url: https://doi.org/10.1101/2020.07.16.206458 doi: 10.1101/2020.07.16.206458 id: cord-280198-bhjw6xc5 author: Olaleye, Omonike A. title: Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 - Spike Protein Interaction In Vitro date: 2020-08-14 words: 1814.0 sentences: 112.0 pages: flesch: 49.0 cache: ./cache/cord-280198-bhjw6xc5.txt txt: ./txt/cord-280198-bhjw6xc5.txt summary: title: Discovery of Clioquinol and Analogues as Novel Inhibitors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection, ACE2 and ACE2 Spike Protein Interaction In Vitro Here in, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a FDA approved drug and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection induced cytopathic effect in vitro. In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. Therefore, targeting 106 the interaction between human ACE2 receptor and the RBD in S protein of SARS-CoV-2 could 107 serve as a promising approach for the development of effective entry inhibitors for potential 108 prevention and/or treatment of COVID-19. Activity of Clioquinol (CLQ) and Analogues against ACE2 Exopeptidase Activity and 725 ACE2 and SARS-CoV-2 Spike (RBD) Protein Interaction abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the etiological agent for coronavirus disease 2019 (COVID-19), has emerged as an ongoing global pandemic. Presently, there are no clinically approved vaccines nor drugs for COVID-19. Hence, there is an urgent need to accelerate the development of effective antivirals. Here in, we discovered Clioquinol (5-chloro-7-iodo-8-quinolinol (CLQ)), a FDA approved drug and two of its analogues (7-bromo-5-chloro-8-hydroxyquinoline (CLBQ14); and 5, 7-Dichloro-8-hydroxyquinoline (CLCQ)) as potent inhibitors of SARS-CoV-2 infection induced cytopathic effect in vitro. In addition, all three compounds showed potent anti-exopeptidase activity against recombinant human angiotensin converting enzyme 2 (rhACE2) and inhibited the binding of rhACE2 with SARS-CoV-2 Spike (RBD) protein. CLQ displayed the highest potency in the low micromolar range, with its antiviral activity showing strong correlation with inhibition of rhACE2 and rhACE2-RBD interaction. Altogether, our findings provide a new mode of action and molecular target for CLQ and validates this pharmacophore as a promising lead series for clinical development of potential therapeutics for COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32817951/ doi: 10.1101/2020.08.14.250480 id: cord-255997-oer5lxxr author: Onodi, Fanny title: SARS-CoV-2 induces activation and diversification of human plasmacytoid pre-dendritic cells date: 2020-07-10 words: 4209.0 sentences: 254.0 pages: flesch: 53.0 cache: ./cache/cord-255997-oer5lxxr.txt txt: ./txt/cord-255997-oer5lxxr.txt summary: Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Interestingly, pDC responded to SARS-CoV-2 by a complete activation program, including diversification into effector subsets, production of type I and type III IFN, as well as inflammatory cytokines. We also showed that hydroxychloroquine, an antimalarial drug proposed for treatment of COVID-19 patients (Das et al., 2020; Mahévas et al., 2020) , inhibits SARS-CoV-2-induced pDC activation and IFN production in a dose-dependent manner. Following 24 hours of culture, we found that HCQ inhibited pDC diversification in response to SARS-CoV-2, which is similar to the decrease observed with Flu, used as a positive control ( Fig 4A) . abstract: Several studies have analyzed antiviral immune pathways in severe COVID-19 patients. However, the initial steps of antiviral immunity are not known. Here, we have studied the interaction of isolated primary SARS-CoV-2 viral strains with human plasmacytoid pre-dendritic cells (pDC), a key player in antiviral immunity. We show that pDC are not permissive to SARS-CoV-2 infection. However, they efficiently diversified into activated P1-, P2-, and P3-pDC effector subsets in response to viral stimulation. They expressed checkpoint molecules at levels similar to influenza virus-induced activation. They rapidly produced high levels of interferon-α, interferon-λ1, IL-6, IP-10, and IL-8. Importantly, all major aspects of SARS-CoV-2-induced pDC activation were inhibited by hydroxychloroquine, including P2- and P3-pDC differentiation, the expression of maturation markers, and the production of interferon-α and inflammatory cytokines. Our results indicate that pDC may represent a major player in the first line of defense against SARS-CoV-2 infection, and call for caution in the use of hydroxychloroquine in the early treatment of the disease. url: https://doi.org/10.1101/2020.07.10.197343 doi: 10.1101/2020.07.10.197343 id: cord-262119-s6hc7fxs author: Ostaszewski, Marek title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms date: 2020-10-27 words: 12332.0 sentences: 742.0 pages: flesch: 38.0 cache: ./cache/cord-262119-s6hc7fxs.txt txt: ./txt/cord-262119-s6hc7fxs.txt summary: title: COVID-19 Disease Map, a computational knowledge repository of SARS-CoV-2 virus-host interaction mechanisms The molecular pathophysiology that links SARS-CoV-2 infection to the clinical manifestations and course of COVID-19 is complex and spans multiple biological pathways, cell types and organs [2, 3] . With this goal in mind, we initiated a collaborative effort involving over 230 biocurators, domain experts, modelers and data analysts from 120 institutions in 30 countries to develop the COVID-19 Disease Map, an open-access collection of curated computational diagrams and models of molecular mechanisms implicated in the disease [4] . The COVID-19 Disease Map diagrams, available in layout-aware systems biology formats and integrated with external repositories, are available in several formats allowing a range of computational analyses, including network analysis and Boolean, kinetic or multiscale simulations. COVID-19 Disease Map, building a computational repository of SARS-CoV-2 virus-host interaction mechanisms abstract: We hereby describe a large-scale community effort to build an open-access, interoperable, and computable repository of COVID-19 molecular mechanisms - the COVID-19 Disease Map. We discuss the tools, platforms, and guidelines necessary for the distributed development of its contents by a multi-faceted community of biocurators, domain experts, bioinformaticians, and computational biologists. We highlight the role of relevant databases and text mining approaches in enrichment and validation of the curated mechanisms. We describe the contents of the map and their relevance to the molecular pathophysiology of COVID-19 and the analytical and computational modelling approaches that can be applied to the contents of the COVID-19 Disease Map for mechanistic data interpretation and predictions. We conclude by demonstrating concrete applications of our work through several use cases. url: https://doi.org/10.1101/2020.10.26.356014 doi: 10.1101/2020.10.26.356014 id: cord-342015-bz2vab6e author: Ouadfeul, Sid-Ali title: Multifractal Analysis of SARS-CoV-2 Coronavirus genomes using the wavelet transform date: 2020-08-16 words: 1386.0 sentences: 86.0 pages: flesch: 58.0 cache: ./cache/cord-342015-bz2vab6e.txt txt: ./txt/cord-342015-bz2vab6e.txt summary: In this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Arneodo et al (1996) published a paper deals with the study of the Long-Range Correlation (LRC) character of DNA sequences using the 1D continuous wavelet transform method. Audit et al (2004) published a paper deals with wavelet Analysis of DNA bending profiles reveals structural constraints on the evolution of genomic sequences, Voss (1996) published a paper deals with the evolution of Long-Range fractal correlations and 1/f noise in DNA base sequences. In this paper the 1D Wavelet Transform Modulus Maxima Lines (WTMM) method is used to demonstrate the monofractal behavior of SARS-CoV-2 RNA sequences downloaded from the NCBI database and to estimate the so-called Hurst exponent, the goal is to investigate the LRC character in these sequences. abstract: In this paper, the 1D Wavelet Transform Modulus Maxima lines (WTMM) method is used to investigate the Long-Range Correlation (LRC) and to estimate the so-called Hurst exponent of 21 isolate RNA sequence downloaded from the NCBI database of patients infected by SARS-CoV-2, Coronavirus, the Knucleotidic, Purine, Pyramidine, Ameno, Keto and GC DNA coding are used. Obtained results show the LRC character in the most sequences; except some sequences where the anti-correlated or the Classical Brownian motion character is observed. Obtained results demonstrate show that the SARS-Cov2 coronavirus undergoes mutation from a country to another or in the same country. url: https://doi.org/10.1101/2020.08.15.252411 doi: 10.1101/2020.08.15.252411 id: cord-277648-9kxwkcbl author: Overholt, Kalon J. title: Dissecting the common and compartment-specific features of COVID-19 severity in the lung and periphery with single-cell resolution date: 2020-06-19 words: 10003.0 sentences: 421.0 pages: flesch: 39.0 cache: ./cache/cord-277648-9kxwkcbl.txt txt: ./txt/cord-277648-9kxwkcbl.txt summary: Bulk RNA sequencing (bulk RNA-seq) and single-cell RNA sequencing (scRNA-seq) studies have identified stark transcriptional differences between bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cell (PBMC) samples in hospitalized COVID-19 patients, indicating that immunological responses may be highly compartment-specific [21, 22] . We used identical methods to separately analyze multi-donor scRNA-seq datasets from bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMCs) in COVID-19 patients classified by severity strata as well as healthy control subjects to investigate severity-specific immune dysregulation in the lung and periphery. When we increased this analysis to include all of the cell types found in the BALF (Figure 3A We next investigated pathway-level changes occurring in PBMCs and found that differential gene expression between ARDS and non-ARDS patients supported the detection of statistically enriched pathways through GSEA. abstract: As the global COVID-19 pandemic continues to escalate, no effective treatment has yet been developed for the severe respiratory complications of this disease. This may be due in large part to the unclear immunopathological basis for the development of immune dysregulation and acute respiratory distress syndrome (ARDS) in severe and critical patients. Specifically, it remains unknown whether the immunological features of the disease that have been identified so far are compartment-specific responses or general features of COVID-19. Additionally, readily detectable biological markers correlated with strata of disease severity that could be used to triage patients and inform treatment options have not yet been identified. Here, we leveraged publicly available single-cell RNA sequencing data to elucidate the common and compartment-specific immunological features of clinically severe COVID-19. We identified a number of transcriptional programs that are altered across the spectrum of disease severity, few of which are common between the lung and peripheral immune environments. In the lung, comparing severe and moderate patients revealed severity-specific responses of enhanced interferon, A20/IκB, IL-2, and IL-6 pathway signatures along with broad signaling activity of IFNG, SPP1, CCL3, CCL8, and IL18 across cell types. These signatures contrasted with features unique to ARDS observed in the blood compartment, which included depletion of interferon and A20/IκB signatures and a lack of IL-6 response. The cell surface marker S1PR1 was strongly upregulated in patients diagnosed with ARDS compared to non-ARDS patients in γδ T cells of the blood compartment, and we nominate S1PR1 as a potential marker for immunophenotyping ARDS in COVID-19 patients using flow cytometry. HIGHLIGHTS COVID-19 disease severity is associated with a number of compositional shifts in the cellular makeup of the blood and lung environments. Transcriptional data suggest differentially expressed cell surface proteins as markers for COVID-19 immunophenotyping from BALF and PBMC samples. Severity-specific features COVID-19 manifest at the pathway level, suggesting distinct changes to epithelia and differences between local and systemic immune dynamics. Immune-epithelial cellular communication analysis identifies ligands implicated in transcriptional regulation of proto-oncogenes in the lung epithelia of severe COVID-19 patients. Network analysis suggests broadly-acting dysregulatory ligands in the pulmonary microenvironment as candidate therapeutic targets for the treatment of severe COVID-19. url: https://doi.org/10.1101/2020.06.15.147470 doi: 10.1101/2020.06.15.147470 id: cord-339772-q814d6l7 author: Pach, Szymon title: ACE2-Variants Indicate Potential SARS-CoV-2-Susceptibility in Animals: An Extensive Molecular Dynamics Study date: 2020-05-14 words: 3735.0 sentences: 229.0 pages: flesch: 60.0 cache: ./cache/cord-339772-q814d6l7.txt txt: ./txt/cord-339772-q814d6l7.txt summary: To investigate the reason for the variable susceptibility observed in different species, we have developed molecular descriptors to efficiently analyze our dynamic simulation models of complexes between SARS-CoV-2 S and ACE2. Moreover, we compared ACE2 sequences from rodents (mouse, rat, hamster, and red squirrel) to sample additional binding pockets in the ACE2-RBD interface and predict susceptibility to SARS-CoV-2 of the red squirrel (Sciurus vulgaris). To compare three-dimensional binding interfaces of animal ACE2-RBD complexes, we developed homology models of dog, cat, ferret, hamster, mouse, rat, and red squirrel proteins. Both outlier residues are located on flexible loops of ACE2 distal to the S binding site and represent polymorphic mutations from glycine in human crystal structure to serine in homology models. Based on known susceptibility of animal species to SARS-CoV-2 and the comparison of MD trajectories, we were able to develop models for prediction of RBD binding to ACE2. abstract: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in late 2019 and since evolved into a global threat with nearly 4.4 million infected people and over 290,000 confirmed deaths worldwide.1 SARS-CoV-2 is an enveloped virus presenting spike (S) glycoproteins on its outer surface. Binding of S to host cell angiotensin converting enzyme 2 (ACE2) is thought to be critical for cellular entry. The host range of the virus extends far beyond humans and non-human primates. Natural and experimental infections have confirmed high susceptibility of cats, ferrets, and hamsters, whereas dogs, mice, rats, pigs, and chickens seem refractory to SARS-CoV-2 infection. To investigate the reason for the variable susceptibility observed in different species, we have developed molecular descriptors to efficiently analyze our dynamic simulation models of complexes between SARS-CoV-2 S and ACE2. Based on our analyses we predict that: (i) the red squirrel is likely susceptible to SARS-CoV-2 infection and (ii) specific mutations in ACE2 of dogs, rats, and mice render them susceptible to SARS-CoV-2 infection. url: https://doi.org/10.1101/2020.05.14.092767 doi: 10.1101/2020.05.14.092767 id: cord-273083-xrydkiu4 author: Pahmeier, Felix title: A versatile reporter system to monitor virus infected cells and its application to dengue virus and SARS-CoV-2 date: 2020-09-01 words: 999.0 sentences: 64.0 pages: flesch: 49.0 cache: ./cache/cord-273083-xrydkiu4.txt txt: ./txt/cord-273083-xrydkiu4.txt summary: Here, we describe the generation and characterization of a reporter system to visualize dengue virus and SARS-CoV-2 replication in live cells. The system is based on viral protease activity causing cleavage and nuclear translocation of an engineered fluorescent protein that is expressed in the infected cells. Here we describe a reporter system that takes advantage of virus-encoded proteases that are expressed in infected cells to cleave an ER-anchored fluorescent protein fused to a nuclear localization sequence. Using this system, we demonstrate reliable reporting activity for two major human pathogens from the Flaviviridae and the Coronaviridae families: dengue virus and SARS-CoV-2. In order to generate a reporter system that can specifically indicate virus infection, we 219 designed a construct expressing a GFP fusion protein that could selectively be cleaved 220 by viral proteases. However, since no fluorescent 304 protein coding sequence is incorporated into the construct, expression of the DENV 305 polyprotein cannot be followed by live cell imaging. abstract: Positive-strand RNA viruses have been the etiological agents in several major disease outbreaks over the last few decades. Examples of that are flaviviruses, such as dengue virus and Zika virus that cause millions of yearly infections and spread around the globe, and coronaviruses, such as SARS-CoV-2, which is the cause of the current pandemic. The severity of outbreaks caused by these viruses stresses the importance of virology research in determining mechanisms to limit virus spread and to curb disease severity. Such studies require molecular tools to decipher virus-host interactions and to develop effective interventions. Here, we describe the generation and characterization of a reporter system to visualize dengue virus and SARS-CoV-2 replication in live cells. The system is based on viral protease activity causing cleavage and nuclear translocation of an engineered fluorescent protein that is expressed in the infected cells. We show the suitability of the system for live cell imaging and visualization of single infected cells as well as for screening and testing of antiviral compounds. Given the modular building blocks, the system is easy to manipulate and can be adapted to any virus encoding a protease, thus offering a high degree of flexibility. IMPORTANCE Reporter systems are useful tools for fast and quantitative visualization of viral replication and spread within a host cell population. Here we describe a reporter system that takes advantage of virus-encoded proteases that are expressed in infected cells to cleave an ER-anchored fluorescent protein fused to a nuclear localization sequence. Upon cleavage, the fluorescent protein translocates to the nucleus, allowing for rapid detection of the infected cells. Using this system, we demonstrate reliable reporting activity for two major human pathogens from the Flaviviridae and the Coronaviridae families: dengue virus and SARS-CoV-2. We apply this reporter system to live cell imaging and use it for proof-of-concept to validate antiviral activity of a nucleoside analogue. This reporter system is not only an invaluable tool for the characterization of viral replication, but also for the discovery and development of antivirals that are urgently needed to halt the spread of these viruses. url: https://doi.org/10.1101/2020.08.31.276683 doi: 10.1101/2020.08.31.276683 id: cord-254772-1xzkfl8g author: Pandolfi, Laura title: Neutrophil extracellular traps induce the epithelial-mesenchymal transition: implications in post-COVID-19 fibrosis date: 2020-11-09 words: 4248.0 sentences: 252.0 pages: flesch: 55.0 cache: ./cache/cord-254772-1xzkfl8g.txt txt: ./txt/cord-254772-1xzkfl8g.txt summary: Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1β, best-known inducers of NETosis. Because of the high levels of NETs in the BAL of COVID-19 patients and their potential role in inducing the EMT, we next focused on the correlation between NETs and the EMT by setting up an in vitro alveolar model that we infected with SARS-CoV-2. In particular, we would like to propose a model in which macrophages, by releasing IL8 and IL1β, two cytokines significantly increased in the plasma (32, 33) and BAL-fluid of severe COVID-19 patients (14), potentiate the capacity of NETs released by Neu to amplify the noxious activity on lung cells, favoring the EMT. abstract: The release of neutrophil extracellular traps (NETs), a process termed NETosis, avoids pathogen spread but may cause tissue injury. NETs have been found in severe COVID-19 patients, but their role in disease development is still unknown. The aim of this study is to assess the capacity of NETs to drive epithelial-mesenchymal transition (EMT) of lung epithelial cells and to analyze the involvement of NETs in COVID-19. Neutrophils activated with PMA (PMA-Neu), a stimulus known to induce NETs formation, induce both EMT and cell death in the lung epithelial cell line, A549. Notably, NETs isolated from PMA-Neu induce EMT without cell damage. Bronchoalveolar lavage fluid of severe COVID-19 patients showed high concentration of NETs. Thus, we tested in an in vitro alveolar model the hypothesis that virus-induced NET may drive EMT. Co-culturing A549 at air-liquid interface with alveolar macrophages, neutrophils and SARS-CoV2, we demonstrated a significant induction of the EMT in A549 together with high concentration of NETs, IL8 and IL1β, best-known inducers of NETosis. Lung tissues of COVID-19 deceased patients showed that epithelial cells are characterized by increased mesenchymal markers. These results show for the first time that NETosis plays a major role in triggering lung fibrosis in COVID-19 patients. url: https://doi.org/10.1101/2020.11.09.374769 doi: 10.1101/2020.11.09.374769 id: cord-284045-scd3f8vk author: Pape, Constantin title: Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera date: 2020-10-07 words: 5627.0 sentences: 300.0 pages: flesch: 53.0 cache: ./cache/cord-284045-scd3f8vk.txt txt: ./txt/cord-284045-scd3f8vk.txt summary: Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in specific, sensitive and unbiased assay which complements the portfolio of SARS-CoV-2 serological assays. The dsRNA co-localizing pattern 213 observed for sera from the negative control cohort is by definition non-specific for SARS-CoV-2, 214 but would be classified as a positive hit based on staining intensity alone. The high information content of the IF data (differential staining patterns) 363 together with a machine learning-based approach [45] and the implementation of stable cell lines 364 expressing selected viral antigens in the IF assay will provide additional parameters for 365 classification of patient sera and further improve sensitivity and specificity of the presented IF 366 assay. abstract: Emergence of the novel pathogenic coronavirus SARS-CoV-2 and its rapid pandemic spread presents numerous questions and challenges that demand immediate attention. Among these is the urgent need for a better understanding of humoral immune response against the virus as a basis for developing public health strategies to control viral spread. For this, sensitive, specific and quantitative serological assays are required. Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in specific, sensitive and unbiased assay which complements the portfolio of SARS-CoV-2 serological assays. The procedure described here has been used for clinical studies and provides a general framework for the application of quantitative high-throughput microscopy to rapidly develop serological assays for emerging virus infections. url: https://doi.org/10.1101/2020.06.15.152587 doi: 10.1101/2020.06.15.152587 id: cord-309411-2dfiwo65 author: Paris, Kristina A. title: Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology date: 2020-06-23 words: 4728.0 sentences: 256.0 pages: flesch: 58.0 cache: ./cache/cord-309411-2dfiwo65.txt txt: ./txt/cord-309411-2dfiwo65.txt summary: On the other hand, the loss of this pH-switch, which sequence alignments show is unique to CoV2, eliminates the transition state and allows the virus to stay bound to the ACE2 receptor for time scales compatible with the recruitment of additional ACE2 receptors diffusing in the cell membrane. Work on SARS-CoV (CoV1) has already determined that the virus enters cells via receptormediated endocytosis in a pH-dependent manner (Wang et al., 2008) that is characterized by cotranslocation of the viral spike glycoprotein and its specific functional receptor, the angiotensinconverting enzyme 2 (ACE2), from the cell surface to early endosomes. This newly discovered difference in protein sequence in the receptor binding domain of the spike glycoprotein and its impact on receptor binding reveals a mechanism that allows SARS-CoV2 internalization to take advantage of the high expression of ACE2 in the nasal epithelium¾resulting in increased retention times in the upper respiratory tract and augmented infectivity. abstract: Cell surface receptor engagement is a critical aspect of viral infection. This paper compares the dynamics of virus-receptor interactions for SARS-CoV (CoV1) and CoV2. At low (endosomal) pH, the binding free energy landscape of CoV1 and CoV2 interactions with the angiotensin-converting enzyme 2 (ACE2) receptor is almost the same. However, at neutral pH the landscape is different due to the loss of a pH-switch (His445Lys) in the receptor binding domain (RBD) of CoV2 relative to CoV1. Namely, CoV1 stabilizes a transition state above the bound state. In situations where small external strains are applied by, say, shear flow in the respiratory system, the off rate of the viral particle is enhanced. As a result, CoV1 virions are expected to detach from cell surfaces in time scales that are much faster than the time needed for other receptors to reach out and stabilize virus attachment. On the other hand, the loss of this pH-switch, which sequence alignments show is unique to CoV2, eliminates the transition state and allows the virus to stay bound to the ACE2 receptor for time scales compatible with the recruitment of additional ACE2 receptors diffusing in the cell membrane. This has important implications for viral infection and its pathology. CoV1 does not trigger high infectivity in the nasal area because it either rapidly drifts down the respiratory tract or is exhaled. By contrast, this novel mutation in CoV2 should not only retain the infection in the nasal cavity until ACE2-rich cells are sufficiently depleted, but also require fewer particles for infection. This mechanism explains observed longer incubation times, extended period of viral shedding, and higher rate of transmission. These considerations governing viral entry suggest that number of ACE2-rich cells in human nasal mucosa, which should be significantly smaller for children (and females relative to males), should also correlate with onset of viral load that could be a determinant of higher virus susceptibility. Critical implications for the development of new vaccines to combat current and future pandemics that, like SARS-CoV2, export evolutionarily successful strains via higher transmission rates by viral retention in nasal epithelium are also discussed. url: https://doi.org/10.1101/2020.06.16.155457 doi: 10.1101/2020.06.16.155457 id: cord-318253-vp22xd8p author: Parisi, Ortensia Ilaria title: “Monoclonal-type” plastic antibodies for SARS-CoV-2 based on Molecularly Imprinted Polymers date: 2020-05-28 words: 1858.0 sentences: 96.0 pages: flesch: 38.0 cache: ./cache/cord-318253-vp22xd8p.txt txt: ./txt/cord-318253-vp22xd8p.txt summary: Our idea is focused on the development of "monoclonal-type" plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. In this context, our idea is to develop "monoclonal-type" plastic antibodies based on Molecularly Imprinted Polymers (MIPs) for the selective recognition and binding of the RBD of the novel coronavirus SARS-CoV-2 in the aim to block the function of its spike protein (Figure 1.) . abstract: Our idea is focused on the development of “monoclonal-type” plastic antibodies based on Molecularly Imprinted Polymers (MIPs) able to selectively bind a portion of the novel coronavirus SARS-CoV-2 spike protein to block its function and, thus, the infection process. Molecular Imprinting, indeed, represents a very promising and attractive technology for the synthesis of MIPs characterized by specific recognition abilities for a target molecule. Given these characteristics, MIPs can be considered tailor-made synthetic antibodies obtained by a templating process. In the present study, the developed imprinted polymeric nanoparticles were characterized in terms of particles size and distribution by Dynamic Light Scattering (DLS) and the imprinting effect and selectivity were investigated by performing binding experiments using the receptor-binding domain (RBD) of the novel coronavirus and the RBD of SARS-CoV spike protein, respectively. Finally, the hemocompatibility of the prepared MIP-based plastic antibodies was also evaluated. url: https://doi.org/10.1101/2020.05.28.120709 doi: 10.1101/2020.05.28.120709 id: cord-347441-8ow952d8 author: Parvez, Md Sorwer Alam title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism date: 2020-06-07 words: 1027.0 sentences: 75.0 pages: flesch: 62.0 cache: ./cache/cord-347441-8ow952d8.txt txt: ./txt/cord-347441-8ow952d8.txt summary: title: Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh. As many of the Bangladeshi people return during the COVID-19 39 outbreak mainly from China, India, Saudi Arabia, Spain, Italy, Japan, Qatar, Canada, Kuwait, USA, 40 France, Sweden, and Switzerland, the first deposited genome sequence of those countries were also 41 retrieved. In total, three models were generated using the template PDB ID: 6VSB; one model for the spike protein 118 of reference strain, and the two others were for two different mutant isolates from Bangladesh (Fig 3) . abstract: As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh. url: https://doi.org/10.1101/2020.06.07.138800 doi: 10.1101/2020.06.07.138800 id: cord-339665-nwwutduy author: Patel, Ami title: Intradermal-delivered DNA vaccine provides anamnestic protection in a rhesus macaque SARS-CoV-2 challenge model date: 2020-07-29 words: 5258.0 sentences: 286.0 pages: flesch: 52.0 cache: ./cache/cord-339665-nwwutduy.txt txt: ./txt/cord-339665-nwwutduy.txt summary: Prior work with the related coronaviruses, SARS-CoV and MERS-CoV, delineated that the Spike protein of these viruses was an important target for development of neutralizing antibodies, and in animal viral challenges vaccine targeted immunity (reviewed in (Du et al., 2009; Roper and Rehm, 2009; Thanh Le et al., 2020) (Liu et al., 2018; Muthumani et al., 2015; van Doremalen et al., 2020a) . These memory titers were comparable to those observed in other reported protection studies in macaques performed at the acute phase of the vaccine-induced immune response (Gao et al., 2020; van Doremalen et al., 2020b; Yu et al., 2020) and those reported in the sera of convalescent patients (Ni et al., 2020; Robbiani et al., 2020) . Our study and other published reports show that DNA vaccination with candidates targeting the full-length SARS-CoV-2 spike protein likely increase the availability of T cell immunodominant epitopes leading to a broader and more potent immune response, compared to partial domains and truncated immunogens. abstract: Coronavirus disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, has had a dramatic global impact on public health, social, and economic infrastructures. Here, we assess immunogenicity and anamnestic protective efficacy in rhesus macaques of the intradermal (ID)-delivered SARS-CoV-2 spike DNA vaccine, INO-4800. INO-4800 is an ID-delivered DNA vaccine currently being evaluated in clinical trials. Vaccination with INO-4800 induced T cell responses and neutralizing antibody responses against both the D614 and G614 SARS-CoV-2 spike proteins. Several months after vaccination, animals were challenged with SARS-CoV-2 resulting in rapid recall of anti-SARS-CoV-2 spike protein T and B cell responses. These responses were associated with lower viral loads in the lung and with faster nasal clearance of virus. These studies support the immune impact of INO-4800 for inducing both humoral and cellular arms of the adaptive immune system which are likely important for providing durable protection against COVID-19 disease. url: https://doi.org/10.1101/2020.07.28.225649 doi: 10.1101/2020.07.28.225649 id: cord-102976-cic1gxrk author: Patel, Roosheel S. title: Single cell resolution landscape of equine peripheral blood mononuclear cells reveals diverse immune cell subtypes including T-bet+ B cells date: 2020-05-07 words: 7155.0 sentences: 378.0 pages: flesch: 45.0 cache: ./cache/cord-102976-cic1gxrk.txt txt: ./txt/cord-102976-cic1gxrk.txt summary: Single cell RNA-Sequencing (scRNA-Seq) offers an alternative to flow cytometry as it defines different cell types (and their functional states) by gene expression patterns rather than surface marker expression. To characterize equine PBMC at high resolution and establish a corresponding peripheral blood immune cell atlas, we independently analyzed scRNA-Seq data for the constituent clusters of each major cell group, except Basophils due to the low number of cells. Additional genes with significantly elevated expression levels in cluster 28 include NR4A1 (transcription factor necessary for differentiation of non-classical monocytes in mice) (23) , CX3CR1 (chemokine receptor characteristic of nonclassical monocytes in humans and mice) (24, 25) , and HES4 (target of NOTCH signaling implicated in non-classical monocyte generation) (26) (Fig. 2E ). To further support our cell type annotations and assess potential differences in monocyte/DC subsets between horses and humans, we performed cross-species hierarchical clustering with a human PBMC public reference scRNA-Seq data set ( Fig. S2A-B, Fig. 2G ). abstract: Traditional laboratory model organisms represent a small fraction of the diversity of multicellular life, and findings in any given experimental model often do not translate to other species. Immunology research in non-traditional model organisms can be advantageous or even necessary (e.g. for host-pathogen interaction studies), but presents multiple challenges, many stemming from an incomplete understanding of potentially species-specific immune cell types, frequencies and phenotypes. Identifying and characterizing immune cells in such organisms is frequently limited by the availability of species-reactive immunophenotyping reagents for flow cytometry, and insufficient prior knowledge of cell type-defining markers. Here, we demonstrate the utility of single cell RNA sequencing (scRNA-Seq) to characterize immune cells for which traditional experimental tools are limited. Specifically, we used scRNA-Seq to comprehensively define the cellular diversity of equine peripheral blood mononuclear cells (PBMCs) from healthy horses across different breeds, ages, and sexes. We identified 30 cell type clusters partitioned into five major populations: Monocytes/Dendritic Cells, B cells, CD3+PRF1+ lymphocytes, CD3+PRF1- lymphocytes, and Basophils. Comparative analyses revealed many cell populations analogous to human PBMC, including transcriptionally heterogeneous monocytes and distinct dendritic cell subsets (cDC1, cDC2, plasmacytoid DC). Unexpectedly, we found that a majority of the equine peripheral B cell compartment is comprised of T-bet+ B cells; an immune cell subpopulation typically associated with chronic infection and inflammation in human and mouse. Taken together, our results demonstrate the potential of scRNA-Seq for cellular analyses in non-traditional model organisms, and form the basis for an immune cell atlas of horse peripheral blood. url: https://doi.org/10.1101/2020.05.05.077362 doi: 10.1101/2020.05.05.077362 id: cord-259246-azt5sr9w author: Peng, Qi title: Structural basis of SARS-CoV-2 polymerase inhibition by Favipiravir date: 2020-10-19 words: 3216.0 sentences: 158.0 pages: flesch: 50.0 cache: ./cache/cord-259246-azt5sr9w.txt txt: ./txt/cord-259246-azt5sr9w.txt summary: This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. Recently, we and other groups have determined the structures of SARS-CoV-2 core polymerase complex in both apo and RNA-bound states 26-30 , providing important information for structure-based antiviral drug design. Similar observations were also reported recently that SARS-CoV-2 polymerase is more tolerant for mismatches between template and product residues than other viral RdRps 5 , which further highlights the requirement for the proofreading nuclease nsp14 to maintain the integrity of viral genome. Interestingly, Favipiravir could be incorporated into the RNA product with similar efficiencies to those of ATP or GTP substrates guided by U or C template residues, respectively (Fig. 1c) . abstract: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has developed into an unprecedented global pandemic. Nucleoside analogues, such as Remdesivir and Favipiravir, can serve as the first-line broad-spectrum antiviral drugs against the newly emerging viral diseases. Recent clinical trials of these two drugs for SARS-CoV-2 treatment revealed antiviral efficacies as well as side effects with different extents1–4. As a pyrazine derivative, Favipiravir could be incorporated into the viral RNA products by mimicking both adenine and guanine nucleotides, which may further lead to mutations in progeny RNA copies due to the non-conserved base-pairing capacity5. Here, we determined the cryo-EM structure of Favipiravir bound to the replicating polymerase complex of SARS-CoV-2 in the pre-catalytic state. This structure provides a missing snapshot for visualizing the catalysis dynamics of coronavirus polymerase, and reveals an unexpected base-pairing pattern between Favipiravir and pyrimidine residues which may explain its capacity for mimicking both adenine and guanine nucleotides. These findings shed lights on the mechanism of coronavirus polymerase catalysis and provide a rational basis for developing antiviral drugs to combat the SARS-CoV-2 pandemic. url: https://doi.org/10.1101/2020.10.19.345470 doi: 10.1101/2020.10.19.345470 id: cord-280994-w8dtfjel author: Peng, Qi title: Structural and biochemical characterization of nsp12-nsp7-nsp8 core polymerase complex from COVID-19 virus date: 2020-04-23 words: 2105.0 sentences: 135.0 pages: flesch: 55.0 cache: ./cache/cord-280994-w8dtfjel.txt txt: ./txt/cord-280994-w8dtfjel.txt summary: Here, we describe the near-atomic resolution structure of its core polymerase complex, consisting of nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases, and suggests the mechanism for activation by cofactors. Biochemical studies revealed reduced activity of the core polymerase complex and lower thermostability of individual subunits of COVID-19 virus as compared to that of SARS-CoV. Simultaneous 193 replacement of the nsp7 and nsp8 cofactors further enhanced the efficiency for RNA synthesis 194 to ~2.2 times of that for the SARS-CoV-2 homologous complex ( Figure 4B ). After 3 rounds of extensive 2D classification, ~924,000 particles 437 were selected for 3D classification with the density map of SARS-CoV nsp12-nsp7-nsp8 438 complex (EMDB-0520) as the reference which was low-pass filtered to 60 Å resolution. One severe acute respiratory syndrome 631 coronavirus protein complex integrates processive RNA polymerase and exonuclease activities abstract: The ongoing global pandemic of coronavirus disease 2019 (COVID-19) has caused huge number of human deaths. Currently, there are no specific drugs or vaccines available for this virus. The viral polymerase is a promising antiviral target. However, the structure of COVID-19 virus polymerase is yet unknown. Here, we describe the near-atomic resolution structure of its core polymerase complex, consisting of nsp12 catalytic subunit and nsp7-nsp8 cofactors. This structure highly resembles the counterpart of SARS-CoV with conserved motifs for all viral RNA-dependent RNA polymerases, and suggests the mechanism for activation by cofactors. Biochemical studies revealed reduced activity of the core polymerase complex and lower thermostability of individual subunits of COVID-19 virus as compared to that of SARS-CoV. These findings provide important insights into RNA synthesis by coronavirus polymerase and indicate a well adaptation of COVID-19 virus towards humans with relatively lower body temperatures than the natural bat hosts. url: https://doi.org/10.1101/2020.04.23.057265 doi: 10.1101/2020.04.23.057265 id: cord-293274-ysr1l557 author: Perisé-Barrios, Ana Judith title: Humoral response to SARS-CoV-2 by healthy and sick dogs during COVID-19 pandemic in Spain date: 2020-09-22 words: 4140.0 sentences: 267.0 pages: flesch: 54.0 cache: ./cache/cord-293274-ysr1l557.txt txt: ./txt/cord-293274-ysr1l557.txt summary: Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. abstract: COVID-19 is a zoonotic disease originated by SARS-CoV-2. Infection of animals with SARS-CoV-2 are being reported during last months, and also an increase of severe lung pathologies in domestic dogs has been detected by veterinarians in Spain. Therefore it is necessary to describe the pathological processes in those animals that show symptoms similar to those described in humans affected by COVID-19. The potential for companion animals contributing to the continued human-to-human disease, infectivity, and community spread is an urgent issue to be considered. Forty animals with pulmonary pathologies were studied by chest X-ray, ultrasound study, and computed tomography. Nasopharyngeal and rectal swab were analyzed to detect canine pathogens, including SARS-CoV-2. Twenty healthy dogs living in SARS-CoV-2 positive households were included. Immunoglobulin detection by different immunoassays was performed. Our findings show that sick dogs presented severe alveolar or interstitial pattern, with pulmonary opacity, parenchymal abnormalities, and bilateral lesions. Forty dogs were negative for SARS-CoV-2 but Mycoplasma spp. was detected in 26 of 33 dogs. Five healthy and one pathological dog presented IgG against SARS-CoV-2. Here we report that despite detecting dogs with IgG α-SARS-CoV-2, we never obtained a positive RT-qPCR, not even in dogs with severe pulmonary disease; suggesting that even in the case of a canine infection transmission would be unlikely. Moreover, dogs living in COVID-19 positive households could have been more exposed to be infected during outbreaks. url: https://doi.org/10.1101/2020.09.22.308023 doi: 10.1101/2020.09.22.308023 id: cord-102219-d3gkfo7s author: Perzel Mandell, Kira A. title: Characterizing the dynamic and functional DNA methylation landscape in the developing human cortex date: 2019-10-30 words: 5038.0 sentences: 231.0 pages: flesch: 47.0 cache: ./cache/cord-102219-d3gkfo7s.txt txt: ./txt/cord-102219-d3gkfo7s.txt summary: In the present report, we describe the use of whole genome bisulfite sequencing (WGBS) to capture an unbiased map of the DNAm landscape, and to characterize both CpG and CpH methylation during prenatal brain development. We performed whole genome bisulfite sequencing (WGBS) to better characterize the shifting DNAm landscape in the developing human dorsolateral prefrontal cortex (DLPFC) in 20 prenatal samples during the second trimester in utero (Table S1 ). We found that DNAm changes were abundant even during this relatively restricted period in prenatal development, with 36,546 CpG sites differentially methylated across the ages of 14-20 post-conception weeks (PCW, at FDR < 0.05, Table S3 ). The top biological processes associated with genes containing differentially methylated CpGs across age were related to axon development and guidance, and regulation of neuron projection ( Figure S4 , Table S8 ). abstract: DNA methylation (DNAm) is a key epigenetic regulator of gene expression across development. The developing prenatal brain is a highly dynamic tissue, but our understanding of key drivers of epigenetic variability across development is limited. We therefore assessed genomic methylation at over 39 million sites in the prenatal cortex using whole genome bisulfite sequencing and found loci and regions in which methylation levels are dynamic across development. We saw that DNAm at these loci was associated with nearby gene expression and enriched for enhancer chromatin states in prenatal brain tissue. Additionally, these loci were enriched for genes associated with psychiatric disorders and genes involved with neurogenesis. We also found autosomal differences in DNAm between the sexes during prenatal development, though these have less clear functional consequences. We lastly confirmed that the dynamic methylation at this critical period is specifically CpG methylation, with very low levels of CpH methylation. Our findings provide detailed insight into prenatal brain development as well as clues to the pathogenesis of psychiatric traits seen later in life. url: https://doi.org/10.1101/823781 doi: 10.1101/823781 id: cord-353911-hp6s6ebh author: Petráš, Marek title: Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein date: 2020-11-03 words: 2119.0 sentences: 134.0 pages: flesch: 54.0 cache: ./cache/cord-353911-hp6s6ebh.txt txt: ./txt/cord-353911-hp6s6ebh.txt summary: title: Early immune response in mice immunized with a semi-split inactivated vaccine against SARS-CoV-2 containing S protein-free particles and subunit S protein Our aim was to design a semi-split inactivated vaccine offering a wide range of multi-epitope determinants important for the immune system including not only the spike (S) protein but also the envelope, membrane and nucleocapsid proteins. The above laboratory procedure generated a semi-split inactivated vaccine, i.e., a vaccine with 307 the S protein separated from the viral particle exhibiting an early, both humoral and cellular, 308 immune response. Safety and immunogenicity of the ChAdOx1 nCoV-386 19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, 387 randomised controlled trial An in-depth investigation of the safety and immunogenicity of an 468 inactivated SARS-CoV-2 vaccine A double-inactivated 499 whole virus candidate SARS coronavirus vaccine stimulates neutralising and 500 protective antibody responses. Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity 526 abstract: The development of a vaccine against COVID-19 is a hot topic for many research laboratories all over the world. Our aim was to design a semi-split inactivated vaccine offering a wide range of multi-epitope determinants important for the immune system including not only the spike (S) protein but also the envelope, membrane and nucleocapsid proteins. We designed a semi-split vaccine prototype consisting of S protein-depleted viral particles and free S protein. Next, we investigated its immunogenic potential in BALB/c mice. The animals were immunized intradermally or intramuscularly with the dose adjusted with buffer or addition of aluminum hydroxide, respectively. The antibody response was evaluated by plasma analysis at 7 days after the first or second dose. The immune cell response was studied by flow cytometry analysis of splenocytes. The data showed a very early onset of both S protein-specific antibodies and virus-neutralizing antibodies at 90% inhibition regardless of the route of vaccine administration. However, significantly higher levels of neutralizing antibodies were detected in the intradermally (geometric mean titer - GMT of 7.8 ± 1.4) than in the intramuscularly immunized mice (GMT of 6.2 ± 1.5). In accordance with this, stimulation of cellular immunity by the semi-split vaccine was suggested by elevated levels of B and T lymphocyte subpopulations in the murine spleens. These responses were more predominant in the intradermally immunized mice compared with the intramuscular route of administration. The upward trend in the levels of plasmablasts, memory B cells, Th1 and Th2 lymphocytes, including follicular helper T cells, was confirmed even in mice receiving the vaccine intradermally at a dose of 0.5 μg. We demonstrated that the semi-split vaccine is capable of eliciting both humoral and cellular immunity early after vaccination. Our prototype thus represents a promising step toward the development of an efficient anti-COVID-19 vaccine for human use. url: https://doi.org/10.1101/2020.11.03.366641 doi: 10.1101/2020.11.03.366641 id: cord-349684-2tioh80m author: Pezzotti, Giuseppe title: Rapid Inactivation of SARS-CoV-2 by Silicon Nitride, Copper, and Aluminum Nitride date: 2020-06-20 words: 5388.0 sentences: 338.0 pages: flesch: 51.0 cache: ./cache/cord-349684-2tioh80m.txt txt: ./txt/cord-349684-2tioh80m.txt summary: The present study compared the effects of exposing SARS-CoV-2 to aqueous suspensions of Si3N4 and aluminum nitride (AlN) particles and two controls, (i.e., a suspension of copper (Cu) particles (positive control) and a sham treatment (negative control)). In (c) and (d), results of RT-PCR tests for supernatants after 10 min exposure of virus suspension to Cu, AlN, and Si3N4 powders for viral N gene "set 1" and "set 2" primers are shown, respectively. The present work is the first to show that compounds capable of endogenous nitrogen-release, such as Si3N4 and AlN, can inactivate the SARS-CoV-2 virus at least as effectively as Cu. These results suggest that multiple antiviral mechanisms may be operative, such as RNA fragmentation, and in the case of Cu, direct metal ion toxicity; but while Cu and AlN supernatants demonstrated strong and partial cellular lysis, respectively, Si3N4 provoked no metabolic alterations. abstract: Introduction Viral disease spread by contaminated commonly touched surfaces is a global concern. Silicon nitride, an industrial ceramic that is also used as an implant in spine surgery, has known antibacterial activity. The mechanism of antibacterial action relates to the hydrolytic release of surface disinfectants. It is hypothesized that silicon nitride can also inactivate the coronavirus SARS-CoV-2. Methods SARS-CoV-2 virions were exposed to 15 wt.% aqueous suspensions of silicon nitride, aluminum nitride, and copper particles. The virus was titrated by the TCD50 method using VeroE6/TMPRSS2 cells, while viral RNA was evaluated by real-time RT-PCR. Immunostaining and Raman spectroscopy were used as additional probes to investigate the cellular responses to virions exposed to the respective materials. Results All three tested materials showed >99% viral inactivation at one and ten minutes of exposure. Degradation of viral RNA was also observed with all materials. Immunofluorescence testing showed that silicon nitride-treated virus failed to infect VeroE6/TMPRSS2 cells without damaging them. In contrast, the copper-treated virus suspension severely damaged the cells due to copper ion toxicity. Raman spectroscopy indicated differential biochemical cellular changes due to infection and metal toxicity for two of the three materials tested. Conclusions Silicon nitride successfully inactivated the SARS-CoV-2 in this study. The mechanism of action was the hydrolysis-mediated surface release of nitrogen-containing disinfectants. Both aluminum nitride and copper were also effective in the inactivation of the virus. However, while the former compound affected the cells, the latter compound had a cytopathic effect. Further studies are needed to validate these findings and investigate whether silicon nitride can be incorporated into personal protective equipment and commonly touched surfaces, as a strategy to discourage viral persistence and disease spread. url: https://doi.org/10.1101/2020.06.19.159970 doi: 10.1101/2020.06.19.159970 id: cord-104161-jvbgouv8 author: Pfrieger, Frank W. title: Insight into the workforce advancing fields of science and technology date: 2020-06-02 words: 3052.0 sentences: 197.0 pages: flesch: 47.0 cache: ./cache/cord-104161-jvbgouv8.txt txt: ./txt/cord-104161-jvbgouv8.txt summary: Context-specific, but citation-independent metrics gauge team impact and reveal key contributors valuing publication output, mentorship and collaboration. Based on scientific articles related to a specific topic, this approach reveals instantly the teams working in a research field, visualizes workforce growth, delineates family and collaborative connections and gauges team performance in a citation-independent manner. A PubMed query using the term "circadian clock" (Clock) yielded a list of articles published between 1960 and 2020, from which TTA identified principal investigators (PIs)/teams working in the field based on last author names (Table 1 ; Supplementary Data 1). The Clock field expanded steadily in terms of workforce and of publication output as indicated by annual counts of newly entering teams and of published articles, respectively (Fig. 1A) . Individual PIs/teams published up to 113 articles (PC, publication count) as last authors (Last) with a maximum annual output of nearly 7 papers per year. abstract: Advances in biomedicine and other fields of science and technology depend on research teams and their peer-reviewed publications. The scientific literature represents an invaluable socioeconomic resource guiding future research. Typically, this growing body of information is explored by queries in bibliographic databases concerning topics of interest and by subsequent scrutiny of matching publications. This approach informs readily about content, but leaves the workforce driving the field largely unexplored. The hurdle can be overcome by a transparent team-centered analysis that visualizes the teams working in a field of interest and that delineates their genealogic and collaborative relations. Context-specific, but citation-independent metrics gauge team impact and reveal key contributors valuing publication output, mentorship and collaboration. The new insight into the structure, dynamics and performance of the workforce driving research in distinct disciplines complements ongoing efforts to mine the scientific literature, foster collaboration, evaluate research and guide future policies and investments. url: https://doi.org/10.1101/2020.06.01.128355 doi: 10.1101/2020.06.01.128355 id: cord-103830-pu6v53oy author: Pichon, Fabien title: Analysis and annotation of genome-wide DNA methylation patterns in two nonhuman primate species using the Infinium Human Methylation 450K and EPIC BeadChips date: 2020-05-10 words: 5439.0 sentences: 225.0 pages: flesch: 47.0 cache: ./cache/cord-103830-pu6v53oy.txt txt: ./txt/cord-103830-pu6v53oy.txt summary: In the present study, we evaluated the use of the Infinium 450K and Infinium EPIC BeadChips for genome-wide DNA methylation analyses in samples from Chlorocebus sabaeus and Macaca mulatta and conducted an in-depth analysis of the available probes for these two old world monkey genomes. We provide for each species and each microarray a list of annotated probes that can be used by the scientific community for genome-wide DNA methylation studies in Chlorocebus sabaeus or Macaca mulatta. We then mapped all the 50 bp probe sequences targeting CpG positions in the human genome from the Infinium 450K and EPIC arrays to Chlorocebus sabaeus (CS) and Macaca mulatta (MM) genomes, consecutively, using Bowtie [39], allowing only a unique position on the respective genome and up to 3 mismatches. abstract: The Infinium Human Methylation450 and Methylation EPIC BeadChips are useful tools for the study of the methylation state of hundreds of thousands of CpG across the human genome at affordable cost. However, in a wide range of experimental settings in particular for studies in infectious or brain-related diseases, human samples cannot be easily obtained. Hence, due to their close developmental, immunological and neurological proximity with humans, non-human primates are used in many research fields of human diseases and for preclinical research. Few studies have used DNA methylation microarrays in simian models. Microarrays designed for the analysis of DNA methylation patterns in the human genome could be useful given the genomic proximity between human and nonhuman primates. However, there is currently information lacking about the specificity and usability of each probe for many nonhuman primate species, including rhesus macaques (Macaca mulatta), originating from Asia, and African green monkeys originating from West-Africa (Chlorocebus sabaeus). Rhesus macaques and African green monkeys are among the major nonhuman primate models utilized in biomedical research. Here, we provide a precise evaluation and re-annotation of the probes of the two microarrays for the analysis of genome-wide DNA methylation patterns in these two Cercopithecidae species. We demonstrate that up to 162,000 of the 450K and 255,000 probes of the EPIC BeadChip can be reliably used in Macaca mulatta or Chlorocebus sabaeus. The annotation files are provided in a format compatible with a variety of preprocessing, normalization and analytical pipelines designed for data analysis from 450K/EPIC arrays, facilitating high-throughput DNA methylation analyses in Macaca mulatta and Chlorocebus sabaeus. They provide the opportunity to the research community to focus their analysis only on those probes identified as reliable. The described analytical workflow leaves the choice to the user to balance coverage versus specificity and can also be applied to other Cercopithecidae species. url: https://doi.org/10.1101/2020.05.09.081547 doi: 10.1101/2020.05.09.081547 id: cord-275173-ely3aen3 author: Pickering, Brad S. title: Susceptibility of domestic swine to experimental infection with SARS-CoV-2 date: 2020-09-10 words: 1917.0 sentences: 107.0 pages: flesch: 52.0 cache: ./cache/cord-275173-ely3aen3.txt txt: ./txt/cord-275173-ely3aen3.txt summary: The work reported here aims to determine whether domestic swine are susceptible to 63 SARS-CoV-2 infection, providing critical information to aid public health risk assessments. The data presented in 66 this study provides evidence live SARS-CoV-2 virus can persist in swine for at least 13 days 67 following experimental inoculation. Two pigs (20-10, 20-11) displayed low 237 levels of viral RNA by RT-qPCR at 3 DPI (Table 2, Detection of SARS-CoV-2 was also attempted from whole blood by RT-qPCR, following 253 the sampling schedule outlined in Table 1 . To identify potential target tissues or gross lesions consistent with SARS-CoV-2 disease, 261 necropsy was performed on two animals starting at 3 DPI and every other day up to day 15; with 262 an additional two pigs necropsied at both 22 and 29 DPI (Table 1) (Table 2) . The results presented in this study define domestic swine as a susceptible species albeit at 293 low levels to SARS-CoV-2 viral infection. abstract: SARS-CoV-2, the agent responsible for COVID-19 has been shown to infect a number of species. The role of domestic livestock and the risk associated for humans in close contact remains unknown for many production animals. Determination of the susceptibility of pigs to SARS-CoV-2 is critical towards a One Health approach to manage the potential risk of zoonotic transmission. Here, pigs undergoing experimental inoculation are susceptible to SARS-CoV-2 at low levels. Viral RNA was detected in group oral fluids and nasal wash from at least two animals while live virus was isolated from a pig. Further, antibodies could be detected in two animals at 11 and 13 days post infection, while oral fluid samples at 6 days post inoculation indicated the presence of secreted antibodies. These data highlight the need for additional livestock assessment to better determine the potential role domestic animals may contribute towards the SARS-CoV-2 pandemic. url: https://doi.org/10.1101/2020.09.10.288548 doi: 10.1101/2020.09.10.288548 id: cord-261718-zqoggwnk author: Pietschmann, Jan title: Brief Communication: Magnetic Immuno-Detection of SARS-CoV-2 specific Antibodies date: 2020-06-03 words: 1188.0 sentences: 76.0 pages: flesch: 45.0 cache: ./cache/cord-261718-zqoggwnk.txt txt: ./txt/cord-261718-zqoggwnk.txt summary: Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. After addition of 176 biotinylated GaR and subsequent labelling with streptavidin-AP, the ELISA plate was read out at 177 405 nm and obtained measuring values were used to generate calibration curves for SARS-CoV-2 178 specific antibody concentrations in PBS (Fig 1, black curve) and in human serum samples (Fig 1, red 179 curve). Same calibration measurements employing dilutions of SARS-CoV-2 specific antibody were 211 done with our PoC MInD-based setup (Fig 2 and 3) . Comparable to laboratory-based ELISA, the same 212 dilutions of SARS-CoV-2 spike protein peptide specific antibody in PBS-buffer (Fig 3, black abstract: SARS-CoV-2 causes ongoing infections worldwide, and identifying people with immunity is becoming increasingly important. Available point-of-care diagnostic systems as lateral flow assays have high potential for fast and easy on-site antibody testing but are lacking specificity, sensitivity or possibility for quantitative measurements. Here, a new point-of-care approach for SARS-CoV-2 specific antibody detection in human serum based on magnetic immuno-detection is described and compared to standard ELISA. For magnetic immuno-detection, immunofiltration columns were coated with a SARS-CoV-2 spike protein peptide. SARS-CoV-2 peptide reactive antibodies, spiked at different concentrations into PBS and human serum, were rinsed through immunofiltration columns. Specific antibodies were retained within the IFC and labelled with an isotype specific biotinylated antibody. Streptavidin-functionalized magnetic nanoparticles were applied to label the secondary antibodies. Enriched magnetic nanoparticles were then detected by means of frequency magnetic mixing detection technology, using a portable magnetic read-out device. Measuring signals corresponded to the amount of SARS-CoV-2 specific antibodies in the sample. Our preliminary magnetic immuno-detection setup resulted in a higher sensitivity and broader detection range and was four times faster than ELISA. Further optimizations could reduce assay times to that of a typical lateral flow assay, enabling a fast and easy approach, well suited for point-of-care measurements without expensive lab equipment. url: https://doi.org/10.1101/2020.06.02.131102 doi: 10.1101/2020.06.02.131102 id: cord-262958-tmp6yxlv author: Pinto, Dora title: Structural and functional analysis of a potent sarbecovirus neutralizing antibody date: 2020-04-09 words: 2241.0 sentences: 147.0 pages: flesch: 55.0 cache: ./cache/cord-262958-tmp6yxlv.txt txt: ./txt/cord-262958-tmp6yxlv.txt summary: The SARS-CoV-2 spike (S) glycoprotein 26 promotes entry into host cells and is the main target of neutralizing antibodies. None of the mAbs studied bound to 97 prefusion OC43 S or MERS-CoV S ectodomain trimers, indicating a lack of cross-98 reactivity outside the sarbecovirus subgenus (Extended Data Fig.1) . The structural data explain the S309 cross-reactivity between SARS-CoV-2 and 148 SARS-CoV as 19 out of 24 residues of the epitope are strictly conserved ( Fig. 2f and 149 Extended Data Fig. 6a To further investigate the mechanism of S309-mediated neutralization, we 175 compared side-by-side transduction of SARS-CoV-2-MLV in the presence of either 176 S309 Fab or S309 IgG. This analysis 208 identified at least four antigenic sites within the S B domain of SARS-CoV targeted by 209 our panel of mAbs. The receptor-binding motif, which is targeted by S230, S227 and 210 S110, is termed site I. abstract: SARS-CoV-2 is a newly emerged coronavirus responsible for the current COVID-19 pandemic that has resulted in more than one million infections and 73,000 deaths1,2. Vaccine and therapeutic discovery efforts are paramount to curb the pandemic spread of this zoonotic virus. The SARS-CoV-2 spike (S) glycoprotein promotes entry into host cells and is the main target of neutralizing antibodies. Here we describe multiple monoclonal antibodies targeting SARS-CoV-2 S identified from memory B cells of a SARS survivor infected in 2003. One antibody, named S309, potently neutralizes SARS-CoV-2 and SARS-CoV pseudoviruses as well as authentic SARS-CoV-2 by engaging the S receptor-binding domain. Using cryo-electron microscopy and binding assays, we show that S309 recognizes a glycan-containing epitope that is conserved within the sarbecovirus subgenus, without competing with receptor attachment. Antibody cocktails including S309 along with other antibodies identified here further enhanced SARS-CoV-2 neutralization and may limit the emergence of neutralization-escape mutants. These results pave the way for using S309 and S309-containing antibody cocktails for prophylaxis in individuals at high risk of exposure or as a post-exposure therapy to limit or treat severe disease. url: https://www.ncbi.nlm.nih.gov/pubmed/32511354/ doi: 10.1101/2020.04.07.023903 id: cord-313247-55loucvc author: Pipes, Lenore title: Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny date: 2020-10-07 words: 2546.0 sentences: 209.0 pages: flesch: 64.0 cache: ./cache/cord-313247-55loucvc.txt txt: ./txt/cord-313247-55loucvc.txt summary: We investigate several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution. There are many different methods for inferring the root of a phylogenetic tree, but they largely depend on three possible sources of information: outgroups, the molecular clock, and non-reversibility. To investigate the possible rootings of the SARS-CoV-2 phylogeny we used six different methods and quantified the uncertainty in the placement of the root for each method on the inferred maximum likelihood topology. We note that while interpretation of bootstrap proportions in phylogenetics can be problematic (see Efron et al., 1996) we performed 1,000 parametric simulations using pyvolve (Spielman and Wilke, 2015) using maximum likelihood estimates, from the original data set, of the model of molecular evolution and the phylogenetic tree, including branch lengths (see Table S2 ). abstract: The rooting of the SARS-CoV-2 phylogeny is important for understanding the origin and early spread of the virus. Previously published phylogenies have used different rootings that do not always provide consistent results. We investigate several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. We show that methods based on the molecular clock tend to place the root in the B clade, while methods based on outgroup rooting tend to place the root in the A clade. The results from the two approaches are statistically incompatible, possibly as a consequence of deviations from a molecular clock or excess back-mutations. We also show that none of the methods provide strong statistical support for the placement of the root in any particular edge of the tree. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution. url: https://doi.org/10.1101/2020.06.19.160630 doi: 10.1101/2020.06.19.160630 id: cord-272626-bw9lbzvt author: Pizzorno, Andrés title: Characterization and treatment of SARS-CoV-2 in nasal and bronchial human airway epithelia date: 2020-04-02 words: 2051.0 sentences: 116.0 pages: flesch: 40.0 cache: ./cache/cord-272626-bw9lbzvt.txt txt: ./txt/cord-272626-bw9lbzvt.txt summary: Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Developed from biopsies of nasal or bronchial cells differentiated in the air/liquid interphase, these models reproduce with high fidelity most of the main structural, functional and innate immune features of the human respiratory epithelium that play a central role 70 in the early stages of infection and constitute robust surrogates to study airway disease mechanisms and for drug discovery (10) . Comparably, daily treatment with 20 µM remdesivir resulted in 7.3 log10 and 7.9 log10 reductions of intracellular SARS-CoV-2 viral titers at 48 hpi in nasal and bronchial HAE, respectively (Fig. 4D, upper panel) . abstract: In the current COVID-19 pandemic context, proposing and validating effective treatments represents a major challenge. However, the lack of biologically relevant pre-clinical experimental models of SARS-CoV-2 infection as a complement of classic cell lines represents a major barrier for scientific and medical progress. Here, we advantageously used human reconstituted airway epithelial models of nasal or bronchial origin to characterize viral infection kinetics, tissue-level remodeling of the cellular ultrastructure and transcriptional immune signatures induced by SARS-CoV-2. Our results underline the relevance of this model for the preclinical evaluation of antiviral candidates. Foremost, we provide evidence on the antiviral efficacy of remdesivir and the therapeutic potential of the remdesivir-diltiazem combination as a rapidly available option to respond to the current unmet medical need imposed by COVID-19. One Sentence Summary New insights on SARS-CoV-2 biology and drug combination therapies against COVID-19. url: https://doi.org/10.1101/2020.03.31.017889 doi: 10.1101/2020.03.31.017889 id: cord-287205-k64svq6n author: Pollet, Jeroen title: SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice date: 2020-11-05 words: 4245.0 sentences: 282.0 pages: flesch: 56.0 cache: ./cache/cord-287205-k64svq6n.txt txt: ./txt/cord-287205-k64svq6n.txt summary: title: SARS-CoV-2 RBD219-N1C1: A Yeast-Expressed SARS-CoV-2 Recombinant Receptor-Binding Domain Candidate Vaccine Stimulates Virus Neutralizing Antibodies and T-cell Immunity in Mice Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as a suitable vaccine candidate against COVID-19. The modified SARS-CoV-2 antigen, 264 RBD219-N1C1, when formulated on Alhydrogel ® , was shown to induce virus-neutralizing antibodies 265 in mice, equivalent to those levels elicited by the wild-type (RBD219-WT) recombinant protein 266 counterpart. Here we report on a yeast-expressed SARS-CoV-2 RBD219-N1C1 protein and its potential as a 397 vaccine candidate antigen for preventing COVID-19. In a mouse virus challenge model for the SARS CoV RBD recombinant protein vaccine, we 422 found that Alhydrogel ® formulations induced high levels of protective immunity but did not 423 stimulate eosinophilic immune enhancement, suggesting that Alhydrogel ® may even reduce immune The selection of the P. abstract: There is an urgent need for an accessible and low-cost COVID-19 vaccine suitable for low- and middle-income countries. Here we report on the development of a SARS-CoV-2 receptor-binding domain (RBD) protein, expressed at high levels in yeast (Pichia pastoris), as a suitable vaccine candidate against COVID-19. After introducing two modifications into the wild-type RBD gene to reduce yeast-derived hyperglycosylation and improve stability during protein expression, we show that the recombinant protein, RBD219-N1C1, is equivalent to the wild-type RBD recombinant protein (RBD219-WT) in an in vitro ACE-2 binding assay. Immunogenicity studies of RBD219-N1C1 and RBD219-WT proteins formulated with Alhydrogel® were conducted in mice, and, after two doses, both the RBD219-WT and RBD219-N1C1 vaccines induced high levels of binding IgG antibodies. Using a SARS-CoV-2 pseudovirus, we further showed that sera obtained after a two-dose immunization schedule of the vaccines were sufficient to elicit strong neutralizing antibody titers in the 1:1,000 to 1:10,000 range, for both antigens tested. The vaccines induced IFN-γ, IL-6, and IL-10 secretion, among other cytokines. Overall, these data suggest that the RBD219-N1C1 recombinant protein, produced in yeast, is suitable for further evaluation as a human COVID-19 vaccine, in particular, in an Alhydrogel® containing formulation and possibly in combination with other immunostimulants. url: https://doi.org/10.1101/2020.11.04.367359 doi: 10.1101/2020.11.04.367359 id: cord-310477-vniokol0 author: Pontes, Camila title: Unraveling the molecular basis of host cell receptor usage in SARS-CoV-2 and other human pathogenic β-CoVs date: 2020-08-21 words: 4371.0 sentences: 197.0 pages: flesch: 46.0 cache: ./cache/cord-310477-vniokol0.txt txt: ./txt/cord-310477-vniokol0.txt summary: More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). In summary, the SDPs found within these β-CoV subgenera define a specific region of the receptor binding domains: they are part of, or in direct contact with, the ACE2 interacting surface ( A second S3Det analysis was performed on the full β-CoV MSA. On the other hand, the analysis performed on individual β-CoV subgenera, i.e. Sarbecovirus, Merbecovirus and Embecovirus subgroups, allowed a fine-grained classification into subfamily clusters that clearly reflect the functional diversification of the spike protein family, that is, the specificity to different host-cell receptors (Figure 2-3) . abstract: The recent emergence of the novel SARS-CoV-2 in China and its rapid spread in the human population has led to a public health crisis worldwide. Like in SARS-CoV, horseshoe bats currently represent the most likely candidate animal source for SARS-CoV-2. Yet, the specific mechanisms of cross-species transmission and adaptation to the human host remain unknown. Here we show that the unsupervised analysis of conservation patterns across the β-CoV spike protein family, using sequence information alone, can provide rich information on the molecular basis of the specificity of β-CoVs to different host cell receptors. More precisely, our results indicate that host cell receptor usage is encoded in the amino acid sequences of different CoV spike proteins in the form of a set of specificity determining positions (SDPs). Furthermore, by integrating structural data, in silico mutagenesis and coevolution analysis we could elucidate the role of SDPs in mediating ACE2 binding across the Sarbecovirus lineage, either by engaging the receptor through direct intermolecular interactions or by affecting the local environment of the receptor binding motif. Finally, by the analysis of coevolving mutations across a paired MSA we were able to identify key intermolecular contacts occurring at the spike-ACE2 interface. These results show that effective mining of the evolutionary records held in the sequence of the spike protein family can help tracing the molecular mechanisms behind the evolution and host-receptors adaptation of circulating and future novel β-CoVs. Significance Unraveling the molecular basis for host cell receptor usage among β-CoVs is crucial to our understanding of cross-species transmission, adaptation and for molecular-guided epidemiological monitoring of potential outbreaks. In the present study, we survey the sequence conservation patterns of the β-CoV spike protein family to identify the evolutionary constraints shaping the functional specificity of the protein across the β-CoV lineage. We show that the unsupervised analysis of statistical patterns in a MSA of the spike protein family can help tracing the amino acid space encoding the specificity of β-CoVs to their cognate host cell receptors. We argue that the results obtained in this work can provide a framework for monitoring the evolution of SARS-CoV-2 specificity to the hACE2 receptor, as the virus continues spreading in the human population and differential virulence starts to arise. url: https://doi.org/10.1101/2020.08.21.260745 doi: 10.1101/2020.08.21.260745 id: cord-310017-c8rd714a author: Popa, Alexandra title: Mutational dynamics and transmission properties of SARS-CoV-2 superspreading events in Austria date: 2020-07-17 words: 5572.0 sentences: 330.0 pages: flesch: 49.0 cache: ./cache/cord-310017-c8rd714a.txt txt: ./txt/cord-310017-c8rd714a.txt summary: Moreover, we combined our deep viral genome sequencing data with epidemiologically identified chains of transmissions and family clusters together with biomathematical analyses to study genetic bottlenecks and the dynamics of genome evolution of SARS-CoV-2. We assembled SARS-CoV-2 genome sequences, constructed phylogenies and identified low 15 frequency mutations based on high-quality sequencing results with >5 million reads per sample and >80% of mapped viral reads (Fig. S2A-B) . Our pipeline was validated by experimental controls involving sample titration and technical sample replicates ( Fig. S2CTo investigate the link between local outbreaks in Austria and the global pandemic, we 20 performed phylogenetic analysis of 305 SARS-CoV-2 genomes from the Austrian cases (>96% genome coverage, >80% aligned viral reads) and 7,695 global genomes from the GISAID database (Fig. 1B, Table S1 ). 7 Dynamics of low frequency and fixed mutations in clusters Next, we sought to gain insights into the fundamental processes of SARS-CoV-2 infection by integrative analysis of viral genomes. abstract: Superspreading events shape the COVID-19 pandemic. Here we provide a national-scale analysis of SARS-CoV-2 outbreaks in Austria, a country that played a major role for virus transmission across Europe and beyond. Capitalizing on a national epidemiological surveillance system, we performed deep whole-genome sequencing of virus isolates from 576 samples to cover major Austrian SARS-CoV-2 clusters. Our data chart a map of early viral spreading in Europe, including the path from low-frequency mutations to fixation. Detailed epidemiological surveys enabled us to calculate the effective SARS-CoV-2 population bottlenecks during transmission and unveil time-resolved intra-patient viral quasispecies dynamics. This study demonstrates the power of integrating deep viral genome sequencing and epidemiological data to better understand how SARS-CoV-2 spreads through populations. Graphical Abstract url: https://doi.org/10.1101/2020.07.15.204339 doi: 10.1101/2020.07.15.204339 id: cord-325610-n3zb36am author: Postlethwait, John H. title: An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities date: 2020-09-02 words: 2690.0 sentences: 159.0 pages: flesch: 50.0 cache: ./cache/cord-325610-n3zb36am.txt txt: ./txt/cord-325610-n3zb36am.txt summary: title: An intestinal cell type in zebrafish is the nexus for the SARS-CoV-2 receptor and the Renin-Angiotensin-Aldosterone System that contributes to COVID-19 comorbidities To exploit zebrafish (Danio rerio) as a disease model to understand mechanisms regulating the RAAS and its relationship to COVID-19 comorbidities, we must first identify zebrafish orthologs and co-orthologs of human RAAS genes, and second, understand where and when these genes are expressed in specific cells in zebrafish development. Results further identified a specific intestinal cell type in zebrafish larvae as the site of expression for key RAAS components, including Ace, Ace2, the coronavirus co-receptor Slc6a19, and the Angiotensin-related peptide cleaving enzymes Anpep and Enpep. These results identify specific genes and cell types to exploit zebrafish as a disease model for understanding the mechanisms leading to COVID-19 comorbidities. SUMMARY STATEMENT Genomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics show that they act in a specialized intestinal cell type. abstract: People with underlying conditions, including hypertension, obesity, and diabetes, are especially susceptible to negative outcomes after infection with the coronavirus SARS-CoV-2. These COVID-19 comorbidities are exacerbated by the Renin-Angiotensin-Aldosterone System (RAAS), which normally protects from rapidly dropping blood pressure or dehydration via the peptide Angiotensin II (Ang II) produced by the enzyme Ace. The Ace paralog Ace2 degrades Ang II, thus counteracting its chronic effects. Ace2 is also the SARS-CoV-2 receptor. Ace, the coronavirus, and COVID-19 comorbidities all regulate Ace2, but we don’t yet understand how. To exploit zebrafish (Danio rerio) as a disease model to understand mechanisms regulating the RAAS and its relationship to COVID-19 comorbidities, we must first identify zebrafish orthologs and co-orthologs of human RAAS genes, and second, understand where and when these genes are expressed in specific cells in zebrafish development. To achieve these goals, we conducted genomic analyses and investigated single cell transcriptomes. Results showed that most human RAAS genes have an ortholog in zebrafish and some have two or more co-orthologs. Results further identified a specific intestinal cell type in zebrafish larvae as the site of expression for key RAAS components, including Ace, Ace2, the coronavirus co-receptor Slc6a19, and the Angiotensin-related peptide cleaving enzymes Anpep and Enpep. Results also identified specific vascular cell subtypes as expressing Ang II receptors, apelin, and apelin receptor genes. These results identify specific genes and cell types to exploit zebrafish as a disease model for understanding the mechanisms leading to COVID-19 comorbidities. SUMMARY STATEMENT Genomic analyses identify zebrafish orthologs of the Renin-Angiotensin-Aldosterone System that contribute to COVID-19 comorbidities and single-cell transcriptomics show that they act in a specialized intestinal cell type. url: https://doi.org/10.1101/2020.09.01.278366 doi: 10.1101/2020.09.01.278366 id: cord-273882-tqdcb3oo author: Pratibha, title: Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses date: 2020-08-21 words: 1958.0 sentences: 122.0 pages: flesch: 62.0 cache: ./cache/cord-273882-tqdcb3oo.txt txt: ./txt/cord-273882-tqdcb3oo.txt summary: title: Ubiquitous Forbidden Order in R-group classified protein sequence of SARS-CoV-2 and other viruses We report here a novel method of species characterization based upon the order of these R-group classified amino acids in the linear sequence of the side chains associated with the codon triplets. These ubiquitous forbidden orders (UFO) are unique structures of the viruses that may provide an insight into viruses'' chemical behavior and the folding patterns of the proteins. Next, we analyzed protein sequences of 26 viruses (Figures 2, 3 , and Supplementary Figures 1 -4) to search for a ubiquitous forbidden order in each one of them. Among the 26 viruses studied, we noted that the forbidden order BPAB is unique to SARS CoV-2, Rubella, and Avian IB (Figure 3) . We found that at R-group classified sequences of N, B, A, and P in these two samples are identical up to level 4 of the amino acid ordering in the protein structures (Figures 4a, d, g) . abstract: Each amino acid in a polypeptide chain has a distinctive R-group associated with it. We report here a novel method of species characterization based upon the order of these R-group classified amino acids in the linear sequence of the side chains associated with the codon triplets. In an otherwise pseudo-random sequence, we search for forbidden combinations of kth order. We applied this method to analyze the available protein sequences of various viruses including SARS-CoV-2. We found that these ubiquitous forbidden orders (UFO) are unique to each of the viruses we analyzed. This unique structure of the viruses may provide an insight into viruses’ chemical behavior and the folding patterns of the proteins. This finding may have a broad significance for the analysis of coding sequences of species in general. url: https://doi.org/10.1101/2020.08.21.261289 doi: 10.1101/2020.08.21.261289 id: cord-258914-g6pv8zz9 author: Proud, Pamela C. title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model date: 2020-09-25 words: 1191.0 sentences: 90.0 pages: flesch: 51.0 cache: ./cache/cord-258914-g6pv8zz9.txt txt: ./txt/cord-258914-g6pv8zz9.txt summary: title: Prophylactic intranasal administration of a TLR2 agonist reduces upper respiratory tract viral shedding in a SARS-CoV-2 challenge ferret model We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. The TLRs are key microbe-recognition receptors with a crucial role in 97 activation of host defence and protection from infections and therefore attractive drug 98 targets against infectious diseases [12] [13] [14] To determine whether TLR2/6 agonists are also active against SARS-CoV-2, we used In life samples were taken at days 1, 3, 5, 7, 10 and 12, with scheduled culls at days 137 3 (n=6) and end of study days 12-14 (n=18) (Fig 1A) . abstract: Respiratory viruses such as coronaviruses represent major ongoing global threats, causing epidemics and pandemics with huge economic burden. Rapid spread of virus through populations poses an enormous challenge for outbreak control. Like all respiratory viruses, the most recent novel human coronavirus SARS-CoV-2, initiates infection in the upper respiratory tract (URT). Infected individuals are often asymptomatic, yet highly infectious and readily transmit virus. A therapy that restricts initial replication in the URT has the potential to prevent progression of severe lower respiratory tract disease as well as limiting person-to-person transmission. We show that prophylactic intra-nasal administration of the TLR2/6 agonist INNA-051 in a SARS-CoV-2 ferret infection model effectively reduces levels of viral RNA in the nose and throat. The results of our study support clinical development of a therapy based on prophylactic TLR2/6 innate immune activation in the URT to reduce SARS-CoV-2 transmission and provide protection against COVID-19. url: https://doi.org/10.1101/2020.09.25.309914 doi: 10.1101/2020.09.25.309914 id: cord-255791-ghrlj6b2 author: Pruijssers, Andrea J. title: Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice date: 2020-04-27 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19. url: https://doi.org/10.1101/2020.04.27.064279 doi: 10.1101/2020.04.27.064279 id: cord-275252-4e3cn50u author: Rad SM, Ali Hosseini title: Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting date: 2020-05-16 words: 4368.0 sentences: 302.0 pages: flesch: 53.0 cache: ./cache/cord-275252-4e3cn50u.txt txt: ./txt/cord-275252-4e3cn50u.txt summary: In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. A common primary focus of mutational analysis of emerging viruses is the alteration in amino acid sequence of viral proteins that may provide enhanced or new functions for virus replication, immune avoidance, or spread. However, the potential of these mutations to impact upon RNA structure and miRNA recognition provides a basis for ongoing monitoring of viral evolution at these sites in the SARS-CoV-2 genome. abstract: The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation. url: https://doi.org/10.1101/2020.05.15.098947 doi: 10.1101/2020.05.15.098947 id: cord-311114-ggcpsjk8 author: Radhakrishnan, Chandni title: Initial insights into the genetic epidemiology of SARS-CoV-2 isolates from Kerala suggest local spread from limited introductions date: 2020-09-09 words: 4383.0 sentences: 274.0 pages: flesch: 52.0 cache: ./cache/cord-311114-ggcpsjk8.txt txt: ./txt/cord-311114-ggcpsjk8.txt summary: The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. In our analysis, we mapped the SARS-CoV-2 genetic variants obtained from Kerala genomes to the 132 primer or probes sequence and calculated the melting temperature (Tm) of the mutant with the wild type sequence. abstract: Coronavirus disease 2019 (COVID-19) rapidly spread from a city in China to almost every country in the world, affecting millions of individuals. Genomic approaches have been extensively used to understand the evolution and epidemiology of SARS-CoV-2 across the world. Kerala is a unique state in India well connected with the rest of the world through a large number of expatriates, trade, and tourism. The first case of COVID-19 in India was reported in Kerala in January 2020, during the initial days of the pandemic. The rapid increase in the COVID-19 cases in the state of Kerala has necessitated the understanding of the genetic epidemiology of circulating virus, evolution, and mutations in SARS-CoV-2. We sequenced a total of 200 samples from patients at a tertiary hospital in Kerala using COVIDSeq protocol at a mean coverage of 7,755X. The analysis identified 166 unique high-quality variants encompassing 4 novel variants and 89 new variants identified for the first time in SARS-CoV-2 samples isolated from India. Phylogenetic and haplotype analysis revealed that the circulating population of the virus was dominated (94.6% of genomes) by three distinct introductions followed by local spread, apart from identifying polytomies suggesting recent outbreaks. The genomes formed a monophyletic distribution exclusively mapping to the A2a clade. Further analysis of the functional variants revealed two variants in the S gene of the virus reportedly associated with increased infectivity and 5 variants that mapped to five primer/probe binding sites that could potentially compromise the efficacy of RT-PCR detection. To the best of our knowledge, this is the first and most comprehensive report of genetic epidemiology and evolution of SARS-CoV-2 isolates from Kerala. url: https://doi.org/10.1101/2020.09.09.289892 doi: 10.1101/2020.09.09.289892 id: cord-103683-xcsal8vk author: Rafie, K. title: The structure of enteric human adenovirus 41 - a leading cause of diarrhea in children date: 2020-10-16 words: 6635.0 sentences: 354.0 pages: flesch: 53.0 cache: ./cache/cord-103683-xcsal8vk.txt txt: ./txt/cord-103683-xcsal8vk.txt summary: The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Compared to the two other reported structures of human adenoviruses, HAdV-C5 (PDB: 6B1T (20) ) and HAdV-D26 (PDB: 5TX1(21)), the sequence identity of the capsid proteins ranges from 30-80% (Supplementary Table 3 ). The HAdV-F41 penton base undergoes assembly-induced conformational changes Located on the five-fold symmetry axes of adenovirus capsids, the penton base (PB) protein forms a homopentamer that contains integrin-binding motifs and serves as an assembly hub connecting the icosahedral capsid to the fibers (Fig. 1A) . The DNA-binding protein V is located at a conserved position at the inner face of the capsid After initial model building of the virion at pH=7.4, the asymmetric unit contained five peptide chains that still had not been assigned an identity. abstract: Human adenovirus (HAdV) types F40 and F41 are a prominent cause of diarrhea and diarrhea-associated mortality in young children worldwide. These enteric HAdVs differ strikingly in tissue tropism and pathogenicity from respiratory and ocular adenoviruses, but the structural basis for this divergence has been unknown. Here we present the first structure of an enteric HAdV - HAdV-F41 - determined by cryo-EM to a resolution of 3.8Å. The structure reveals extensive alterations to the virion exterior as compared to non-enteric HAdVs, including a unique arrangement of capsid protein IX. The structure also provides new insights into conserved aspects of HAdV architecture such as a proposed location of protein V, which links the viral DNA to the capsid, and assembly-induced conformational changes in the penton base protein. Our findings provide the structural basis for adaptation to a fundamentally different tissue tropism of enteric HAdVs. url: https://doi.org/10.1101/2020.07.01.181735 doi: 10.1101/2020.07.01.181735 id: cord-323654-9nnjex9y author: Ramachandran, Ashwin title: Electric-field-driven microfluidics for rapid CRISPR-based diagnostics and its application to detection of SARS-CoV-2 date: 2020-05-22 words: 1549.0 sentences: 115.0 pages: flesch: 62.0 cache: ./cache/cord-323654-9nnjex9y.txt txt: ./txt/cord-323654-9nnjex9y.txt summary: Unlike previous CRISPR diagnostic assays, we also use ITP for automated purification of target RNA from raw nasopharyngeal swab sample. We here combine this ITP purification with loop-mediated isothermal amplification, and the ITP-enhanced CRISPR assay to achieve detection of SARS-CoV-2 RNA (from raw sample to result) in 30 min for both contrived and clinical nasopharyngeal swab samples. We also demonstrated on-chip ITP extraction of total nucleic acids from raw clinical 175 positive and negative nasopharyngeal swab samples (Figs. We observed that ITP-extracted nucleic acids showed E gene amplification on positive qPCR-based detection approaches is provided in Table 1 . We propose here 520 the concept that such a system can integrate ITP-based nucleic acid extraction, 521 multiplexed isothermal amplification of target cDNA of N and E genes of SARS-CoV-2 522 and RNase P control, followed by ITP-CRISPR-based cDNA detection in three separate 523 channels using photodiodes. abstract: The rapid spread of COVID-19 across the world has revealed major gaps in our ability to respond to new virulent pathogens. Rapid, accurate, and easily configurable molecular diagnostic tests are imperative to prevent global spread of new diseases. CRISPR-based diagnostic approaches are proving to be useful as field-deployable solutions. In a basic form of this assay, the CRISPR-Cas12 enzyme complexes with a synthetic guide RNA (gRNA). This complex is activated when it highly specifically binds to target DNA, and the activated complex non-specifically cleaves single-stranded DNA reporter probes labeled with a fluorophore-quencher pair. We recently discovered that electric field gradients can be used to control and accelerate this CRISPR assay by co-focusing Cas12-gRNA, reporters, and target. We achieve an appropriate electric field gradient using a selective ionic focusing technique known as isotachophoresis (ITP) implemented on a microfluidic chip. Unlike previous CRISPR diagnostic assays, we also use ITP for automated purification of target RNA from raw nasopharyngeal swab sample. We here combine this ITP purification with loop-mediated isothermal amplification, and the ITP-enhanced CRISPR assay to achieve detection of SARS-CoV-2 RNA (from raw sample to result) in 30 min for both contrived and clinical nasopharyngeal swab samples. This electric field control enables a new modality for a suite of microfluidic CRISPR-based diagnostic assays. Significance statement Rapid, early-stage screening is especially crucial during pandemics for early identification of infected patients and control of disease spread. CRISPR biology offers new methods for rapid and accurate pathogen detection. Despite their versatility and specificity, existing CRISPR-diagnostic methods suffer from the requirements of up-front nucleic acid extraction, large reagent volumes, and several manual steps—factors which prolong the process and impede use in low resource settings. We here combine on-chip electric-field control in combination with CRIPSR biology to directly address these limitations of current CRISPR-diagnostic methods. We apply our method to the rapid detection of SARS-CoV-2 RNA in clinical samples. Our method takes 30 min from raw sample to result, a significant improvement over existing diagnostic methods for COVID-19. url: https://doi.org/10.1101/2020.05.21.109637 doi: 10.1101/2020.05.21.109637 id: cord-103625-p55ew8w7 author: Ramana, Chilakamarti V. title: Regulation of early growth response-1 (Egr-1) gene expression by Stat1-independent type I interferon signaling and respiratory viruses date: 2020-08-14 words: 3320.0 sentences: 217.0 pages: flesch: 47.0 cache: ./cache/cord-103625-p55ew8w7.txt txt: ./txt/cord-103625-p55ew8w7.txt summary: Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. In this study, transcription factor profiling in interferon-mediated gene expression data sets and RT-PCR revealed that Egr-1 was rapidly induced by IFN-α/β and TLR ligands in multiple cell types. Respiratory pathogens including coronaviruses (SARS-CoV-1 and 2) and influenza viruses regulated the expression of Egr-1 in human lung cell lines and in lung biopsies and peripheral blood cells of COVID-19 patients, These studies suggest that the regulation of Egr-1 may play an important role in the antiviral response and inflammatory disease. abstract: Respiratory virus infection is one of the leading causes of death in the world. Activation of the Jak-Stat pathway by Interferon-alpha/beta (IFN-α/β) in lung epithelial cells is critical for innate immunity to respiratory viruses. Genetic and biochemical studies have shown that transcriptional regulation by IFN-α/β required the formation of Interferon-stimulated gene factor-3 (ISGF-3) complex consisting of Stat1, Stat2, and Irf9 transcription factors. Furthermore, IFN α/β receptor activates multiple signal transduction pathways in parallel to the Jak-Stat pathway and induces several transcription factors at mRNA levels resulting in the secondary and tertiary rounds of transcription. Transcriptional factor profiling in the transcriptome and RNA analysis revealed that Early growth response-1 (Egr-1) was rapidly induced by IFN-α/β and Toll-like receptor (TLR) ligands in multiple cell types. Studies in mutant cell lines lacking components of the ISGF-3 complex revealed that IFN-β induction of Egr-1 was independent of Stat1, Stat2, or Irf9. Activation of the Mek/Erk-1/2 pathway was implicated in the rapid induction of Egr-1 by IFN-β in serum-starved mouse lung epithelial cells. Interrogation of multiple microarray datasets revealed that respiratory viruses including coronaviruses regulated Egr-1 expression in human lung cell lines. Furthermore, Egr-1 inducible genes including transcription factors, mediators of cell growth, and chemokines were differentially regulated in the human lung cell lines after coronavirus infection, and in the lung biopsies of COVID-19 patients. Rapid induction by interferons, TLR ligands, and respiratory viruses suggests a critical role for Egr-1 in antiviral response and inflammation with potential implications for human health and disease. url: https://doi.org/10.1101/2020.08.14.244897 doi: 10.1101/2020.08.14.244897 id: cord-252597-ea78sjcs author: Ramazzotti, Daniele title: VERSO: a comprehensive framework for the inference of robust phylogenies and the quantification of intra-host genomic diversity of viral samples date: 2020-10-19 words: 10701.0 sentences: 502.0 pages: flesch: 45.0 cache: ./cache/cord-252597-ea78sjcs.txt txt: ./txt/cord-252597-ea78sjcs.txt summary: Moreover, the in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and allows us to identify a number of variants that are transiting from minor to clonal state in the population, as well as several homoplasies, some of which might indicate ongoing positive selection processes. The outbreak of coronavirus disease 2019 (COVID19) , which started in late 2019 in Wuhan (China) [1, 2] and was declared pandemic by the World Health Organization, is fueling the publication of an increasing number of studies aimed at exploiting the information provided by the viral genome of SARS-CoV-2 virus to identify its proximal origin, characterize the mode and timing of its evolution, as well as to define descriptive and predictive models of geographical spread and evaluate the related clinical impact [3, 4, 5] . abstract: A global cross-discipline effort is ongoing to characterize the evolution of SARS-CoV-2 virus and generate reliable epidemiological models of its diffusion. To this end, phylogenomic approaches leverage accumulating genomic mutations to track the evolutionary history of the virus and benefit from the surge of sequences deposited in public databases. Yet, such methods typically rely on consensus sequences representing the dominant virus lineage, whereas a complex intra-host genomic composition is often observed within single hosts. Furthermore, most approaches might produce inaccurate results with noisy data and sampling limitations, as witnessed in most countries affected by the epidemics. We introduce VERSO (Viral Evolution ReconStructiOn), a new comprehensive framework for the characterization of viral evolution and transmission from sequencing data of viral genomes. Our probabilistic approach first delivers robust phylogenetic models from clonal variant profiles and then exploits variant frequency patterns to characterize and visualize the intra-host genomic diversity of samples, which may reveal uncovered infection events. We prove via extensive simulations that VERSO outperforms the state-of-the-art tools for phylogenetic inference, also in condition of noisy observations and sampling limitations. The application of our approach to 3960 SARS-CoV-2 samples from Amplicon sequencing and to 2766 samples from RNA-sequencing unravels robust phylogenomic models, improving the current knowledge on SARS-CoV-2 evolution and spread. Importantly, by exploiting co-occurrence patterns of minor variants, VERSO allows us to reveal uncovered infection paths, which are validated with contact tracing data. Moreover, the in-depth analysis of the mutational landscape of SARS-CoV-2 confirms a statistically significant increase of genomic diversity in time and allows us to identify a number of variants that are transiting from minor to clonal state in the population, as well as several homoplasies, some of which might indicate ongoing positive selection processes. Overall, the results show that the joint application of our framework and data-driven epidemiological models might improve currently available strategies for pathogen surveillance and analysis. VERSO is released as an open source tool at https://github.com/BIMIB-DISCo/VERSO. url: https://doi.org/10.1101/2020.04.22.044404 doi: 10.1101/2020.04.22.044404 id: cord-260315-uau554jj author: Ramirez, Santseharay title: Efficient culture of SARS-CoV-2 in human hepatoma cells enhances viability of the virus in human lung cancer cell lines permitting the screening of antiviral compounds date: 2020-10-04 words: 2269.0 sentences: 122.0 pages: flesch: 54.0 cache: ./cache/cord-260315-uau554jj.txt txt: ./txt/cord-260315-uau554jj.txt summary: title: Efficient culture of SARS-CoV-2 in human hepatoma cells enhances viability of the virus in human lung cancer cell lines permitting the screening of antiviral compounds Culture adaptation in Huh7.5 cells further permitted efficient infection of the otherwise SARS-CoV-2 refractory human lung cancer cell line A549, with titers of ~6 Log10TCID50/mL. Importance The cell culture adapted variant of the SARS-CoV-2 virus obtained in the present study, showed significantly enhanced replication and propagation in various human cell lines, including lung derived cells otherwise refractory for infection with the original virus. Further, as shown here with the use of remdesivir and EIDD-2801, two nucs with significant inhibitory effect against SARS-CoV-2, large differences in the antiviral activity are observed depending on the cell line. 137 We performed a comparative titration in various cells of the P2 VeroE6 and the P5 Huh7.5 viruses ( Figure 138 1b) and found that the infectivity titers in Huh7.5 cells after culture adaptation had increased by more 139 than 3 logs (mean of 4.7 and 8.0 Log 10 TCID 50 /mL, respectively). abstract: Efforts to mitigate COVID-19 include screening of existing antiviral molecules that could be re-purposed to treat SARS-CoV-2 infections. Although SARS-CoV-2 propagates efficiently in African green monkey kidney (Vero) cells, antivirals such as nucleos(t)ide analogs (nucs) often exhibit decreased activity in these cells due to inefficient metabolization. Limited SARS-CoV-2 replication and propagation occurs in human cells, which are the most relevant testing platforms. By performing serial passages of a SARS-CoV-2 isolate in the human hepatoma cell line clone Huh7.5, we selected viral populations with improved viability in human cells. Culture adaptation led to the emergence of a significant number of high frequency changes (>90% of the viral population) in the region coding for the spike glycoprotein, including a deletion of nine amino acids in the N-terminal domain and 3 amino acid changes (E484D, P812R, and Q954H). We demonstrated that the Huh7.5-adapted virus exhibited a >3-Log10 increase in infectivity titers (TCID50) in Huh7.5 cells, with titers of ~8 Log10TCID50/mL, and >2-Log10 increase in the human lung cancer cell line Calu-1, with titers of ~6 Log10TCID50/mL. Culture adaptation in Huh7.5 cells further permitted efficient infection of the otherwise SARS-CoV-2 refractory human lung cancer cell line A549, with titers of ~6 Log10TCID50/mL. The enhanced ability of the virus to replicate and propagate in human cells permitted screening of a panel of nine nucs, including broad-spectrum compounds. Remdesivir, EIDD-2801 and to a limited extent galidesivir showed antiviral effect across these human cell lines, whereas sofosbuvir, uprifosbuvir, valopicitabine, mericitabine, ribavirin, and favipiravir had no apparent activity. Importance The cell culture adapted variant of the SARS-CoV-2 virus obtained in the present study, showed significantly enhanced replication and propagation in various human cell lines, including lung derived cells otherwise refractory for infection with the original virus. This SARS-CoV-2 variant will be a valuable tool permitting investigations across human cell types, and studies of identified mutations could contribute to our understanding of viral pathogenesis. In particular, the adapted virus can be a good model for investigations of viral entry and cell tropism for SARS-CoV-2, in which the spike glycoprotein plays a central role. Further, as shown here with the use of remdesivir and EIDD-2801, two nucs with significant inhibitory effect against SARS-CoV-2, large differences in the antiviral activity are observed depending on the cell line. Thus, it is essential to select the most relevant target cells for pre-clinical screenings of antiviral compounds, facilitated by using a virus with broader tropism. url: https://doi.org/10.1101/2020.10.04.325316 doi: 10.1101/2020.10.04.325316 id: cord-346978-ubkqny8j author: Ranoa, Diana Rose E. title: Saliva-Based Molecular Testing for SARS-CoV-2 that Bypasses RNA Extraction date: 2020-06-18 words: 6476.0 sentences: 325.0 pages: flesch: 54.0 cache: ./cache/cord-346978-ubkqny8j.txt txt: ./txt/cord-346978-ubkqny8j.txt summary: 35 Using intact, γ-irradiated SARS-CoV-2 spiked into fresh human saliva, which was then heat treated at 95°C for 30 min, we observed outstanding virus detection when saliva samples were combined with either Tris-Borate-EDTA (TBE) or TE buffer ( Figure 3A) . Similar results were observed with heat-inactivated SARS-CoV-2, whereby the LOD was measured to be 5000 viral copies/mL for both RNA extraction of saliva samples and direct saliva-to-RT-qPCR, with greater detection if the virus was directly analyzed in water (Supporting Limit of Detection (LOD) for assessment of SARS-CoV-2 from saliva, comparing a process utilizing RNA isolation/purification to one that bypasses RNA isolation/purification. Altogether, these findings indicate that the optimized protocol (heat treatment of saliva samples at 95°C for 30 min / addition of TBE buffer and Tween 20) yields a LOD that is comparable to reported clinical viral shedding concentrations in oral fluid, thus emphasizing the translatability of the protocol to detecting SARS-CoV-2 in patient samples. abstract: Convenient, repeatable, large-scale molecular testing for SARS-CoV-2 would be a key weapon to help control the COVID-19 pandemic. Unfortunately, standard SARS-CoV-2 testing protocols are invasive and rely on numerous items that can be subject to supply chain bottlenecks, and as such are not suitable for frequent repeat testing. Specifically, personal protective equipment (PPE), nasopharyngeal (NP) swabs, the associated viral transport media (VTM), and kits for RNA isolation and purification have all been in short supply at various times during the COVID-19 pandemic. Moreover, SARS-CoV-2 is spread through droplets and aerosols transmitted through person-to-person contact, and thus saliva may be a relevant medium for diagnosing SARS-CoV-2 infection status. Here we describe a saliva-based testing method that bypasses the need for RNA isolation/purification. In experiments with inactivated SARS-CoV-2 virus spiked into saliva, this method has a limit of detection of 500-1000 viral particles per mL, rivalling the standard NP swab method, and initial studies also show excellent performance with 100 clinical samples. This saliva-based process is operationally simple, utilizes readily available materials, and can be easily implemented by existing testing sites, thus allowing for high-throughput, rapid, and repeat testing of large populations. Graphical Abstract url: https://doi.org/10.1101/2020.06.18.159434 doi: 10.1101/2020.06.18.159434 id: cord-329395-4k8js9v2 author: Ratcliff, Jeremy title: Evaluation of Different PCR Assay Formats for Sensitive and Specific Detection of SARS-CoV-2 RNA date: 2020-07-01 words: 1662.0 sentences: 124.0 pages: flesch: 55.0 cache: ./cache/cord-329395-4k8js9v2.txt txt: ./txt/cord-329395-4k8js9v2.txt summary: Polymerase chain reaction (PCR)-based assays are the gold standard for detecting viral RNA in patient samples and are used extensively in clinical settings. To enable the application of PCR in resource-poor or non-specialist laboratories, we have developed and evaluated a nested PCR method for SARS-CoV-2 RNA using simple agarose gel electrophoresis for product detection. Using clinical samples tested by conventional qPCR methods and RNA transcripts of defined RNA copy number, the nested PCR based on the RdRP gene demonstrated high sensitivity and specificity for SARS-CoV-2 RNA detection in clinical samples, but showed variable and transcript length-dependent sensitivity for RNA transcripts. The sensitivity of the nested PCR and two RT-qPCR methods was compared by measuring the 118 50% endpoints (50EP) of detection for serial dilutions of the four transcripts described above 119 (Table 1, Figure 2 ). Protocol: Real-time RT-PCR assays for the detection of SARS-CoV-2 abstract: Accurate identification of individuals infected with SARS-CoV-2 is crucial for efforts to control the ongoing COVID-19 pandemic. Polymerase chain reaction (PCR)-based assays are the gold standard for detecting viral RNA in patient samples and are used extensively in clinical settings. Most currently used quantitative PCR (RT-qPCRs) rely upon real-time detection of PCR product using specialized laboratory equipment. To enable the application of PCR in resource-poor or non-specialist laboratories, we have developed and evaluated a nested PCR method for SARS-CoV-2 RNA using simple agarose gel electrophoresis for product detection. Using clinical samples tested by conventional qPCR methods and RNA transcripts of defined RNA copy number, the nested PCR based on the RdRP gene demonstrated high sensitivity and specificity for SARS-CoV-2 RNA detection in clinical samples, but showed variable and transcript length-dependent sensitivity for RNA transcripts. Samples and transcripts were further evaluated in an additional N protein real-time quantitative PCR assay. As determined by 50% endpoint detection, the sensitivities of three RT-qPCRs and nested PCR methods varied substantially depending on the transcript target with no method approaching single copy detection. Overall, these findings highlight the need for assay validation and optimization and demonstrate the inability to precisely compare viral quantification from different PCR methodologies without calibration. url: https://doi.org/10.1101/2020.06.24.168013 doi: 10.1101/2020.06.24.168013 id: cord-300194-nsp53lv6 author: Rath, Soumya Lipsa title: Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations date: 2020-06-19 words: 4302.0 sentences: 226.0 pages: flesch: 54.0 cache: ./cache/cord-300194-nsp53lv6.txt txt: ./txt/cord-300194-nsp53lv6.txt summary: Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. and S2 domains individually, with respect to the starting structure, to understand the ause for higher R S values o served at and igure The R S values of S1 domain at and were found to e around nm nearly nm more than simulations at 1 and respe tively similar trend was o served in the R S of S domain ut the differen e in values was only 1 nm lthough in this study we haven''t considered the bilayer lipid membrane of the SARS-COV-2 envelope inside which the Spike 9 glycoprotein resides, the S2 domain shows remarkable stability in its RMSD values ( Figure 2 ). abstract: Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 °C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 °C and attains a completely closed conformation at 50 °C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics. Graphical Abstract Highlights Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. Results show that the Spike’s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30° C. The Receptor Binding Motif adopts a closed conformation at 40°C and completely closes at higher temperatures making it unsuitable of binding to human receptors url: https://doi.org/10.1101/2020.06.10.145086 doi: 10.1101/2020.06.10.145086 id: cord-103055-071a5b0x author: Rathbun, LI title: PLK1- and PLK4-mediated asymmetric mitotic centrosome size and positioning in the early zebrafish embryo date: 2020-04-14 words: 3126.0 sentences: 156.0 pages: flesch: 49.0 cache: ./cache/cord-103055-071a5b0x.txt txt: ./txt/cord-103055-071a5b0x.txt summary: We propose a model in which uniquely large centrosomes direct spindle placement within the disproportionately large zebrafish embryo cells to orchestrate cell divisions during early embryogenesis. This is clearly visualized through the use of a fluorescent microtubule transgenic zebrafish line (EMTB-3xGFP) [7] , where the 16-cell stage embryo contains mitotic spindles oriented perpendicular to the previous division at the 8 In early development, rapid rounds of division result in a stark decrease in cell size during the cleavage stage [8] . Strikingly, mitotic centrosomes in zebrafish embryos were extremely large with g-tubulin organized into a wheel-like structure (246.44±11.93μm 2 at 8-cell stage, Figure 1E ), compared to g-tubulin in C. elegans and zebrafish embryos, cell length and mitotic centrosome area decreased by 30-40% over time. In order to determine the importance of PLK1/4-dependent asymmetric mitotic centrosome size placement in early zebrafish divisions, we raised embryos after injection of 1% DMSO, 1μM BI2536, or 1μM centrinone ( Figure 4F ). abstract: Factors that regulate mitotic spindle positioning have been elucidated in vitro, however it remains unclear how a spindle is placed within the confines of extremely large cells. Our studies identified a uniquely large centrosome structure in the early zebrafish embryo (246.44±11.93μm2 mitotic centrosome in a 126.86±0.35μm diameter cell), whereas C. elegans centrosomes are notably smaller (6.75±0.28μm2 mitotic centrosome in a 55.83±1.04μm diameter cell). During early embryonic cell divisions, cell size changes rapidly in C. elegans and zebrafish embryos. Notably, mitotic centrosome area scales closely with changing cell size compared to changes in spindle length for both organisms. One interesting difference between the two is that mitotic centrosomes are asymmetric in size across embryonic zebrafish spindles, with the larger mitotic centrosome being 2.14±0.13-fold larger in size than the smaller. The largest mitotic centrosome is placed towards the embryo center in a Polo-Like Kinase (PLK) 1 and PLK4 dependent manner 87.14±4.16% of the time. We propose a model in which uniquely large centrosomes direct spindle placement within the disproportionately large zebrafish embryo cells to orchestrate cell divisions during early embryogenesis. url: https://doi.org/10.1101/2020.04.13.039362 doi: 10.1101/2020.04.13.039362 id: cord-278869-7zr1118b author: Ravichandran, Supriya title: Antibody repertoire induced by SARS-CoV-2 spike protein immunogens date: 2020-05-13 words: 2370.0 sentences: 142.0 pages: flesch: 52.0 cache: ./cache/cord-278869-7zr1118b.txt txt: ./txt/cord-278869-7zr1118b.txt summary: To better understand antibody response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). The spike ectodomain (S1+S2) generated antibodies that predominantly bound to S1+S2 108 6 (black bar), followed by the S1 protein (blue bar), and 3-fold lower antibody binding to the RBD 109 and the S2 domain (red and green bars, respectively) (Fig. 1D ). Antibody off-rate constants, which describe the fraction of antigen-antibody complexes 119 that decay per second, were determined directly from the serum sample interaction with SARS-120 CoV-2 spike ectodomain (S1+S2), S1, S2, and RBD using SPR in the dissociation phase only for 121 sensorgrams with Max RU in the range of 20-100 RU (Suppl. abstract: Multiple vaccine candidates against SARS-CoV-2 based on viral spike protein are under development. However, there is limited information on the quality of antibody response generated following vaccination by these vaccine modalities. To better understand antibody response induced by spike protein-based vaccines, we immunized rabbits with various SARS-CoV-2 spike protein antigens: S-ectodomain (S1+S2) (aa 16-1213), which lacks the cytoplasmic and transmembrane domains (CT-TM), the S1 domain (aa 16-685), the receptor-binding domain (RBD) (aa 319-541), and the S2 domain (aa 686-1213 as control). Antibody response was analyzed by ELISA, Surface Plasmon Resonance (SPR) against different Spike proteins in native conformation, and a pseudovirion neutralization assay to measure the quality and function of the antibodies elicited by the different Spike antigens. All three antigens (S1+S2 ectodomain, S1 domain, and RBD) generated strong neutralizing antibodies against SARS-CoV-2. Vaccination induced antibody repertoire was analyzed by SARS-CoV-2 spike Genome Fragment Phage Display Libraries (SARS-CoV-2 GFPDL), which identified immunodominant epitopes in the S1, S1-RBD and S2 domains. Furthermore, these analyses demonstrated that surprisingly the RBD immunogen elicited a higher antibody titer with 5-fold higher affinity antibodies to native spike antigens compared with other spike antigens. These findings may help guide rational vaccine design and facilitate development and evaluation of effective therapeutics and vaccines against COVID-19 disease. One Sentence Summary SARS-CoV-2 Spike induced immune response url: https://doi.org/10.1101/2020.05.12.091918 doi: 10.1101/2020.05.12.091918 id: cord-310464-lkdkdque author: Rayko, Mikhail title: Quality control of low-frequency variants in SARS-CoV-2 genomes date: 2020-05-07 words: 1702.0 sentences: 109.0 pages: flesch: 58.0 cache: ./cache/cord-310464-lkdkdque.txt txt: ./txt/cord-310464-lkdkdque.txt summary: During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. As a result of the collaborative efforts of the researchers worldwide, on April 14, 2020 it contained over 8,000 SARS-nCoV-2 genomes from different countries, sequenced and assembled using various technologies and approaches. GISAID database curators do a tremendous job of filtering submitted sequences, but sometimes it is difficult to distinguish real variants from errors, especially at the lack of information about coverage. Dataset 8,053 full-length (>29,000 bp) sequences of the SARS-CoV-2 were downloaded from the GISAID database ( www.epicov.org ) on April 14, 2020, including 5,556 genomes marked as "high coverage". Full table with percentage of singleton-containing genomes depending on sequencing and assembly method. abstract: During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission. url: https://doi.org/10.1101/2020.04.26.062422 doi: 10.1101/2020.04.26.062422 id: cord-261435-wcn4bjnw author: Ren, Xianwen title: Large-scale single-cell analysis reveals critical immune characteristics of COVID-19 patients date: 2020-10-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dysfunctional immune response in the COVID-19 patients is a recurrent theme impacting symptoms and mortality, yet the detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 205 COVID-19 patients and controls to create a comprehensive immune landscape. Lymphopenia and active T and B cell responses were found to coexist and associated with age, sex and their interactions with COVID-19. Diverse epithelial and immune cell types were observed to be virus-positive and showed dramatic transcriptomic changes. Elevation of ANXA1 and S100A9 in virus-positive squamous epithelial cells may enable the initiation of neutrophil and macrophage responses via the ANXA1-FPR1 and S100A8/9-TLR4 axes. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis and designing effective therapeutic strategies for COVID-19. HIGHLIGHTS Large-scale scRNA-seq analysis depicts the immune landscape of COVID-19 Lymphopenia and active T and B cell responses coexist and are shaped by age and sex SARS-CoV-2 infects diverse epithelial and immune cells, inducing distinct responses Cytokine storms with systemic S100A8/A9 are associated with COVID-19 severity url: https://doi.org/10.1101/2020.10.29.360479 doi: 10.1101/2020.10.29.360479 id: cord-267845-18hb5ndr author: Resende, Paola Cristina title: SARS-CoV-2 genomes recovered by long amplicon tiling multiplex approach using nanopore sequencing and applicable to other sequencing platforms date: 2020-05-01 words: 1616.0 sentences: 89.0 pages: flesch: 48.0 cache: ./cache/cord-267845-18hb5ndr.txt txt: ./txt/cord-267845-18hb5ndr.txt summary: Here, we describe three protocols using a unique primer set designed to recover long reads of SARS-CoV-2 directly from total RNA extracted from clinical samples. Despite those limitations, we developed a sequencing protocol that successfully obtained whole genomes from SARS-CoV-2 positive samples referred to the National Reference laboratory at FIOCRUZ in Brazil. The tiling amplicon multiplex PCR method has been previously used for virus sequencing directly from clinical samples to obtain consensus genome sequences (3). Here, we describe three protocols using a primer set designed to sequence SARS-CoV-2 directly from total RNA extracted from clinical samples, which were initially diagnosed using real-time RT-PCR (7, 8) . Here we introduce a versatile sequencing protocol to recover the complete SARS-CoV-2 genome based on reverse transcription plus an overlapping long amplicon multiplex PCR strategy, and associated with pipelines to report the data, and recover the consensus files. Multiplex PCR method for MinION and Illumina sequencing of Zika and other virus genomes directly from clinical samples abstract: Genomic surveillance has become a useful tool for better understanding virus pathogenicity, origin and spread. Obtaining accurately assembled, complete viral genomes directly from clinical samples is still a challenging. Here, we describe three protocols using a unique primer set designed to recover long reads of SARS-CoV-2 directly from total RNA extracted from clinical samples. This protocol is useful, accessible and adaptable to laboratories with varying resources and access to distinct sequencing methods: Nanopore, Illumina and/or Sanger. url: https://doi.org/10.1101/2020.04.30.069039 doi: 10.1101/2020.04.30.069039 id: cord-313505-2lr4xara author: Resende, Paola Cristina title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil date: 2020-06-18 words: 1145.0 sentences: 99.0 pages: flesch: 55.0 cache: ./cache/cord-313505-2lr4xara.txt txt: ./txt/cord-313505-2lr4xara.txt summary: title: Genomic surveillance of SARS-CoV-2 reveals community transmission of a major lineage during the early pandemic phase in Brazil Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. Introduction 59 COVID-19, the disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 60 (SARS-CoV-2), is leading to high rates of acute respiratory syndrome, hospitalization, and death 61 genomes (> 10% of ambiguous positions), we obtained a final dataset of 7,674 sequences. The prevalence of the sub-clade 211 B.1.1 in our sample (92%) was much higher than that observed in other Brazilian sequences 212 available in GISAID (36%) (Fig. 1C) phylogenetic tree, consistent with the hypothesis of multiple independent introductions (Fig. 2) (Fig. 2) . Revealing COVID-19 Transmission by SARS-CoV-2 Genome 410 Sequencing and Agent Based Modelling. abstract: Despite all efforts to control the COVID-19 spread, the SARS-CoV-2 reached South America within three months after its first detection in China, and Brazil became one of the hotspots of COVID-19 in the world. Several SARS-CoV-2 lineages have been identified and some local clusters have been described in this early pandemic phase in Western countries. Here we investigated the genetic diversity of SARS-CoV-2 during the early phase (late February to late April) of the epidemic in Brazil. Phylogenetic analyses revealed multiple introductions of SARS-CoV-2 in Brazil and the community transmission of a major B.1.1 lineage defined by two amino acid substitutions in the Nucleocapsid and ORF6. This SARS-CoV-2 Brazilian lineage was probably established during February 2020 and rapidly spread through the country, reaching different Brazilian regions by the middle of March 2020. Our study also supports occasional exportations of this Brazilian B.1.1 lineage to neighboring South American countries and to more distant countries before the implementation of international air travels restrictions in Brazil. url: https://doi.org/10.1101/2020.06.17.158006 doi: 10.1101/2020.06.17.158006 id: cord-269285-2r40mico author: Resnick, Samuel J. title: A simplified cell-based assay to identify coronavirus 3CL protease inhibitors date: 2020-08-29 words: 1941.0 sentences: 126.0 pages: flesch: 60.0 cache: ./cache/cord-269285-2r40mico.txt txt: ./txt/cord-269285-2r40mico.txt summary: We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. In general, we observe concordance between compounds showing activity within 129 this transfection-based 3CL assay and live virus studies ( Supplementary Fig. 4a -e) 13 . The other hit from the 169 screen, GRL-0496, shares structural similarity to several other compounds within the library, one of 170 which is a previously reported 3CLpro inhibitor (MAC-5576) that failed to show activity against 5.05 µM against SARS-CoV-2 3CLpro within our transfection-based assay (Fig. 4c ). . https://doi.org/10.1101/2020.08.29.272864 doi: bioRxiv preprint we propose that this cellular protease assay system could be industrialized to screen and optimize a 219 large number of compounds to discover potential treatments for future viral pandemics. abstract: We describe a mammalian cell-based assay capable of identifying coronavirus 3CL protease (3CLpro) inhibitors without requiring the use of live virus. By enabling the facile testing of compounds across a range of coronavirus 3CLpro enzymes, including the one from SARS-CoV-2, we are able to quickly identify compounds with broad or narrow spectra of activity. We further demonstrate the utility of our approach by performing a curated compound screen along with structure-activity profiling of a series of small molecules to identify compounds with antiviral activity. Throughout these studies, we observed concordance between data emerging from this assay and from live virus assays. By democratizing the testing of 3CL inhibitors to enable screening in the majority of laboratories rather than the few with extensive biosafety infrastructure, we hope to expedite the search for coronavirus 3CL protease inhibitors, to address the current epidemic and future ones that will inevitably arise. url: https://doi.org/10.1101/2020.08.29.272864 doi: 10.1101/2020.08.29.272864 id: cord-102444-n4vdxdhp author: Rhea, Elizabeth M. title: The S1 protein of SARS-CoV-2 crosses the blood-brain barrier: Kinetics, distribution, mechanisms, and influence of ApoE genotype, sex, and inflammation date: 2020-07-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Evidence strongly suggests that SARS-CoV-2, the cause of COVID-19, can enter the brain. SARS-CoV-2 enters cells via the S1 subunit of its spike protein, and S1 can be used as a proxy for the uptake patterns and mechanisms used by the whole virus; unlike studies based on productive infection, viral proteins can be used to precisely determine pharmacokinetics and biodistribution. Here, we found that radioiodinated S1 (I-S1) readily crossed the murine blood-brain barrier (BBB). I-S1 from two commercial sources crossed the BBB with unidirectional influx constants of 0.287 ± 0.024 μL/g-min and 0.294 ± 0.032 μL/g-min and was also taken up by lung, spleen, kidney, and liver. I-S1 was uniformly taken up by all regions of the brain and inflammation induced by lipopolysaccharide reduced uptake in the hippocampus and olfactory bulb. I-S1 crossed the BBB completely to enter the parenchymal brain space, with smaller amounts retained by brain endothelial cells and the luminal surface. Studies on the mechanisms of transport indicated that I-S1 crosses the BBB by the mechanism of adsorptive transcytosis and that the murine ACE2 receptor is involved in brain and lung uptake, but not that by kidney, liver, or spleen. I-S1 entered brain after intranasal administration at about 1/10th the amount found after intravenous administration and about 0.66% of the intranasal dose entered blood. ApoE isoform or sex did not affect whole brain uptake, but had variable effects on olfactory bulb, liver, spleen, and kidney uptakes. In summary, I-S1 readily crosses the murine BBB, entering all brain regions and the peripheral tissues studied, likely by the mechanism of adsorptive transcytosis. Graphical Abstract url: https://doi.org/10.1101/2020.07.15.205229 doi: 10.1101/2020.07.15.205229 id: cord-102565-egtbzhg7 author: Richards, Gareth title: Assortative Mating, Autistic Traits, Empathizing, and Systemizing date: 2020-10-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: It has been suggested that the children of parents with particular interests and aptitude for understanding systems via input-operation-output rules (i.e. systemizing) are at increased likelihood of developing autism. Furthermore, assortative mating (i.e. a non-random pattern in which individuals are more likely to pair with others who are similar to themselves) is hypothesised to occur in relation to systemizing, and so romantic couples may be more similar on this variable than chance would dictate. However, no published study has yet tested this hypothesis. We therefore examined intra-couple correlations for a measure of autistic traits (Autism Spectrum Quotient [AQ]), self-report measures of empathizing (Empathy Quotient [EQ]), and systemizing (Systemizing Quotient-Revised [SQ-R]), as well as the Reading the Mind in the Eyes Test (RMET) and Embedded Figures Task (EFT). We observed positive intra-couple correlations of small-to-medium magnitude for all measures except EQ. Further analyses suggest that these effects are attributable to people pairing with those who are more similar to themselves than chance (initial assortment) rather than becoming more alike over the course of a relationship (convergence), and to seeking out self-resembling partners (active assortment) rather than pairing in this manner due to social stratification increasing the likelihood of similar people meeting in the first place (social homogamy). Additionally, we found that the difference in scores for the AQ, SQ-R, RMET and EFT of actual couples were smaller (i.e. more similar) than the average difference scores calculated from all other possible male-female pairings within the dataset. The current findings therefore provide clear evidence in support of the assortative mating theory of autism. url: https://doi.org/10.1101/2020.10.28.358895 doi: 10.1101/2020.10.28.358895 id: cord-103432-cdmoazrl author: Richardson, Eve title: A computational method for immune repertoire mining that identifies novel binders from different clonotypes, demonstrated by identifying anti-Pertussis toxoid antibodies date: 2020-06-02 words: 6556.0 sentences: 375.0 pages: flesch: 51.0 cache: ./cache/cord-103432-cdmoazrl.txt txt: ./txt/cord-103432-cdmoazrl.txt summary: To test the ability of paratyping and clonotyping to group antibodies that target the same epitope we performed a test in a single-cell (paired VH/VL) data set of 1290 antibodies isolated from genetically engineered mice that have a full set of human immunoglobulin variable region genes [31] immunised with Pertussis toxoid (PTx). Each of the PTx-binders is referred to as a "probe" antibody; sequences that are within the same paratype or clonotype as the probe are predicted to bind PTx. The precision and recall of the two methods (calculated over the aggregate of predictions) for repertoire mining are comparable ( Figure 2 , Table 1 ). In a test system of transgenic mice immunised with Pertussis toxoid (PTx), we show for the first time that prediction and comparison of paratopes can be used to group antigen-specific antibodies in both an enriched, single-cell data set and non-enriched bulk heavy chain repertoires. abstract: Due to their shared genetic history, antibodies from the same clonotype often bind to the same epitope. This knowledge is used in immune repertoire mining, where known binders are used to search bulk sequencing repertoires to identify new binders. However current computational methods cannot identify epitope convergence between antibodies from different clonotypes, limiting the sequence diversity of antigen-specific antibodies which can be identified. We describe how the antibody binding site, the paratope, can be used to cluster antibodies with common antigen reactivity from different clonotypes. Our method, paratyping, uses the predicted paratope to identify these novel cross clonotype matches. We experimentally validated our predictions on a Pertussis toxoid dataset. Our results show that even the simplest abstraction of the antibody binding site, using only the length of the loops involved and predicted binding residues, is sufficient to group antigen-specific antibodies and provide additional information to conventional clonotype analysis. url: https://doi.org/10.1101/2020.06.02.121129 doi: 10.1101/2020.06.02.121129 id: cord-342599-558yn6pu author: Rinchai, Darawan title: A modular framework for the development of targeted Covid-19 blood transcript profiling panels date: 2020-05-22 words: 5230.0 sentences: 298.0 pages: flesch: 42.0 cache: ./cache/cord-342599-558yn6pu.txt txt: ./txt/cord-342599-558yn6pu.txt summary: Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. In this proof of principle study, we used the available transcript profiling data from two separate studies to select Covid-19 relevant sets of modules (8, 9) . One of these applications provides access to module-level transcript abundance profiles for available Covid-19 blood transcriptome profiling datasets. Despite large differences between the two studies in terms of design, range of clinical severity, technology platforms and module coverage, the combined overall changes (detected at a high-level perspective) are consistent with those observed in known acute infections, such as those caused by influenza, respiratory syncytial virus (RSV) or S. abstract: Covid-19 morbidity and mortality are associated with a dysregulated immune response. Tools are needed to enhance existing immune profiling capabilities in affected patients. Here we aimed to develop an approach to support the design of focused blood transcriptome panels for profiling the immune response to SARS-CoV-2 infection. We designed a pool of candidates based on a pre-existing and well-characterized repertoire of blood transcriptional modules. Available Covid-19 blood transcriptome data was also used to guide this process. Further selection steps relied on expert curation. Additionally, we developed several custom web applications to support the evaluation of candidates. As a proof of principle, we designed three targeted blood transcript panels, each with a different translational connotation: therapeutic development relevance, SARS biology relevance and immunological relevance. Altogether the work presented here may contribute to the future expansion of immune profiling capabilities via targeted profiling of blood transcript abundance in Covid-19 patients. url: https://doi.org/10.1101/2020.05.20.107243 doi: 10.1101/2020.05.20.107243 id: cord-102898-eyyd7ent author: Rizvi, Vaseef A. title: Translation regulation of Japanese encephalitis virus revealed by ribosome profiling date: 2020-07-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Japanese encephalitis virus (JEV), a neurotropic flavivirus, is the leading cause of viral encephalitis in endemic regions of Asia. Although the mechanisms modulating JEV virulence and neuroinvasiveness are poorly understood, several acquired mutations in the live attenuated vaccine strain (SA14-14-2) point towards translation regulation as a key strategy. Using ribosome profiling, we identify multiple mechanisms including frameshifting, tRNA dysregulation and alternate translation initiation sites that regulate viral protein synthesis. A significant fraction (~ 40%) of ribosomes undergo frameshifting on NS1 coding sequence leading to early termination, translation of NS1′ protein and modulation of viral protein stoichiometry. Separately, a tRNA subset (glutamate, serine, leucine and histidine) was found to be associated in high levels with the ribosomes upon JEV infection. We also report a previously uncharacterised translational initiation event from an upstream UUG initiation codon in JEV 5′ UTR. A silent mutation at this start site in the vaccine strain has been shown to abrogate neuroinvasiveness suggesting the potential role of translation from this region. Together, our study sheds light on distinct mechanisms that modulate JEV translation with likely consequences for viral pathogenesis. url: https://doi.org/10.1101/2020.07.16.206920 doi: 10.1101/2020.07.16.206920 id: cord-343586-28ezisog author: Rocca, María Florencia title: A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs date: 2020-05-07 words: 1498.0 sentences: 78.0 pages: flesch: 47.0 cache: ./cache/cord-343586-28ezisog.txt txt: ./txt/cord-343586-28ezisog.txt summary: title: A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms as an alternative fast tool for SARS-CoV-2 detection from nasopharyngeal swabs samples. According to our preliminary results, mass spectrometry-based methods combined with multivariate analysis showed an interesting potential as a complementary diagnostic tool and further steps should be focused on sample preparation protocols and the improvement of the technology applied. These preliminary results suggest that MALDI-TOF MS coupled with ClinProTools software represents an interesting alternative as a screening tool for diagnosis of SARS-CoV-2, especially because of the good performance and accuracy obtained with samples in which viral presence was not detected. abstract: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid, sensitive and specific diagnosis of SARS-CoV-2 by fast and unambiguous testing is widely recognized to be critical in responding to the ongoing outbreak. Since the current testing capacity of RT-PCR-based methods is being challenged due to the extraordinary demand of supplies, such as RNA extraction kits and PCR reagents worldwide, alternative and/or complementary testing assays should be developed. Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms as an alternative fast tool for SARS-CoV-2 detection from nasopharyngeal swabs samples. According to our preliminary results, mass spectrometry-based methods combined with multivariate analysis showed an interesting potential as a complementary diagnostic tool and further steps should be focused on sample preparation protocols and the improvement of the technology applied. url: https://doi.org/10.1101/2020.05.07.082925 doi: 10.1101/2020.05.07.082925 id: cord-288644-ywaefpe8 author: Rodon, Jordi title: Pre-clinical search of SARS-CoV-2 inhibitors and their combinations in approved drugs to tackle COVID-19 pandemic date: 2020-10-20 words: 7571.0 sentences: 449.0 pages: flesch: 50.0 cache: ./cache/cord-288644-ywaefpe8.txt txt: ./txt/cord-288644-ywaefpe8.txt summary: We have tested the antiviral activity of different clinically available compounds and their combinations by assessing their ability to inhibit viral induced cytopathic effect in vitro. Drug selection criteria first focused on compounds already being tested in clinical trials, along with well-known human immunodeficiency virus-1 (HIV-1) and hepatitis C virus (HCV) protease inhibitors, as well as other compounds suggested to have potential activity against SARS-CoV-2 in molecular docking analysis or in vitro assays. Additional Food and Drug Administration (FDA)-approved compounds previously used to abrogate viral entry via clathrin-mediated endocytosis were also tested in this SARS-CoV-2-induced cytotoxicity assay (Supp . Cytopathic effect on Vero E6 cells exposed to a fixed concentration of SARS-CoV-2 in the presence of increasing concentrations of plitidepsin and its combinations with hydroxychloroquine and remdesivir. abstract: There is an urgent need to identify novel drugs against the new coronavirus. Although different antivirals are given for the clinical management of SARS-CoV-2 infection, their efficacy is still under evaluation. Here, we have screened existing drugs approved for human use in a variety of diseases, to compare how they counteract SARS-CoV-2-induced cytopathic effect and viral replication in vitro. Among the potential 72 antivirals tested herein that were previously proposed to inhibit SARS-CoV-2 infection, only 18% had in vitro antiviral activity. Moreover, only eight families had an IC50 below 25 µM or 102 IU/mL. These include chloroquine derivatives and remdesivir, along with plitidepsin, cathepsin inhibitors, nelfinavir mesylate hydrate, interferon 2-alpha, interferon-gamma, fenofibrate and camostat. Plitidepsin was the only clinically approved drug displaying nanomolar efficacy. Four of these families, including novel cathepsin inhibitors, blocked viral entry in a cell-type specific manner. Since the most effective antivirals usually combine therapies that tackle the virus at different steps of infection, we also assessed several drug combinations. Although no particular synergy was found, inhibitory combinations did not reduce their antiviral activity. Thus, these combinations could decrease the potential emergence of resistant viruses. Antivirals prioritized herein identify novel compounds and their mode of action, while independently replicating the activity of a reduced proportion of drugs which are mostly approved for clinical use. Combinations of these drugs should be tested in animal models to inform the design of fast track clinical trials. url: https://doi.org/10.1101/2020.04.23.055756 doi: 10.1101/2020.04.23.055756 id: cord-353161-mtq6yh25 author: Rodrigues, João PGLM title: Insights on cross-species transmission of SARS-CoV-2 from structural modeling date: 2020-06-05 words: 6169.0 sentences: 369.0 pages: flesch: 56.0 cache: ./cache/cord-353161-mtq6yh25.txt txt: ./txt/cord-353161-mtq6yh25.txt summary: We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Collectively, our results provide a structural framework that explains why certain animal species are not susceptible to SARS-CoV-2 infection, and also suggests potential mutations that can enhance binding to the viral RBD. Although it is well-known that docking scores do not quantitatively correlate with experimental binding affinities [19] , these scores suggest that SARS-CoV-2 neg species lack one or more key ACE2 residues that contribute significantly to the interaction with RBD. Models of SARS-CoV-2 neg species -chicken, duck, guinea pig, mouse, and rat -generally have higher (worse) HADDOCK scores than average (Figure 2 ), suggesting that these species'' non-susceptibility to infection could stem from deficient RBD binding to ACE2. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results. url: https://www.ncbi.nlm.nih.gov/pubmed/32577636/ doi: 10.1101/2020.06.05.136861 id: cord-102383-m5ahicqb author: Romano, Alessandra title: Energy dynamics for systemic configurations of virus-host co-evolution date: 2020-05-15 words: 3776.0 sentences: 190.0 pages: flesch: 43.0 cache: ./cache/cord-102383-m5ahicqb.txt txt: ./txt/cord-102383-m5ahicqb.txt summary: A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. abstract: Virus cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, and convey in virion assembly to ensure virus spread in the body. Study of the systemic behavior of virus-host interaction at the single-cell level is a scientific challenge, considering the difficulties of using experimental approaches and the limited knowledge of the behavior of emerging novel virus as a collectivity. This work focuses on positive-sense, single-stranded RNA viruses, like human coronaviruses, in their virus-individual host interaction, studying the changes induced in the host cell bioenergetics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the system energy dynamics. We found that reducing the energy flow which fuels virion assembly is the most affordable strategy to limit the virus spread, but its efficacy is mitigated by the contemporary inhibition of other flows relevant for the system. Summary Positive-single-strand ribonucleic acid ((+)ssRNA) viruses can cause multiple outbreaks, for which comprehensive tailored therapeutic strategies are still missing. Virus and host cell dynamics are strictly connected, generating a complex dynamics that conveys in virion assembly to ensure virus spread in the body. This work focuses on (+)ssRNA viruses in their virus-individual host interaction, studying the changes induced in the host cell bioenergetics. A systems-thinking representation, based on stock-flow diagramming of virus-host interaction at the cellular level, is used here for the first time to simulate the energy dynamics of the system. By means of a computational simulator based on the systemic diagramming, we identifid host protein recycling and folded-protein synthesis as possible new leverage points. These also address different strategies depending on time setting of the therapeutic procedures. Reducing the energy flow which fuels virion assembly is addressed as the most affordable strategy to limit the virus spread, but its efficacy is mitigated by the contemporary inhibition of other flows relevant for the system. Counterintuitively, targeting RNA replication or virion budding does not give rise to relevant systemic effects, and can possibly contribute to further virus spread. The tested combinations of multiple systemic targets are less efficient in minimizing the stock of virions than targeting only the virion assembly process, due to the systemic configuration and its evolution overtime. Viral load and early addressing (in the first two days from infection) of leverage points are the most effective strategies on stock dynamics to minimize virion assembly and preserve host-cell bioenergetics. As a whole, our work points out the need for a systemic approach to design effective therapeutic strategies that should take in account the dynamic evolution of the system. url: https://doi.org/10.1101/2020.05.13.092866 doi: 10.1101/2020.05.13.092866 id: cord-347472-n6811ens author: Rosebrock, Adam P. title: Patient DNA cross-reactivity of the CDC SARS-CoV-2 extraction control leads to an inherent potential for false negative results date: 2020-05-15 words: 6252.0 sentences: 344.0 pages: flesch: 51.0 cache: ./cache/cord-347472-n6811ens.txt txt: ./txt/cord-347472-n6811ens.txt summary: The US Centers for Disease Control and Prevention (CDC) have specified and given emergency use authorization (EUA) for a SARS-CoV-2 molecular diagnostic used to detect viral RNA in clinical samples (2) . Genomic DNA is co-purified in quantities sufficient to generate strong positive signals for the CDC-specified extraction control during work-up of clinical RNA specimens. To test for the presence of control-affecting DNA, qPCR reactions lacking reverse transcriptase were performed on SARS-CoV-2-positive clinical samples using the CDC-specified RP primer and probe. All clinical samples tested generated unambiguous extraction control positive signals in the absence of reverse transcription, a reaction context that could not have detected virus an RNA virus ( Fig. 2A) Single-digit copies of genomic DNA are sufficient to generate a positive control signal using the CDC-designed assay. Due to the presence of co-purifying genomic DNA in clinical samples, loss of RNA integrity leads to false-negative results using the CDC-specified control. abstract: Testing for RNA viruses such as SARS-CoV-2 requires careful handling of inherently labile RNA during sample collection, clinical processing, and molecular analysis. Tests must include fail-safe controls that affirmatively report the presence of intact RNA and demonstrate success of all steps of the assay. A result of “no virus signal” is insufficient for clinical interpretation: controls must also say “The reaction worked as intended and would have found virus if present.” Unfortunately, a widely used test specified by the US Centers for Disease Control and Prevention (CDC) incorporates a control that does not perform as intended and claimed. Detecting SARS-CoV-2 with this assay requires both intact RNA and successful reverse transcription. The CDC-specified control does not require either of these, due to its inability to differentiate human genomic DNA from reverse-transcribed RNA. Patient DNA is copurified from nasopharyngeal swabs during clinically-approved RNA extraction and is sufficient to return an “extraction control success” signal using the CDC design. As such, this assay fails-unsafe: truly positive patient samples return a false-negative result of “no virus detected, control succeeded” following any of several readily-encountered mishaps. This problem affects tens-of-millions of patients worth of shipped assays, but many of these flawed reagents have not yet been used. There is an opportunity to improve this important diagnostic tool. As demonstrated here, a re-designed transcript-specific control correctly monitors sample collection, extraction, reverse transcription, and qPCR detection. This approach can be rapidly implemented and will help reduce truly positive patients from being incorrectly given the all-clear. One Sentence Summary A widely-used COVID-19 diagnostic is mis-designed and generates false-negative results, dangerously confusing “No” with “Don’t know” – but it’s fixable url: https://doi.org/10.1101/2020.05.13.094839 doi: 10.1101/2020.05.13.094839 id: cord-336522-y9nzsv95 author: Rosenke, Kyle title: Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino-oligomers date: 2020-09-30 words: 1723.0 sentences: 121.0 pages: flesch: 54.0 cache: ./cache/cord-336522-y9nzsv95.txt txt: ./txt/cord-336522-y9nzsv95.txt summary: title: Inhibition of SARS-CoV-2 in Vero cell cultures by peptide-conjugated morpholino-oligomers Cell viability was 33 evaluated with an ATP-based method and viral growth was measured with quantitative RT-PCR 34 and TCID50 infectivity assays. Results: PPMO designed to base-pair with sequence in the 5''-terminal region or the leader 36 transcription regulatory sequence-region of SARS-CoV-2 genomic RNA were highly 37 efficacious, reducing viral titers by up to 4-6 log10 in cell cultures at 48-72 hours post-infection, 38 in a non-toxic and dose-responsive manner. Results: PPMO designed to base-pair with sequence in the 5''-terminal region or the leader 36 transcription regulatory sequence-region of SARS-CoV-2 genomic RNA were highly 37 efficacious, reducing viral titers by up to 4-6 log10 in cell cultures at 48-72 hours post-infection, 38 in a non-toxic and dose-responsive manner. In this study, five PPMO were designed to target the 5'' UTR 107 and first translation start site-region of SARS-CoV-2 positive sense genomic RNA ( Table 1) . abstract: Background SARS-CoV-2 is the causative agent of COVID-19 and a pathogen of immense global public health importance. Development of innovative direct-acting antiviral agents is sorely needed to address this virus. Peptide-conjugated morpholino oligomers (PPMO) are antisense agents composed of a phosphordiamidate morpholino oligomer covalently conjugated to a cell-penetrating peptide. PPMO require no delivery assistance to enter cells and are able to reduce expression of targeted RNA through sequence-specific steric blocking. Objectives and Methods Five PPMO designed against sequences of genomic RNA in the SARS-CoV-2 5’-untranslated region and a negative control PPMO of random sequence were synthesized. Each PPMO was evaluated for its effect on the viability of uninfected cells and its inhibitory effect on the replication of SARS-CoV-2 in Vero-E6 cell cultures. Cell viability was evaluated with an ATP-based method and viral growth was measured with quantitative RT-PCR and TCID50 infectivity assays. Results PPMO designed to base-pair with sequence in the 5’-terminal region or the leader transcription regulatory sequence-region of SARS-CoV-2 genomic RNA were highly efficacious, reducing viral titers by up to 4-6 log10 in cell cultures at 48-72 hours post-infection, in a non-toxic and dose-responsive manner. Conclusion The data indicate that PPMO have the ability to potently and specifically suppress SARS-CoV-2 growth and are promising candidates for further pre-clinical development. url: https://doi.org/10.1101/2020.09.29.319731 doi: 10.1101/2020.09.29.319731 id: cord-309289-vm0k7hfx author: Rothan, Hussin A. title: The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells date: 2020-04-14 words: 1463.0 sentences: 91.0 pages: flesch: 46.0 cache: ./cache/cord-309289-vm0k7hfx.txt txt: ./txt/cord-309289-vm0k7hfx.txt summary: title: The FDAapproved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, antiinflammatory and anti-ROS properties. We investigated the anti-viral activity of auranofin against SARS-CoV-2 and its effect on virus-induced inflammation in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury. abstract: SARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 hours after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Auranofin has a well-known toxicity profile and is considered safe for human use. url: https://doi.org/10.1101/2020.04.14.041228 doi: 10.1101/2020.04.14.041228 id: cord-263090-29n9tsk9 author: Roy, Susmita title: Dynamical asymmetry exposes 2019-nCoV prefusion spike date: 2020-04-21 words: 4573.0 sentences: 331.0 pages: flesch: 57.0 cache: ./cache/cord-263090-29n9tsk9.txt txt: ./txt/cord-263090-29n9tsk9.txt summary: In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. B. Side and top views of the homo-trimeric structure of SARS-CoV-2 spike protein with one RBD of the S1 subunit head rotated in the up conformation. A number of Cryo-EM structures captured the ''up'' and ''down'' conformations of the RBD domain of spike proteins of other coronaviruses including SARS-CoV-2 where the S1 subunit undergoes a hinge-like conformational movement prerequisite for receptor binding (Fig. 2C) (7, 8, 10, 17) . Analysis of all the simulations yields the 2-D free energy landscape of the trimeric spike protein of SARS-CoV-2 ( Fig 3B) with its all possible conformations. This generates a homo-trimeric SARS-CoV-2 spike where this initial structure has important components in terms of intra and inter-chain contacts (interaction) leading to an ''S1-head-up'' and an ''S1-head-down'' conformation for each protomer. abstract: The novel coronavirus (2019-nCoV) spike protein is a smart molecular machine that instigates the entry of coronavirus to the host cell causing the COVID-19 pandemic. In this study, a structural-topology based model Hamiltonian of C3 symmetric trimeric spike is developed to explore its complete conformational energy landscape using molecular dynamic simulations. The study finds 2019-nCoV to adopt a unique strategy by undertaking a dynamic conformational asymmetry induced by a few unique inter-chain interactions. This results in two prevalent asymmetric structures of spike where one or two spike heads lifted up undergoing a dynamic transition likely to enhance rapid recognition of the host-cell receptor turning on its high-infectivity. The crucial interactions identified in this study are anticipated to potentially affect the efficacy of therapeutic targets. One Sentence Summary Inter-chain-interaction driven rapid symmetry breaking strategy adopted by the prefusion trimeric spike protein likely to make 2019-nCoV highly infective. url: https://doi.org/10.1101/2020.04.20.052290 doi: 10.1101/2020.04.20.052290 id: cord-306901-uuwgpuhw author: Roy, Sylvie title: Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein date: 2020-09-16 words: 4215.0 sentences: 251.0 pages: flesch: 58.0 cache: ./cache/cord-306901-uuwgpuhw.txt txt: ./txt/cord-306901-uuwgpuhw.txt summary: title: Efficient production of Moloney murine leukemia virus-like particles pseudotyped with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein Several investigational vaccines that have already been tested in animals and humans were able to induce neutralizing antibodies against the SARS-CoV-2 spike (S) protein, however protection and long-term efficacy in humans remain to be demonstrated. We have investigated if a virus-like particle (VLP) derived from Moloney murine leukemia virus (MLV) could be engineered to become a candidate SARS-CoV-2 vaccine amenable to mass production. High amounts of SARS-CoV-2 DS protein are incorporated into MLV VLPs released 142 from stable producer cells. A VLP-derived SARS CoV-2 vaccine will be a viable option if 143 sufficient amounts of S protein are incorporated at the surface of the released particles. In conclusion, we have developed and characterized a new MLV VLP platform that can 243 efficiently incorporate the S protein from SARS-CoV-2, and that has the potential to produce a pan-244 coronavirus vaccine. abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak that started in China at the end of 2019 has rapidly spread to become pandemic. Several investigational vaccines that have already been tested in animals and humans were able to induce neutralizing antibodies against the SARS-CoV-2 spike (S) protein, however protection and long-term efficacy in humans remain to be demonstrated. We have investigated if a virus-like particle (VLP) derived from Moloney murine leukemia virus (MLV) could be engineered to become a candidate SARS-CoV-2 vaccine amenable to mass production. First, we showed that a codon optimized version of the S protein could migrate efficiently to the cell membrane. However, efficient production of infectious viral particles was only achieved with stable expression of a shorter version of S in its C-terminal domain (ΔS) in 293 cells that express MLV Gag-Pol (293GP). The incorporation of ΔS was 15-times more efficient into VLPs as compared to the full-length version, and that was not due to steric interference between the S cytoplasmic tail and the MLV capsid. Indeed, a similar result was also observed with extracellular vesicles released from parental 293 and 293GP cells. The amount of ΔS incorporated into VLPs released from producer cells was robust, with an estimated 1.25 μg/ml S2 equivalent (S is comprised of S1 and S2). Thus, a scalable platform that has the potential for production of pan-coronavirus VLP vaccines has been established. The resulting nanoparticles could potentially be used alone or as a boost for other immunization strategies for COVID-19. IMPORTANCE Several candidate COVID-19 vaccines have already been tested in humans, but their protective effect and long-term efficacy are uncertain. Therefore, it is necessary to continue developing new vaccine strategies that could be more potent and/or that would be easier to manufacture in large-scale. Virus-like particle (VLP) vaccines are considered highly immunogenic and have been successfully developed for human papilloma virus as well as hepatitis and influenza viruses. In this study, we report the generation of a robust Moloney murine leukemia virus platform that produces VLPs containing the spike of SARS-CoV-2. This vaccine platform that is compatible with lyophilization could simplify storage and distribution logistics immensely. url: https://doi.org/10.1101/2020.09.16.298992 doi: 10.1101/2020.09.16.298992 id: cord-302160-4yfvspaq author: Ruetalo, Natalia title: Rapid and efficient inactivation of surface dried SARS-CoV-2 by UV-C irradiation date: 2020-10-07 words: 1853.0 sentences: 108.0 pages: flesch: 56.0 cache: ./cache/cord-302160-4yfvspaq.txt txt: ./txt/cord-302160-4yfvspaq.txt summary: Strikingly, short exposure of high titer surface dried virus (3*10^6 IU/ml) with UV-C light (16 mJ/cm2) resulted in a total reduction of SARS-CoV-2 infectivity. We hence conducted a "real-life" application approach simulating the 66 inactivation of dried surface residing infectious SARS-CoV-2 by a mobile handheld UV-C 67 emitting device and an UV-C box designed to decontaminate medium-size objects. Simulating the situation that exhaled droplets or aerosols from infected 115 individuals contaminate surfaces, we produced a high-titer SARS-CoV-2 infectious stock and 116 dried 35µL of this stock corresponding to ~4*10^6 IU/ml in each well of a 6-well plate. Of note, even short UV-C treatment of the dried virus in the context of the moving "fast" 135 regimen completely inactivated SARS-CoV-2, as no infected cells were detected based on 136 fluorescence protein expression (Fig. 1b) . Altogether, our data 143 demonstrate that UV-C regimens that expose high-titer SARS-CoV-2 to doses down to 16 144 mJ/cm² are sufficient to achieve complete inactivation of the virus. abstract: The SARS-CoV-2 pandemic urges for cheap, reliable and rapid technologies for disinfection and decontamination. We here evaluated the efficiency of UV-C irradiation to inactivate surface dried SARS-CoV-2. Drying for two hours did not have a major impact on the infectivity of SARS-CoV-2, indicating that exhaled virus in droplets or aerosols stays infectious on surfaces at least for a certain amount of time. Strikingly, short exposure of high titer surface dried virus (3*10^6 IU/ml) with UV-C light (16 mJ/cm2) resulted in a total reduction of SARS-CoV-2 infectivity. Together, our results demonstrate that SARS-CoV-2 is rapidly inactivated by relatively low doses of UV-C irradiation. Hence, UV-C treatment is an effective non-chemical possibility to decontaminate surfaces from high-titer infectious SARS-CoV-2. url: https://doi.org/10.1101/2020.09.22.308098 doi: 10.1101/2020.09.22.308098 id: cord-267482-afqfymbq author: Ryu, Seungjin title: Ketogenesis restrains aging-induced exacerbation of COVID in a mouse model date: 2020-09-12 words: 8189.0 sentences: 476.0 pages: flesch: 49.0 cache: ./cache/cord-267482-afqfymbq.txt txt: ./txt/cord-267482-afqfymbq.txt summary: Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Also, initial studies that employ lung ciliated epithelial cell-specific HFH4/FOXJ1 promoter driven hACE2 transgenic mice show SARS-CoV-2 infection induces weight loss, lung inflammation and approximately 50% mortality rate, suggesting the usefulness of this model to understand the mechanism of immune dysregulation (Jiang et al., 2020) . Moreover, given our recent findings that ketogenesis inhibits inflammation and expands tissue resident ϒδ T cells (Goldberg et al., 2019) while SARS-CoV-2 infection in patients is associated with depletion of ϒδ T cells (Lei et al., 2020; Rijkers et al., 2020) , we next tested whether elevating BHB by feeding a ketogenic diet (KD) protects against mCoV-A59-driven inflammatory damage in aged mice. abstract: Increasing age is the strongest predictor of risk of COVID-19 severity. Unregulated cytokine storm together with impaired immunometabolic response leads to highest mortality in elderly infected with SARS-CoV-2. To investigate how aging compromises defense against COVID-19, we developed a model of natural murine beta coronavirus (mCoV) infection with mouse hepatitis virus strain MHV-A59 (mCoV-A59) that recapitulated majority of clinical hallmarks of COVID-19. Aged mCoV-A59-infected mice have increased mortality and higher systemic inflammation in the heart, adipose tissue and hypothalamus, including neutrophilia and loss of γδ T cells in lungs. Ketogenic diet increases beta-hydroxybutyrate, expands tissue protective γδ T cells, deactivates the inflammasome and decreases pathogenic monocytes in lungs of infected aged mice. These data underscore the value of mCoV-A59 model to test mechanism and establishes harnessing of the ketogenic immunometabolic checkpoint as a potential treatment against COVID-19 in the elderly. Highlights - Natural MHV-A59 mouse coronavirus infection mimics COVID-19 in elderly. - Aged infected mice have systemic inflammation and inflammasome activation - Murine beta coronavirus (mCoV) infection results in loss of pulmonary γδ T cells. - Ketones protect aged mice from infection by reducing inflammation. eTOC Blurb Elderly have the greatest risk of death from COVID-19. Here, Ryu et al report an aging mouse model of coronavirus infection that recapitulates clinical hallmarks of COVID-19 seen in elderly. The increased severity of infection in aged animals involved increased inflammasome activation and loss of γδ T cells that was corrected by ketogenic diet. url: https://doi.org/10.1101/2020.09.11.294363 doi: 10.1101/2020.09.11.294363 id: cord-292985-w62xaa4f author: Römer, Rudolf A. title: Flexibility and mobility of SARS-CoV-2-related protein structures date: 2020-07-12 words: 5201.0 sentences: 341.0 pages: flesch: 61.0 cache: ./cache/cord-292985-w62xaa4f.txt txt: ./txt/cord-292985-w62xaa4f.txt summary: We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. 34 We have performed our analysis through multiple conformational steps starting from the crystal structures of SARS-CoV-2-related proteins as currently deposited in the PDB. In Fig. 1 (a) we see that for the crystal structure of SARS-CoV-2 nucleocapsid protein N-terminal RNA binding domain (PDB:6m3m), the largest rigid cluster in the pristine structure, i.e. at E cut = 0, largely remains rigid through the dilution process of consecutively lowering E cut values. Last, a protein with 2nd-order rigidity should have the most complex behaviour in terms of flexibility since new possible mobility can be expected throughout the range of E cut values. Moving along directions proposed by an elastic normal model analysis of the crystal structure, we can therefore construct possible motion trajectories that are fully consistent with the bond network and steric constraints. abstract: The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB. url: https://doi.org/10.1101/2020.07.12.199364 doi: 10.1101/2020.07.12.199364 id: cord-300783-pvn2qq0f author: Sadykov, Mukhtar title: Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction date: 2020-08-07 words: 933.0 sentences: 91.0 pages: flesch: 61.0 cache: ./cache/cord-300783-pvn2qq0f.txt txt: ./txt/cord-300783-pvn2qq0f.txt summary: title: Short sequence motif dynamics in the SARS-CoV-2 genome suggest a role for cytosine deamination in CpG reduction RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanisms are still largely unknown. Remarkably, by simply ordering SARS-CoV-2 genomes by their date of collection, we find a progressive increase of C-to-U substitutions resulting in 5''-UCG-3'' motif reduction that in turn have reduced the CpG frequency over just a few months of observation. Our results thus link the dynamics of target sequences in the viral genome for two known host molecular defense mechanisms, mediated by the APOBEC and ZAP proteins. One such 34 mechanism is the CpG dinucleotide reduction observed in many single-stranded RNA 35 fraction of the observed C>U changes represent multiple, independent events ( Figure S3 ). CpG Dinucleotides in SARS-CoV-2 Extreme genomic CpG deficiency in SARS-CoV-2 and evasion of host 396 antiviral defense Multi-site co-398 mutations and 5''UTR CpG immunity escape drive the evolution of SARS-CoV-2 abstract: RNA viruses use CpG reduction to evade the host cell defense, but the driving mechanisms are still largely unknown. In an attempt to address this we used a rapidly growing genomic dataset of SARS-CoV-2 with relevant metadata information. Remarkably, by simply ordering SARS-CoV-2 genomes by their date of collection, we find a progressive increase of C-to-U substitutions resulting in 5’-UCG-3’ motif reduction that in turn have reduced the CpG frequency over just a few months of observation. This is consistent with APOBEC-mediated RNA editing resulting in CpG reduction, thus allowing the virus to escape ZAP-mediated RNA degradation. Our results thus link the dynamics of target sequences in the viral genome for two known host molecular defense mechanisms, mediated by the APOBEC and ZAP proteins. url: https://doi.org/10.1101/2020.06.19.161687 doi: 10.1101/2020.06.19.161687 id: cord-255755-5jccb3nh author: Saha, Sovan title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network date: 2020-04-23 words: 3668.0 sentences: 212.0 pages: flesch: 59.0 cache: ./cache/cord-255755-5jccb3nh.txt txt: ./txt/cord-255755-5jccb3nh.txt summary: title: Detection of spreader nodes and ranking of interacting edges in Human-SARS-CoV protein interaction network The new network attribute spreadability index along with generated SIS values of selected top spreader nodes when compared with the other network centrality based methodologies like Degree centrality (DC), Closeness centrality (CC), Local average centrality (LAC) and Betweeness centrality (BC) is found to perform relatively better than the existing-state-of-art. In the proposed methodology, Protein-protein interaction network (PPIN) has been used as the central component in identification of spreader nodes in SARS-CoV. Once it is formed, spreader nodes are identified in each of SARS-CoV proteins, its level 1 and level 2 of human network by the application of a new network attribute i.e. spreadability index which is a combination of three terminologies: 1) edge ratio [28] 2) neighborhood density [28] and 3) node weight [29] . abstract: The entire world has recently witnessed the commencement of coronavirus disease 19 (COVID-19) pandemic. It is caused by a novel coronavirus (n-CoV) generally distinguished as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). It has exploited human vulnerabilities to coronavirus outbreak. SARS-CoV-2 promotes fatal chronic respiratory disease followed by multiple organ failure which ultimately puts an end to human life. No proven vaccine for n-CoV is available till date in spite of significant research efforts worldwide. International Committee on Taxonomy of Viruses (ICTV) has reached to a consensus that the virus SARS-CoV-2 is highly genetically similar to Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) outbreak of 2003. It has been reported that SARS-CoV has ∼89% genetic similarities with n-CoV. With this hypothesis, the current work focuses on the identification of spreader nodes in SARS-CoV protein interaction network. Various network characteristics like edge ratio, neighborhood density and node weight have been explored for defining a new feature spreadability index by virtue of which spreader nodes and edges are identified. The selected top spreader nodes having high spreadability index have been also validated by Susceptible-Infected-Susceptible (SIS) disease model. Initially, the proposed method is applied on a synthetic protein interaction network followed by SARS-CoV-human protein interaction network. Hence, key spreader nodes and edges (ranked edges) are unmasked in SARS-CoV proteins and its connected level 1 and level 2 human proteins. The new network attribute spreadability index along with generated SIS values of selected top spreader nodes when compared with the other network centrality based methodologies like Degree centrality (DC), Closeness centrality (CC), Local average centrality (LAC) and Betweeness centrality (BC) is found to perform relatively better than the existing-state-of-art. url: https://doi.org/10.1101/2020.04.12.038216 doi: 10.1101/2020.04.12.038216 id: cord-315702-pn8247j2 author: Sahakijpijarn, Sawittree title: Development of Remdesivir as a Dry Powder for Inhalation by Thin Film Freezing date: 2020-09-22 words: 2300.0 sentences: 139.0 pages: flesch: 48.0 cache: ./cache/cord-315702-pn8247j2.txt txt: ./txt/cord-315702-pn8247j2.txt summary: Remdesivir exhibits in vitro activity against SARS-CoV-2 and was granted approval for Emergency Use. To maximize delivery to the lungs, we formulated remdesivir as a dry powder for inhalation using thin film freezing (TFF). In conclusion, TFF technology produces high potency remdesivir dry powder formulations for inhalation suitable to treat patients with COVID-19 on an outpatient basis and earlier in the disease course where effective antiviral therapy can reduce related morbidity and mortality. Although several techniques have been used to prepare inhalable powders, including 116 mechanical milling and spray drying, the advantages of thin film freezing (TFF) over other techniques 5 of 39 rely on the ability to produce aerosolizable particles composed of brittle matrix, nanostructured 118 aggregates. This shows that the 530 TFF technology can be used to minimize the need of excipient(s) in the formulation, thus maximizing 531 the amount of remdesivir being delivered to the lungs by dry powder inhalation. abstract: Remdesivir exhibits in vitro activity against SARS-CoV-2 and was granted approval for Emergency Use. To maximize delivery to the lungs, we formulated remdesivir as a dry powder for inhalation using thin film freezing (TFF). TFF produces brittle matrix nanostructured aggregates that are sheared into respirable low-density microparticles upon aerosolization from a passive dry powder inhaler. In vitro aerodynamic testing demonstrated that drug loading and excipient type affected the aerosol performance of remdesivir. Remdesivir combined with optimal excipients exhibited desirable aerosol performance (up to 93.0% FPF; 0.82μm MMAD). Remdesivir was amorphous after the TFF process, which benefitted drug dissolution in simulated lung fluid. TFF remdesivir formulations are stable after one-month storage at 25 °C/60%RH. In vivo pharmacokinetic evaluation showed that TFF-remdesivir-leucine was poorly absorbed into systemic circulation while TFF-remdesivir-Captisol® demonstrated increased systemic uptake compared to leucine. Remdesivir was hydrolyzed to the nucleoside analog GS-441524 in lung, and levels of GS-441524 were greater in lung with the leucine formulation compared to Captisol®. In conclusion, TFF technology produces high potency remdesivir dry powder formulations for inhalation suitable to treat patients with COVID-19 on an outpatient basis and earlier in the disease course where effective antiviral therapy can reduce related morbidity and mortality. url: https://doi.org/10.1101/2020.07.26.222109 doi: 10.1101/2020.07.26.222109 id: cord-335652-v98gv5uf author: Salazar, Cecilia title: Multiple introductions, regional spread and local differentiation during the first week of COVID-19 epidemic in Montevideo, Uruguay date: 2020-05-10 words: 2063.0 sentences: 131.0 pages: flesch: 48.0 cache: ./cache/cord-335652-v98gv5uf.txt txt: ./txt/cord-335652-v98gv5uf.txt summary: Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. This global health emergency has deployed international efforts to apply genomic epidemiology to track the spread of SARS-CoV-2 in real time. The recent development of targeted sequencing protocols by the ARTIC Network [3] , open sharing of genomic data through the GISAID (www.gisaid.org) database and straightforward bioinformatic tools for viral phylogenomics [4] , provides the opportunity to reconstruct global spatio-temporal dynamics of the COVID-19 pandemic with unprecedented comprehensiveness and resolution. We therefore aimed to characterize the spatio-temporal dynamics of SARS-CoV-2 by sequencing around 10% of cases occurred during the first week of outbreak in Montevideo, allowing us to identify transmission patterns, geographic origins and genetic variation among local strains. abstract: Background After its emergence in China in December 2019, the new coronavirus disease (COVID-19) caused by SARS-CoV-2, has rapidly spread infecting more than 3 million people worldwide. South America is among the last regions hit by COVID-19 pandemic. In Uruguay, first cases were detected on March 13 th 2020 presumably imported by travelers returning from Europe. Methods We performed whole-genome sequencing of 10 SARS-CoV-2 from patients diagnosed during the first week (March 16th to 19th) of COVID-19 outbreak in Uruguay. Then, we applied genomic epidemiology using a global dataset to reconstruct the local spatio-temporal dynamics of SARS-CoV-2. Results Our phylogeographic analysis showed three independent introductions of SARS-CoV-2 from different continents. Also, we evidenced regional circulation of viral strains originally detected in Spain. Introduction of SARS-CoV-2 in Uruguay could date back as early as Feb 20th. Identification of specific mutations showed rapid local genetic differentiation. Conclusions We evidenced early independent introductions of SARS-CoV-2 that likely occurred before first cases were detected. Our analysis set the bases for future genomic epidemiology studies to understand the dynamics of SARS-CoV-2 in Uruguay and the Latin America and the Caribbean region. url: https://doi.org/10.1101/2020.05.09.086223 doi: 10.1101/2020.05.09.086223 id: cord-338543-q6cl5kjp author: Salguero, Francisco J. title: Comparison of Rhesus and Cynomolgus macaques as an authentic model for COVID-19 date: 2020-09-17 words: 1093.0 sentences: 59.0 pages: flesch: 56.0 cache: ./cache/cord-338543-q6cl5kjp.txt txt: ./txt/cord-338543-q6cl5kjp.txt summary: Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques, resembling the mild clinical cases of COVID-19 in humans. In contrast to prior publications, in which rhesus are accepted to be the optimal study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of novel and repurposed interventions against SARS-CoV-2. Throat swabs from cynomolgus macaques contained 147 higher levels of viral RNA early in infection (one to three dpc) and remained ≥4.5 x 148 10 4 copies/ml for all animals between four and nine dpc. However viral RNA 159 levels above the LLOQ were detected at both three dpc and five dpc in cynomolgus 160 macaques in comparison to two dpc and three dpc in rhesus macaques ( Figure 2D ). abstract: A novel coronavirus, SARS-CoV-2, has been identified as the causative agent of the current COVID-19 pandemic. Animal models, and in particular non-human primates, are essential to understand the pathogenesis of emerging diseases and to the safety and efficacy of novel vaccines and therapeutics. Here, we show that SARS-CoV-2 replicates in the upper and lower respiratory tract and causes pulmonary lesions in both rhesus and cynomolgus macaques, resembling the mild clinical cases of COVID-19 in humans. Immune responses against SARS-CoV-2 were also similar in both species and equivalent to those reported in milder infections and convalescent human patients. Importantly, we have devised a new method for lung histopathology scoring that will provide a metric to enable clearer decision making for this key endpoint. In contrast to prior publications, in which rhesus are accepted to be the optimal study species, we provide convincing evidence that both macaque species authentically represent mild to moderate forms of COVID-19 observed in the majority of the human population and both species should be used to evaluate the safety and efficacy of novel and repurposed interventions against SARS-CoV-2. Accessing cynomolgus macaques will greatly alleviate the pressures on current rhesus stocks. url: https://doi.org/10.1101/2020.09.17.301093 doi: 10.1101/2020.09.17.301093 id: cord-346299-2s9j01q7 author: Salim Khan, S Muhammad title: Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study date: 2020-09-04 words: 1407.0 sentences: 102.0 pages: flesch: 55.0 cache: ./cache/cord-346299-2s9j01q7.txt txt: ./txt/cord-346299-2s9j01q7.txt summary: title: Seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar, northern India – a cross-sectional study Background Prevalence of IgG antibodies against SARS-CoV-2 infection provides essential information for deciding disease prevention and mitigation measures. We estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar. 65 Besides, assuming that antibodies provide partial or total immunity, seroprevalence surveys give Here, we present the results of a cross-sectional seroprevalence study in District Srinagar, 70 conducted between 1 st and 15 th July 2020, to estimate the prevalence of IgG antibodies against 71 SARS-CoV-2 among adults using a sensitive and specific chemiluminescent microparticle 72 immunoassay (CMIA)-based test. 156 We estimated the number of infections till two weeks before the study period, i.e., 15 th June 2020 157 to 30 th June 2020, by applying the age-and gender-specific seroprevalence rates found in the Table) . abstract: Background Prevalence of IgG antibodies against SARS-CoV-2 infection provides essential information for deciding disease prevention and mitigation measures. We estimate the seroprevalence of SARS-CoV-2 specific IgG antibodies in District Srinagar. Methods 2906 persons >18 years of age selected from hospital visitors across District Srinagar participated in the study. We tested samples for the presence of SARS-CoV-2 specific IgG antibodies using a chemiluminescent microparticle immunoassay-based serologic test. Results Age- and gender-standardized seroprevalence was 3.6% (95% CI 2.9% to 4.3%). Age 30-69 years, a recent history of symptoms of an influenza-like-illness, and a history of being placed under quarantine were significantly related to higher odds of the presence of SARS-CoV-2 specific IgG antibodies. The estimated number of SARS-CoV-2 infections during the two weeks preceding the study, adjusted for test performance, was 32602 with an estimated (median) infection-to-known-case ratio of 46 (95% CI 36 to 57). Conclusions The seroprevalence of SARS-CoV-2 specific IgG antibodies is low in the District. A large proportion of the population is still susceptible to the infection. A sizeable number of infections remain undetected, and a substantial proportion of people with symptoms compatible with COVID-19 are not tested. url: https://doi.org/10.1101/2020.09.04.282640 doi: 10.1101/2020.09.04.282640 id: cord-102920-z5q3wo7v author: Sang, Eric R. title: Integrate Structural Analysis, Isoform Diversity, and Interferon-Inductive Propensity of ACE2 to Refine SARS-CoV2 Susceptibility Prediction in Vertebrates date: 2020-06-28 words: 6437.0 sentences: 316.0 pages: flesch: 44.0 cache: ./cache/cord-102920-z5q3wo7v.txt txt: ./txt/cord-102920-z5q3wo7v.txt summary: Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad SARS-CoV2 susceptibility in wild and particularly domestic animals. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Along with showing a broad susceptibility potential across mammalian species based on structural analysis [26] [27] [28] , our results further reveal that domestic animals including dogs, pigs, cattle and goats may evolve previously unexamined immunogenetic diversity to restrict SARS-CoV2 infections. In addition to structural analysis of simulated S-RBD-ACE2 interaction, we propose that several immunogenetic factors, including the evolution of S-binding-void ACE2 isoforms in some domestic animals, the species-specific IFN system, and epigenetic regulation of IFN-stimulated property of host ACE2 genes, contribute to the viral susceptibility and the development of COVID-19-like symptoms in certain animal species [15, 38, 39, 49] . abstract: The current new coronavirus disease (COVID-19) has caused globally near 0.4/6 million confirmed deaths/infected cases across more than 200 countries. As the etiological coronavirus (a.k.a. SARS-CoV2) may putatively have a bat origin, our understanding about its intermediate reservoir between bats and humans, especially its tropism in wild and domestic animals, are mostly unknown. This constitutes major concerns in public health for the current pandemics and potential zoonosis. Previous reports using structural analysis of the viral spike protein (S) binding its cell receptor of angiotensin-converting enzyme 2 (ACE2), indicate a broad SARS-CoV2 susceptibility in wild and particularly domestic animals. Through integration of key immunogenetic factors, including the existence of S-binding-void ACE2 isoforms and the disparity of ACE2 expression upon early innate immune response, we further refine the SARS-CoV2 susceptibility prediction to fit recent experimental validation. In addition to showing a broad susceptibility potential across mammalian species based on structural analysis, our results also reveal that domestic animals including dogs, pigs, cattle and goats may evolve ACE2-related immunogenetic diversity to restrict SARS-CoV2 infections. Thus, we propose that domestic animals may be unlikely to play a role as amplifying hosts unless the virus has further species-specific adaptation. These findings may relieve relevant public concerns regarding COVID-19-like risk in domestic animals, highlight virus-host coevolution, and evoke disease intervention through targeting ACE2 molecular diversity and interferon optimization. url: https://doi.org/10.1101/2020.06.27.174961 doi: 10.1101/2020.06.27.174961 id: cord-348159-v5hrcl5k author: Sang, Eric R. title: Epigenetic Evolution of ACE2 and IL-6 Genes as Non-Canonical Interferon-Stimulated Genes Correlate to COVID-19 Susceptibility in Vertebrates date: 2020-09-10 words: 2076.0 sentences: 117.0 pages: flesch: 45.0 cache: ./cache/cord-348159-v5hrcl5k.txt txt: ./txt/cord-348159-v5hrcl5k.txt summary: Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. Third, we found that the evolutionary increase of 147 ACE2, and especially the IL-6 genes response to inflammatory and IFN signaling may 148 serve as epigenetic marker for COVID-19 susceptibility in some animal species including 149 humans. . This shows that ACE2 and especially IL-6 genes from CoV2(+) species contain CREs with significantly higher mPWM scores, indicating that in some vertebrate species, non-ISGs like ACE2 and especially IL-6 genes evolved to obtain high inductive propensity by inflammatory and IFN signaling, and may serve as epigenetic biomarkers (or triggers) for susceptibility prediction for COVID-19 and other ARD syndromes. abstract: Current novel coronavirus disease (COVID-19) has spread globally within a matter of months. The virus establishes a success in balancing its deadliness and contagiousness, and causes substantial differences in susceptibility and disease progression in people of different ages, genders and pre-existing comorbidities. Since these host factors are subjected to epigenetic regulation, relevant analyses on some key genes underlying COVID-19 pathogenesis were performed to longitudinally decipher their epigenetic correlation to COVID-19 susceptibility. The genes of host angiotensin-converting enzyme 2 (ACE2, as the major virus receptor) and interleukin (IL)-6 (a key immune-pathological factor triggering cytokine storm) were shown to evince active epigenetic evolution via histone modification and cis/trans-factors interaction across different vertebrate species. Extensive analyses revealed that ACE2 ad IL-6 genes are among a subset of non-canonical interferon-stimulated genes (non-ISGs), which have been designated recently for their unconventional responses to interferons (IFNs) and inflammatory stimuli through an epigenetic cascade. Furthermore, significantly higher positive histone modification markers and position weight matrix (PWM) scores of key cis-elements corresponding to inflammatory and IFN signaling, were discovered in both ACE2 and IL6 gene promoters across representative COVID-19-susceptible species compared to unsusceptible ones. Findings characterize ACE2 and IL-6 genes as non-ISGs that respond differently to inflammatory and IFN signaling from the canonical ISGs and their epigenetic properties may serve as biomarkers to longitudinally predict COVID-19 susceptibility in vertebrates and partially explain COVID-19 inequality in people of different subgroups. url: https://doi.org/10.1101/2020.09.09.273268 doi: 10.1101/2020.09.09.273268 id: cord-268795-tjmx6msm author: Sardar, Rahila title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis date: 2020-03-21 words: 2257.0 sentences: 128.0 pages: flesch: 47.0 cache: ./cache/cord-268795-tjmx6msm.txt txt: ./txt/cord-268795-tjmx6msm.txt summary: title: Comparative analyses of SAR-CoV2 genomes from different geographical locations and other coronavirus family genomes reveals unique features potentially consequential to host-virus interaction and pathogenesis We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Our analysis shows unique host-miRNAs targeting SARS-CoV2 virus genes. CELLO2GO (7)server was used to infer biological function for each protein of SARS-CoV2 genome with their localization prediction. Assembled SARS-CoV2 genomes sequences in FASTA format from India, USA, China, Italy and Nepal used for coronavirus typing tool analysis. For the phylogenetic analysis, we compared the sequences of 6 SARS-CoV2 isolates from different countries namely, Wuhan, India, Italy, USA and Nepal along with other corona virus species ( Figure 1 ). abstract: The ongoing pandemic of the coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2). We have performed an integrated sequence-based analysis of SARS-CoV2 genomes from different geographical locations in order to identify its unique features absent in SARS-CoV and other related coronavirus family genomes, conferring unique infection, facilitation of transmission, virulence and immunogenic features to the virus. The phylogeny of the genomes yields some interesting results. Systematic gene level mutational analysis of the genomes has enabled us to identify several unique features of the SARS-CoV2 genome, which includes a unique mutation in the spike surface glycoprotein (A930V (24351C>T)) in the Indian SARS-CoV2, absent in other strains studied here. We have also predicted the impact of the mutations in the spike glycoprotein function and stability, using computational approach. To gain further insights into host responses to viral infection, we predict that antiviral host-miRNAs may be controlling the viral pathogenesis. Our analysis reveals nine host miRNAs which can potentially target SARS-CoV2 genes. Interestingly, the nine miRNAs do not have targets in SARS and MERS genomes. Also, hsa-miR-27b is the only unique miRNA which has a target gene in the Indian SARS-CoV2 genome. We also predicted immune epitopes in the genomes url: https://doi.org/10.1101/2020.03.21.001586 doi: 10.1101/2020.03.21.001586 id: cord-323839-a4oejky0 author: Sasaki, Michihito title: SARS-CoV-2 variants with mutations at the S1/S2 cleavage site are generated in vitro during propagation in TMPRSS2-deficient cells date: 2020-08-28 words: 2100.0 sentences: 128.0 pages: flesch: 63.0 cache: ./cache/cord-323839-a4oejky0.txt txt: ./txt/cord-323839-a4oejky0.txt summary: These results indicated that S gene mutants are resistant to the 1 5 9 treatment with TMPRRSS2 inhibitors, but are sensitive to antivirals that target post entry In an effort to understand the selection mechanisms underlying the generation of these 1 6 4 mutant variants, we estimated the frequency of S gene mutants in virus population of 1 6 5 SARS-CoV-2 that had undergone serial passage in cultured cells. In contrast, nucleotide sequence 1 7 2 deletions around the S1/S2 cleavage site corresponding to del1 and del2 mutants were 1 7 3 observed in all three biological replicates of SARS-CoV-2 populations passaged in Vero 1 7 4 cells (Fig. 5a) . Moreover, we must be very objective when interpreting the results 2 3 0 from studies using Vero-passaged virus, especially those focused on S protein cleavage, Cells were infected with either WT or S mutants of SARS-CoV-2 at an MOI of 1. abstract: The spike (S) protein of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) binds to a host cell receptor which facilitates viral entry. A polybasic motif detected at the cleavage site of the S protein has been shown to broaden the cell tropism and transmissibility of the virus. Here we examine the properties of SARS-CoV-2 variants with mutations at the S protein cleavage site that undergo inefficient proteolytic cleavage. Virus variants with S gene mutations generated smaller plaques and exhibited a more limited range of cell tropism compared to the wild-type strain. These alterations were shown to result from their inability to utilize the entry pathway involving direct fusion mediated by the host type II transmembrane serine protease, TMPRSS2. Notably, viruses with S gene mutations emerged rapidly and became the dominant SARS-CoV-2 variants in TMPRSS2-deficient cells including Vero cells. Our study demonstrated that the S protein polybasic cleavage motif is a critical factor underlying SARS-CoV-2 entry and cell tropism. As such, researchers should be alert to the possibility of de novo S gene mutations emerging in tissue-culture propagated virus strains. url: https://doi.org/10.1101/2020.08.28.271163 doi: 10.1101/2020.08.28.271163 id: cord-104169-2sbc1guz author: Satish, Swarup title: The impact of preprint servers in the formation of novel ideas date: 2020-10-08 words: 4803.0 sentences: 306.0 pages: flesch: 59.0 cache: ./cache/cord-104169-2sbc1guz.txt txt: ./txt/cord-104169-2sbc1guz.txt summary: Our proposed Bayesian Approach to Novelty Detection (BAND) finds the time interval τ that maximizes the observed series of publication frequency for a phrase (Figure 1 ). Our motivation for finding τ using BAND is to compare the impact of different publication venues (i.e. preprint servers and peer-reviewed journals) that cover overlapping research topics. In our analysis (Section 5.2), we compare these methods to BAND not only for finding the first clear inflection point, but also how relevant τ is for the end goal of novelty detection and comparing research impact. • Can we find the point τ in time when a phrase is determined novel using our Bayesian Approach to Novelty Detection (BAND)? Our findings indicate that novel phrases, which we use as a proxy for new ideas, in most cases appear on pre-print servers and in peer reviewed journals. abstract: We study whether novel ideas in biomedical literature appear first in preprints or traditional journals. We develop a Bayesian method to estimate the time of appearance for a phrase in the literature, and apply it to a number of phrases, both automatically extracted and suggested by experts. We see that presently most phrases appear first in the traditional journals, but there is a number of phrases with the first appearance on preprint servers. A comparison of the general composition of texts from bioRxiv and traditional journals shows a growing trend of bioRxiv being predictive of traditional journals. We discuss the application of the method for related problems. url: https://doi.org/10.1101/2020.10.08.330696 doi: 10.1101/2020.10.08.330696 id: cord-310752-zl2g9wqo author: Sato, Taku title: Expression of ACE2 and TMPRSS2 proteins in the upper and lower aerodigestive tracts of rats date: 2020-05-15 words: 2135.0 sentences: 119.0 pages: flesch: 48.0 cache: ./cache/cord-310752-zl2g9wqo.txt txt: ./txt/cord-310752-zl2g9wqo.txt summary: Methods To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry. Results Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Notably, strong co-expression of ACE2 and TMPRSS2 proteins was observed in the taste buds of the tongue, nasal respiratory epithelium, trachea, bronchioles, alveoli, and the kidney. The strong co-expression of ACE2 and TMPRSS2 in the taste buds may explain the high incidence of ageusia or dysgeusia in patients with SARS-CoV-2 infection. Unlike that in the nasal respiratory epithelium, TMPRSS2 was more strongly expressed in the cytoplasm of tracheal epithelium, hence suggesting the trachea to be more prone to developing clinical symptoms after SARS-CoV-2 infection than the nasal tissue. abstract: Objective Patients with coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), exhibit not only respiratory symptoms but also symptoms of chemo-sensitive disorders and kidney failure. Cellular entry of SARS-CoV-2 depends on the binding of its spike protein to a cellular receptor named angiotensin-converting enzyme 2 (ACE2), and the subsequent spike protein-priming by host cell proteases, including transmembrane protease serine 2 (TMPRSS2). Thus, high expression of ACE2 and TMPRSS2 are considered to enhance the invading capacity of SARS-CoV-2. Methods To elucidate the underlying histological mechanisms of the aerodigestive disorders caused by SARS-CoV-2, we investigated the expression of ACE2 and TMPRSS2 proteins in the aerodigestive tracts of the tongue, hard palate with partial nasal tissue, larynx with hypopharynx, trachea, esophagus, lung, and kidney of rats through immunohistochemistry. Results Strong co-expression of ACE2 and TMPRSS2 proteins was observed in the nasal respiratory epithelium, trachea, bronchioles, alveoli, kidney, and taste buds of the tongue. Remarkably, TMPRSS2 expression was much stronger in the peripheral alveoli than in the central alveoli. These results coincide with the reported clinical symptoms of COVID-19, such as the loss of taste, loss of olfaction, respiratory dysfunction, and acute nephropathy. Conclusions A wide range of organs have been speculated to be affected by SARS-CoV-2 depending on the expression levels of ACE2 and TMPRSS2. Differential distribution of TMPRSS2 in the lung indicated the COVID-19 symptoms to possibly be exacerbated by TMPRSS2 expression. This study might provide potential clues for further investigation of the pathogenesis of COVID-19. Level of Evidence NA url: https://doi.org/10.1101/2020.05.14.097204 doi: 10.1101/2020.05.14.097204 id: cord-103421-46owvqw8 author: Saunders, Jaclyn K. title: METATRYP v 2.0: Metaproteomic Least Common Ancestor Analysis for Taxonomic Inference Using Specialized Sequence Assemblies - Standalone Software and Web Servers for Marine Microorganisms and Coronaviruses date: 2020-05-21 words: 5733.0 sentences: 237.0 pages: flesch: 37.0 cache: ./cache/cord-103421-46owvqw8.txt txt: ./txt/cord-103421-46owvqw8.txt summary: Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). This feature previously existed in METATRYP v 1 for generating peptide redundancy tables within the "Genome" sequencing data category and was used to show the relatively low occurrence of shared peptides across disparate taxa in the open ocean microbiome [1] . abstract: We present METATRYP version-2 software that identifies shared peptides across organisms within environmental metaproteomics studies to enable accurate taxonomic attribution of peptides during protein inference. Improvements include: ingestion of complex sequence assembly data categories (metagenomic and metatranscriptomic assemblies, single cell amplified genomes, and metagenome assembled genomes), prediction of the Least Common Ancestor (LCA) for a peptide shared across multiple organisms, increased performance through updates to the backend architecture, and development of a web portal (https://metatryp.whoi.edu). Major expansion of the marine database confirms low occurrence of shared tryptic peptides among disparate marine microorganisms, implying tractability for targeted metaproteomics. METATRYP was designed for ocean metaproteomics and has been integrated into the Ocean Protein Portal (https://oceanproteinportal.org); however, it can be readily applied to other domains. We describe the rapid deployment of a coronavirus-specific web portal (https://metatryp-coronavirus.whoi.edu/) to aid in use of proteomics on coronavirus research during the ongoing pandemic. A Coronavirus-focused METATRYP database identified potential SARS-CoV-2 peptide biomarkers and indicated very few shared tryptic peptides between SARS-CoV-2 and other disparate taxa, sharing 0.1% peptides or less (1 peptide) with the Influenza A & B pan-proteomes, establishing that taxonomic specificity is achievable using tryptic peptide-based proteomic diagnostic approaches. Statement of significance When assigning taxonomic attribution in bottom-up metaproteomics, the potential for shared tryptic peptides among organisms in mixed communities should be considered. The software program METATRYP v 2 and associated interactive web portals enables users to identify the frequency of shared tryptic peptides among taxonomic groups and evaluate the occurrence of specific tryptic peptides within complex communities. METATRYP facilitates phyloproteomic studies of taxonomic groups and supports the identification and evaluation of potential metaproteomic biomarkers. url: https://doi.org/10.1101/2020.05.20.107490 doi: 10.1101/2020.05.20.107490 id: cord-264296-0x90yubt author: Sawmya, Shashata title: Analyzing hCov genome sequences: Applying Machine Intelligence and beyond date: 2020-06-03 words: 5008.0 sentences: 312.0 pages: flesch: 60.0 cache: ./cache/cord-264296-0x90yubt.txt txt: ./txt/cord-264296-0x90yubt.txt summary: We present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. C. Several CNN-RNN based models are used to predict mutations at specific Sites of Interest (SoIs) of the sars-cov-2 genome sequence followed by further analyses of the same on several South-Asian countries. D. Overall, we present an analysis pipeline that can be further utilized as well as extended and revised (a) to study where a newly discovered genome sequence lies in relation to its predecessors in different regions of the world; (b) to analyse its virulence with respect to the number of deaths its predecessors have caused in their respective countries and (c) to analyse the mutation at specific important sites of the viral genome. abstract: Covid-19 pandemic, caused by the sars-cov-2 strain of coronavirus, has affected millions of people all over the world and taken thousands of lives. It is of utmost importance that the character of this deadly virus be studied and its nature be analysed. We present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. In a nutshell, we have prepared an analysis pipeline for hCov genome sequences leveraging the power of machine intelligence and uncovered what remained apparently shrouded by raw data. url: https://doi.org/10.1101/2020.06.03.131987 doi: 10.1101/2020.06.03.131987 id: cord-339431-kyr5lv15 author: Saçar Demirci, Müşerref Duygu title: Computational analysis of microRNA-mediated interactions in SARS-CoV-2 infection date: 2020-03-17 words: 2323.0 sentences: 163.0 pages: flesch: 52.0 cache: ./cache/cord-339431-kyr5lv15.txt txt: ./txt/cord-339431-kyr5lv15.txt summary: In the case of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA – based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Although there are studies regarding to the viral replication and their interaction with host innate immune system, the role of miRNA-mediated RNA-silencing in SARS-CoV-2 infection has not been enlightened yet. In this study, SARS-CoV-2 genome was searched for miRNA-like sequences and potential host-virus interactions based on miRNA actions were analyzed. In our study, we have also identified possible miRNA like small RNAs from SARS-CoV-2 genome which target important human genes. abstract: MicroRNAs (miRNAs) are post-transcriptional regulators of gene expression that have been found in more than 200 diverse organisms. Although it is still not fully established if RNA viruses could generate miRNAs that would target their own genes or alter the host gene expression, there are examples of miRNAs functioning as an antiviral defense mechanism. In the case of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there are several mechanisms that would make miRNAs impact the virus, like interfering with replication, translation and even modulating the host expression. In this study, we performed a machine learning based miRNA prediction analysis for the SARS-CoV-2 genome to identify miRNA-like hairpins and searched for potential miRNA – based interactions between the viral miRNAs and human genes and human miRNAs and viral genes. Our PANTHER gene function analysis results indicate that viral derived miRNA candidates could target various human genes involved in crucial cellular processes including transcription. For instance, a transcriptional regulator, STAT1 and transcription machinery might be targeted by virus-derived miRNAs. In addition, many known human miRNAs appear to be able to target viral genes. Considering the fact that miRNA-based therapies have been successful before, comprehending mode of actions of miRNAs and their possible roles during SARS-CoV-2 infections could create new opportunities for the development and improvement of new therapeutics. url: https://doi.org/10.1101/2020.03.15.992438 doi: 10.1101/2020.03.15.992438 id: cord-102505-g37ti2jj author: Schaworonkow, Natalie title: EEG-triggered TMS reveals stronger brain state-dependent modulation of motor evoked potentials at weaker stimulation intensities date: 2018-01-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Background Corticospinal excitability depends on the current brain state. The recent development of real-time EEG-triggered transcranial magnetic stimulation (EEG-TMS) allows studying this relationship in a causal fashion. Specifically, it has been shown that corticospinal excitability is higher during the scalp surface negative EEG peak compared to the positive peak of µ-oscillations in sensorimotor cortex, as indexed by larger motor evoked potentials (MEPs) for fixed stimulation intensity. Objective We further characterize the effect of µ-rhythm phase on the MEP input-output (IO) curve by measuring the degree of excitability modulation across a range of stimulation intensities. We furthermore seek to optimize stimulation parameters to enable discrimination of functionally relevant EEG-defined brain states. Methods A real-time EEG-TMS system was used to trigger MEPs during instantaneous brain-states corresponding to µ-rhythm surface positive and negative peaks with five different stimulation intensities covering an individually calibrated MEP IO curve in 15 healthy participants. Results MEP amplitude is modulated by µ-phase across a wide range of stimulation intensities, with larger MEPs at the surface negative peak. The largest relative MEP-modulation was observed for weak intensities, the largest absolute MEP-modulation for intermediate intensities. These results indicate a leftward shift of the MEP IO curve during the µ-rhythm negative peak. Conclusion The choice of stimulation intensity influences the observed degree of corticospinal excitability modulation by µ-phase. Lower stimulation intensities enable more efficient differentiation of EEG µ-phase-defined brain states. url: https://doi.org/10.1101/251363 doi: 10.1101/251363 id: cord-296649-h6oyjz56 author: Scherf-Clavel, Oliver title: Tissue Level Profiling of SARS-CoV-2 antivirals in mice to predict their effects: comparing Remdesivir’s active metabolite GS-441 524 vs. the clinically failed Hydroxychloroquine date: 2020-11-06 words: 5076.0 sentences: 263.0 pages: flesch: 53.0 cache: ./cache/cord-296649-h6oyjz56.txt txt: ./txt/cord-296649-h6oyjz56.txt summary: In this study, an adapted mouse model was chosen to demonstrate its suitability to provide sufficient information on the model substances GS-441 524 and HCQ regarding plasma concentration and distribution into relevant tissues a prerequisite for treatment effectiveness. Blood and organ samples were taken at several time points and drug concentrations were quantified in plasma and tissue homogenates by two liquid chromatography/tandem mass spectrometry methods. For GS-441 524, measured tissue concentrations exceeded the reported in vitro EC50 values by more than 10-fold and in consideration of its high efficacy against feline infectious peritonitis, GS-441 524 could indeed be effective against SARS-CoV-2 in vivo. The value obtained from our experiments falls in that range and is comparable to the V z obtained in mice from blood concentrations and to plasma V z measured in humans (see Table 4 ). abstract: Background and Objectives Remdesivir and hydroxychloroquine are or were among the most promising therapeutic options to tackle the current SARS-CoV-2 pandemic. Besides the use of the prodrug remdesivir itself, the direct administration of GS-441 524, the resulting main metabolite of remdesivir, could be advantageous and even more effective. All substances were not originally developed for the treatment of COVID-19 and especially for GS-441 524 little is known about its pharmacokinetic and physical-chemical properties. To justify the application of new or repurposed drugs in humans, pre-clinical in vivo animal models are mandatory to investigate relevant PK and PD properties and their relationship to each other. In this study, an adapted mouse model was chosen to demonstrate its suitability to provide sufficient information on the model substances GS-441 524 and HCQ regarding plasma concentration and distribution into relevant tissues a prerequisite for treatment effectiveness. Methods GS-441 524 and HCQ were administered intravenously as a single injection to male mice. Blood and organ samples were taken at several time points and drug concentrations were quantified in plasma and tissue homogenates by two liquid chromatography/tandem mass spectrometry methods. In vitro experiments were conducted to investigate the degradation of remdesivir in human plasma and blood. All pharmacokinetic analyses were performed with R Studio using non-compartmental analysis. Results High tissue to plasma ratios for GS-441 524 and HCQ were found, indicating a significant distribution into the examined tissue, except for the central nervous system and fat. For GS-441 524, measured tissue concentrations exceeded the reported in vitro EC50 values by more than 10-fold and in consideration of its high efficacy against feline infectious peritonitis, GS-441 524 could indeed be effective against SARS-CoV-2 in vivo. For HCQ, relatively high in vitro EC50 values are reported, which were not reached in all tissues. Facing its slow tissue distribution, HCQ might not lead to sufficient tissue saturation for a reliable antiviral effect. Conclusion The mouse model was able to characterise the PK and tissue distribution of both model substances and is a suitable tool to investigate early drug candidates against SARS-CoV-2. Furthermore, we could demonstrate a high tissue distribution of GS-441 524 even if not administered as the prodrug remdesivir. url: https://doi.org/10.1101/2020.09.16.299537 doi: 10.1101/2020.09.16.299537 id: cord-103465-6udhvl9n author: Schierding, William title: Low tolerance for transcriptional variation at cohesin genes is accompanied by functional links to disease-relevant pathways date: 2020-04-13 words: 6450.0 sentences: 323.0 pages: flesch: 41.0 cache: ./cache/cord-103465-6udhvl9n.txt txt: ./txt/cord-103465-6udhvl9n.txt summary: Results 140 genetic variants with regulatory potential are associated with cohesin loci Mitotic cohesin genes (SMC1A, SMC3, STAG1, STAG2, and RAD21), meiotic cohesin genes (SMC1B, STAG3, REC8, and RAD21L1), cohesin support genes (WAPL, NIPBL, PDS5A, PDS5B, and MAU2) and CTCF were investigated to determine if they contain non-coding genetic variants (SNPs) that make contact in 3D with genes and therefore could directly affect gene expression (GWAS-attributed and eQTL-attributed; Table 1, Table S1 ). Intriguingly, Haploreg motif prediction identified 16 of the 209 variants (7 different loci: MAU2, PDS5B, REC8, SMC1B, STAG3, RAD21L1, STAG1) as residing within protein binding domains associated with cohesin-related DNA interactions (i.e. RAD21, SMC3, and CTCF). Pathway enrichment implicates coordinated regulation of cohesin with essential cell cycle genes CoDeS3D identified 140 variants as being physically connected to, and associated with the expression levels of 310 genes (243 genes from eQTL-attributed variants, 141 from GWAS-attributed variants, and 74 overlap) across 6,795 significant tissue-specific regulatory connections (FDR p<0.05). abstract: Variants in DNA regulatory elements can alter the regulation of distant genes through spatial-regulatory connections. In humans, these spatial-regulatory connections are largely set during early development, when the cohesin complex plays an essential role in genome organisation and cell division. A full complement of the cohesin complex and its regulators is important for normal development, since heterozygous mutations in genes encoding these components are often sufficient to produce a disease phenotype. The implication that genes encoding the cohesin complex and cohesin regulators must be tightly controlled and resistant to variability in expression has not yet been formally tested. Here, we identify spatial-regulatory connections with potential to regulate expression of cohesin loci, including linking their expression to that of other genes. Connections that centre on the cohesin ring subunits (Mitotic: SMC1A, SMC3, STAG1, STAG2, RAD21/RAD21-AS; Meiotic: SMC1B, STAG3, REC8, RAD21L1), cohesin-ring support genes (NIPBL, MAU2, WAPL, PDS5A and PDS5B), and CTCF provide evidence of coordinated regulation that has little tolerance for perturbation. We identified transcriptional changes across a set of genes co-regulated with the cohesin loci that include biological pathways such as extracellular matrix production and proteasome-mediated protein degradation. Remarkably, many of the genes that are co-regulated with cohesin loci are themselves intolerant to loss-of-function. The results highlight the importance of robust regulation of cohesin genes, indicating novel pathways that may be important in the human cohesinopathy disorders. url: https://doi.org/10.1101/2020.04.11.037358 doi: 10.1101/2020.04.11.037358 id: cord-103112-m6cg67lz author: Schloer, Sebastian title: Targeting the endolysosomal host-SARS-CoV-2 interface by clinically licensed functional inhibitors of acid sphingomyelinase (FIASMA) including the antidepressant fluoxetine date: 2020-08-16 words: 1554.0 sentences: 91.0 pages: flesch: 51.0 cache: ./cache/cord-103112-m6cg67lz.txt txt: ./txt/cord-103112-m6cg67lz.txt summary: As the FIASMA group consists of a large number of small compounds that are well-tolerated and widely used for a broad range of clinical applications, exploring these licensed pharmaceuticals may offer a variety of promising antivirals for host-directed therapy to counteract enveloped viruses, including SARS-CoV-2 and COVID 19. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of 27 acid sphingomyelinase (FIASMA), efficiently inhibited the entry and propagation of SARS-CoV-28 2 in the cell culture model without cytotoxic effects and also exerted potent antiviral activity 29 against two currently circulating influenza A virus subtypes, an effect which was also observed 30 upon treatment with the FIASMAs amiodarone and imipramine. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of 27 acid sphingomyelinase (FIASMA), efficiently inhibited the entry and propagation of SARS-CoV-28 2 in the cell culture model without cytotoxic effects and also exerted potent antiviral activity 29 against two currently circulating influenza A virus subtypes, an effect which was also observed 30 upon treatment with the FIASMAs amiodarone and imipramine. abstract: The Corona Virus Disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Related Coronavirus 2 (SARS-CoV-2) is a global health emergency. As only very limited therapeutic options are clinically available, there is an urgent need for the rapid development of safe, effective, and globally available pharmaceuticals that inhibit SARS-CoV-2 entry and ameliorate COVID-19. In this study, we explored the use of small compounds acting on the homeostasis of the endolysosomal host-pathogen interface, to fight SARS-CoV-2 infection. We find that fluoxetine, a widely used antidepressant and a functional inhibitor of acid sphingomyelinase (FIASMA), efficiently inhibited the entry and propagation of SARS-CoV-2 in the cell culture model without cytotoxic effects and also exerted potent antiviral activity against two currently circulating influenza A virus subtypes, an effect which was also observed upon treatment with the FIASMAs amiodarone and imipramine. Mechanistically, fluoxetine induced both impaired endolysosomal acidification and the accumulation of cholesterol within the endosomes. As the FIASMA group consists of a large number of small compounds that are well-tolerated and widely used for a broad range of clinical applications, exploring these licensed pharmaceuticals may offer a variety of promising antivirals for host-directed therapy to counteract enveloped viruses, including SARS-CoV-2 and COVID 19. url: https://doi.org/10.1101/2020.07.27.222836 doi: 10.1101/2020.07.27.222836 id: cord-270329-t60t639i author: Schloer, Sebastian title: Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro date: 2020-10-16 words: 1053.0 sentences: 77.0 pages: flesch: 52.0 cache: ./cache/cord-270329-t60t639i.txt txt: ./txt/cord-270329-t60t639i.txt summary: title: Drug synergy of combinatory treatment with remdesivir and the repurposed drugs fluoxetine and itraconazole effectively impairs SARS-CoV-2 infection in vitro We tested the antiviral potential of repurposing the antifungal itraconazole and the antidepressant fluoxetine on the production of infectious SARS-CoV-2 particles in the polarized Calu-3 cell culture model and evaluated the added benefit of a combinatory use of these host-directed drugs with remdesivir, an inhibitor of viral RNA polymerase. Importantly, both itraconazole-remdesivir and fluoxetine-remdesivir combinations inhibited the production of infectious SARS-CoV-2 particles > 90% and displayed synergistic effects in commonly used reference models for drug interaction. While drugs 87 directly acting on virus structures are much more likely to completely eliminate the 88 pathogens in shorter treatment time, emerging viral resistance to these antivirals is a major 89 concern, as observed with the influenza neuraminidase inhibitor oseltamivir (Kim et al., itraconazole antiviral activity in SARS-CoV-2 infected Vero cells (Fig. 1b) . abstract: The SARS-COV-2 pandemic and the global spread of coronavirus disease 2019 (COVID-19) urgently calls for efficient and safe antiviral treatment strategies. A straightforward approach to speed up drug development at lower costs is drug repurposing. Here we investigated the therapeutic potential of targeting the host- SARS-CoV-2 interface via repurposing of clinically licensed drugs and evaluated their use in combinatory treatments with virus- and host-directed drugs. We tested the antiviral potential of repurposing the antifungal itraconazole and the antidepressant fluoxetine on the production of infectious SARS-CoV-2 particles in the polarized Calu-3 cell culture model and evaluated the added benefit of a combinatory use of these host-directed drugs with remdesivir, an inhibitor of viral RNA polymerase. Drug treatments were well-tolerated and potent impaired viral replication was observed with all drug treatments. Importantly, both itraconazole-remdesivir and fluoxetine-remdesivir combinations inhibited the production of infectious SARS-CoV-2 particles > 90% and displayed synergistic effects in commonly used reference models for drug interaction. Itraconazole-Remdesivir and Fluoxetine-Remdesivir combinations are promising therapeutic options to control SARS-CoV-2 infection and severe progression of COVID-19. url: https://doi.org/10.1101/2020.10.16.342410 doi: 10.1101/2020.10.16.342410 id: cord-355728-wivk0bm0 author: Schoof, Michael title: An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation date: 2020-08-17 words: 3613.0 sentences: 377.0 pages: flesch: 68.0 cache: ./cache/cord-355728-wivk0bm0.txt txt: ./txt/cord-355728-wivk0bm0.txt summary: Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Class I nanobodies emerged with highly 144 variable activity in this assay with Nb6 and Nb11 as two of the most potent clones with IC50 145 values of 370 and 540 nM, respectively (Table 1) To define the binding sites of Nb6 and Nb11, we determined their cryogenic electron 156 microscopy (cryo-EM) structures bound to Spike* ( Fig. 2A state RBDs only contacts a single RBD (Fig. 2D) . 277 278 mNb6-tri displays further gains in potency in both pseudovirus and live SARS-CoV-2 infection 279 assays with IC50 values of 120 pM (5.0 ng/mL) and 54 pM (2.3 ng/mL), respectively (Fig. 4H-I, 280 Table 1). abstract: Without an effective prophylactic solution, infections from SARS-CoV-2 continue to rise worldwide with devastating health and economic costs. SARS-CoV-2 gains entry into host cells via an interaction between its Spike protein and the host cell receptor angiotensin converting enzyme 2 (ACE2). Disruption of this interaction confers potent neutralization of viral entry, providing an avenue for vaccine design and for therapeutic antibodies. Here, we develop single-domain antibodies (nanobodies) that potently disrupt the interaction between the SARS-CoV-2 Spike and ACE2. By screening a yeast surface-displayed library of synthetic nanobody sequences, we identified a panel of nanobodies that bind to multiple epitopes on Spike and block ACE2 interaction via two distinct mechanisms. Cryogenic electron microscopy (cryo-EM) revealed that one exceptionally stable nanobody, Nb6, binds Spike in a fully inactive conformation with its receptor binding domains (RBDs) locked into their inaccessible down-state, incapable of binding ACE2. Affinity maturation and structure-guided design of multivalency yielded a trivalent nanobody, mNb6-tri, with femtomolar affinity for SARS-CoV-2 Spike and picomolar neutralization of SARS-CoV-2 infection. mNb6-tri retains stability and function after aerosolization, lyophilization, and heat treatment. These properties may enable aerosol-mediated delivery of this potent neutralizer directly to the airway epithelia, promising to yield a widely deployable, patient-friendly prophylactic and/or early infection therapeutic agent to stem the worst pandemic in a century. url: https://doi.org/10.1101/2020.08.08.238469 doi: 10.1101/2020.08.08.238469 id: cord-305589-ofpna4k1 author: Schubert, Katharina title: SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation date: 2020-07-07 words: 4090.0 sentences: 229.0 pages: flesch: 55.0 cache: ./cache/cord-305589-ofpna4k1.txt txt: ./txt/cord-305589-ofpna4k1.txt summary: By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. Based on these results we assembled in vitro a 40S-Nsp1 complex and determined its structure at 2.8 Å resolution using cryo-EM (Extended Data Fig. 2 ). As observed in the high-resolution structure of the 40S-Nsp1 complex, the C-terminal part of Nsp1 in the mRNA entrance channel (Fig. 1e ) folds into two helices that interact with h18 of the 18S rRNA as well as proteins uS3 in the head and uS5 and eS30 in the body, respectively ( Fig. 1f; Fig. 2a ). Our structural data suggest that SARS-CoV-2 Nsp1 inhibits translation by sterically occluding the entrance region of the mRNA channel and interfering with binding of cellular mRNAs (Fig. 4a,b) . abstract: The non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, is the first viral protein that is synthesized in SARS-CoV-2 infected human cells to suppress host innate immune functions1,2. By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. The protein inserts its C-terminal domain at the entrance to the mRNA channel where it interferes with mRNA binding. We observe potent translation inhibition in the presence of Nsp1 in lysates from human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5’ untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines inhibition of translation by Nsp1 with efficient translation of the viral mRNA to achieve expression of viral genes3. url: https://doi.org/10.1101/2020.07.07.191676 doi: 10.1101/2020.07.07.191676 id: cord-103813-w2sb6h94 author: Schumacher, Garrett J. title: Genetic information insecurity as state of the art date: 2020-07-10 words: 6459.0 sentences: 358.0 pages: flesch: 35.0 cache: ./cache/cord-103813-w2sb6h94.txt txt: ./txt/cord-103813-w2sb6h94.txt summary: Therefore, human genetic information is a uniquely confidential form of data that requires increased security controls and scrutiny. Sensitive genetic information, which includes both biological material and digital genetic data, is the primary asset of concern, and associated assets, such as metadata, electronic health records and intellectual property, are also vulnerable within this ecosystem. ❖ Private Sensitive Genetic Information can be expected to cause a moderate level of risk to a nation, ethnic group, individual, or stakeholder if it is disclosed, modified, or destroyed without authorization. The genetic information ecosystem is a distributed cyber-physical system containing numerous stakeholders (Supplementary Material, Appendix 1), personnel, and devices for computing and networking purposes. Genetic information security is a shared responsibility between sequencing laboratories and device vendors, as well as all other involved stakeholders. Examples include biorepositories, DNA sequencing laboratories, researchers, cloud and other service providers, and supply chain entities responsible for devices, software and materials. abstract: Genetic information is being generated at an increasingly rapid pace, offering advances in science and medicine that are paralleled only by the threats and risk present within the responsible ecosystem. Human genetic information is identifiable and contains sensitive information, but genetic data security is only recently gaining attention. Genetic data is generated in an evolving and distributed cyber-physical ecosystem, with multiple systems that handle data and multiple partners that utilize the data. This paper defines security classifications of genetic information and discusses the threats, vulnerabilities, and risk found throughout the entire genetic information ecosystem. Laboratory security was found to be especially challenging, primarily due to devices and protocols that were not designed with security in mind. Likewise, other industry standards and best practices threaten the security of the ecosystem. A breach or exposure anywhere in the ecosystem can compromise sensitive information. Extensive development will be required to realize the potential of this emerging field while protecting the bioeconomy and all of its stakeholders. url: https://doi.org/10.1101/2020.07.08.192666 doi: 10.1101/2020.07.08.192666 id: cord-103085-vf4qyvft author: Seitz, Christian title: Multiscale simulations examining glycan shield effects on drug binding to influenza neuraminidase date: 2020-11-02 words: 9735.0 sentences: 512.0 pages: flesch: 50.0 cache: ./cache/cord-103085-vf4qyvft.txt txt: ./txt/cord-103085-vf4qyvft.txt summary: Using Brownian dynamics simulations, we observe a twoto eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. We have utilized BD to estimate the rates of binding of small molecules to the primary (i.e. active/catalytic) and secondary (i.e. hemadsorption) binding sites of influenza neuraminidase in glycosylated and unglycosylated states. The protein-ligand atom pairs were taken from crystal structures of ligands in the primary and secondary sites of neuraminidase for each monomer, and simulations were run for the full tetramer. Keeping in mind the primary and secondary binding sites are located just beneath the glycans (Figure 1) , the size and flexibility of the glycans here shows that they have the capability to "shield" the binding sites from ligand association. (A) The glycan structures from the MD simulations show a moderate association rate inhibition to the primary binding site irrespective of ligand chosen. abstract: Influenza neuraminidase is an important drug target. Glycans are present on neuraminidase, and are generally considered to inhibit antibody binding via their glycan shield. In this work we studied the effect of glycans on the binding kinetics of antiviral drugs to the influenza neuraminidase. We created all-atom in silico systems of influenza neuraminidase with experimentally-derived glycoprofiles consisting of four systems with different glycan conformations and one system without glycans. Using Brownian dynamics simulations, we observe a two- to eight-fold decrease in the rate of ligand binding to the primary binding site of neuraminidase due to the presence of glycans. These glycans are capable of covering much of the surface area of neuraminidase, and the ligand binding inhibition is derived from glycans sterically occluding the primary binding site on a neighboring monomer. Our work also indicates that drugs preferentially bind to the primary binding site (i.e. the active site) over the secondary binding site, and we propose a binding mechanism illustrating this. These results help illuminate the complex interplay between glycans and ligand binding on the influenza membrane protein neuraminidase. Statement of Significance The influenza glycoprotein neuraminidase is the target for three FDA-approved influenza drugs in the US. However, drug resistance and low drug effectiveness merits further drug development towards neuraminidase, which is hindered by our limited understanding of glycan effects on ligand binding. Generally, drug developers do not include glycans in their development pipelines. Here, we show that even though glycans can reduce drug binding towards neuraminidase, we recommend future drug development work to focus on strong binders with a long lifetime. Furthermore, we examine the binding competition between the primary and secondary binding sites on neuraminidase, leading us to propose a new, to the best of our knowledge, multivalent binding mechanism. url: https://doi.org/10.1101/2020.08.12.248690 doi: 10.1101/2020.08.12.248690 id: cord-280922-w6a5ec06 author: Sen, Sanjana title: Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score date: 2020-10-29 words: 4134.0 sentences: 289.0 pages: flesch: 55.0 cache: ./cache/cord-280922-w6a5ec06.txt txt: ./txt/cord-280922-w6a5ec06.txt summary: Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. Furthermore, a recent review on antibody-dependent enhancement of SARS-CoV-2 stated, "At present, there are no known clinical findings, immunological assays or biomarkers that can differentiate any severe infection from immune-enhanced disease, whether by measuring antibodies, T cells or intrinsic host responses (7) ." This conclusion inspired our study. The results demonstrate that Abs to a specific epitope from N protein plus disease risk factors strongly correlate with COVID-19 disease severity. The DRFS of patients with αEp9 Abs strongly correlates with COVID-19 disease severity (Pearson''s r = 0.72, p-value <0.0001, and R 2 = 0.52) (Fig. 4A) . abstract: Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, ELISA and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide-range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the ICU, requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within six days post-symptom onset and sometimes within one day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 Likelihood Ratio (96.72% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. url: https://doi.org/10.1101/2020.10.15.341743 doi: 10.1101/2020.10.15.341743 id: cord-103306-1wc3f1rl author: Sengupta, Sourodip title: Matrix metalloproteinases and tissue inhibitors of metalloproteinases in murine coronavirus-induced neuroinflammation date: 2020-09-18 words: 3579.0 sentences: 229.0 pages: flesch: 53.0 cache: ./cache/cord-103306-1wc3f1rl.txt txt: ./txt/cord-103306-1wc3f1rl.txt summary: Elevated mRNA and protein levels of tissue inhibitors of metalloproteinases 1 (TIMP-1) in MHV-A59 infection are suggestive of a TIMP-1 mediated host antiviral response. Total RNA was isolated from mock and virus-infected brain tissues 238 for expression analysis of viral nucleocapsid and Mmp genes through RT-qPCR. MMPs. To understand the regulation of MMPs upon MHV-A59 infection, we also 254 considered the gene expression of TIMPs. As described above, total RNA from brain samples 255 of mock and MHV-A59 infected mice were subjected to RT-qPCR using specific primers 256 12 (Table 1) to determine the transcript levels of Timp1, Timp2, Timp3, and Timp4. While Timp1 mRNA 260 followed a similar expression pattern as the Mmps following MHV-A59 infection-induced 261 inflammation, its protein levels remained high throughout post-infection, as shown in the 262 representative figure (Fig. 2, B) . Transcript levels of Parkinson''s disease 7 312 (Park7) gene were significantly upregulated following RSA59 infection and remained 313 elevated p.i compared to mock-infected samples (Fig. 7, A; p<0.05). abstract: Mouse hepatitis virus (MHV) belongs to the same beta-coronavirus family as SARS-CoV-2, MERS-CoV, and SARS-CoV. Studies have shown the requirement of host cellular proteases for priming the surface spike protein during viral entry and transmission in coronaviruses. The metzincin family of metal-dependent endopeptidases called matrix metalloproteinases (MMPs) is involved in virus encephalitis, enhanced blood-brain barrier permeability, or cell-to-cell fusion upon viral infection. Here we show the role of MMPs as mediators of virus-induced host neuroinflammatory response in the MHV model. Infection of mice with wild-type MHV-A59 or its isogenic recombinant strains, RSA59 or RSMHV2 significantly upregulated MMP-3, MMP-8, and MMP-14 transcript levels. Functional network assessment with Ingenuity Pathway Analysis revealed a direct involvement of these MMPs in disrupting junctional assembly between endothelial cells via interaction with junctional adhesion molecules and thereby facilitating transmigration of peripheral lymphocytes. Our findings also suggest mRNA upregulation of Park7, which is involved in NADPH oxidase-dependent ROS production, following RSA59 infection. RSA59 infection resulted in elevated mRNA levels of RelA, a subunit of NF-κB. Infection with MHV-A59 is known to generate ROS, and oxidative stress can activate NF-κB. Thus, our findings indicate the existence of a possible nexus between ROS, NF-κB, and MMPs in RSA59-induced neuroinflammation. We also assessed the expression of endogenously produced regulators of MMP activities. Elevated mRNA and protein levels of tissue inhibitors of metalloproteinases 1 (TIMP-1) in MHV-A59 infection are suggestive of a TIMP-1 mediated host antiviral response. Importance The newly emergent coronavirus has brought the world to a near standstill. In the past, studies have focused on the function of host proteases in virus attachment and entry. Our research indicates the involvement of a group of metal-dependent host proteases in inflammation associated with coronavirus infection. Inflammation is the first response of the host to virus infection. While it helps in restricting the spread and clearance of viral particles, uncontrolled inflammation results in several inflammatory consequences. Therefore, it becomes vital to limit unchecked host immune response. The inhibition of specific metalloproteases represents a potential new therapeutic approach in coronavirus infection and disease outcome. url: https://doi.org/10.1101/2020.09.17.302877 doi: 10.1101/2020.09.17.302877 id: cord-102778-b1ul7zug author: Serrao, Juliet.M. title: Alfaxalone activates Human Pregnane-X Receptors with greater efficacy than Allopregnanolone: an in-vitro study with implications for neuroprotection during anesthesia date: 2020-09-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Background Alfaxalone is a fast acting intravenous anesthetic with high therapeutic index. It is an analogue of the naturally-occurring neurosteroid, allopregnanolone which has been implicated in causing neuroprotection, neurogenesis and preservation of cognition, through activation of pregnane X receptors in the central nervous system. This study investigated whether alfaxalone can activate human pregnane X receptors (h-PXR) as effectively as allopregnanolone. Methods Allopregnanolone and alfaxalone were dissolved in dimethyl sulfoxide to make allopregnanolone and alfaxalone treatment solutions (serial 3-fold dilution concentration range, 50,000 – 206 nM). Activation of h-PXR by these ligand solutions compared with vehicle control was measured by an in-vitro method using human embryonic kidney cells (HEK293) expressing h-PXR hybridised and linked to the firefly luciferase gene. Ligand binding with and activation of h-PXR in those cells caused downstream changes in luciferase activity and light emission. That activity was measured as relative light units using a plate-reading luminometer, thus quantifying the changes in h-PXR activity caused by the ligand applied to the HEK293 cells. Ligand log concentration response curves were constructed to compare efficacy and potency of allopregnanolone and alfaxalone. Results Allopregnanolone and alfaxalone both activated the h-PXR to cause dose-related light emission by the linked firefly luciferase. Control solutions (0.1% dimethyl sulfoxide) produced low level light emissions. Equimolar concentrations of alfaxalone were more efficacious in activation of h-PXR: 50,000 nM, p = 0.0019; 16,700 nM, p = 0.0472; 5,600 nM, p = 0.0031 [Brown-Forsythe and Welch ANOVA]. Conclusions Alfaxalone activates human-pregnane X receptors with greater efficacy compared with the endogenous ligand allopregnanolone. These results suggest that alfaxalone sedation and anesthesia may be accompanied by beneficial effects normally caused by the physiological effects of allopregnanolone, namely neuroprotection, neurogenesis, and preservation of cognition. url: https://doi.org/10.1101/2020.09.05.284075 doi: 10.1101/2020.09.05.284075 id: cord-102206-mb0qcd0b author: Seymour, Elif title: Configurable Digital Virus Counter on Robust Universal DNA Chips date: 2020-10-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Here, we demonstrate real-time multiplexed virus detection by applying DNA-directed antibody immobilization technique to a single-particle interferometric reflectance imaging sensor (SP-IRIS). In this technique, the biosensor chip surface spotted with different DNA sequences is converted to a multiplexed antibody array by flowing antibody-DNA conjugates and allowing specific DNA-DNA hybridization. The resulting antibody array is shown to detect three different recombinant Vesicular Stomatitis Viruses (rVSVs) genetically engineered to express surface glycoproteins of Ebola, Marburg, and Lassa viruses in real-time in a disposable microfluidic cartridge. We also show that this method can be modified to produce a single-step, homogeneous assay format by mixing the antibody-DNA conjugates with the virus sample in solution phase prior to flowing in the microfluidic cartridge, eliminating the antibody immobilization step. This homogenous approach achieved detection of the model Ebola virus, rVSV-EBOV, at a concentration of 100 PFU/ml in 1 hour. Finally, we demonstrate the feasibility of this homogeneous technique as a rapid test using a passive microfluidic cartridge. A concentration of 104 PFU/ml was detectable under 10 minutes for the rVSV-Ebola virus. Utilizing DNA microarrays for antibody-based diagnostics is an alternative approach to antibody microarrays and offers advantages such as configurable sensor surface, long-term storage ability, and decreased antibody use. We believe these properties will make SP-IRIS a versatile and robust platform for point-of-care diagnostics applications. url: https://doi.org/10.1101/2020.10.22.350579 doi: 10.1101/2020.10.22.350579 id: cord-350558-qfdp4ov9 author: Shaban, Mohammed Samer title: Inhibiting coronavirus replication in cultured cells by chemical ER stress date: 2020-08-26 words: 5077.0 sentences: 297.0 pages: flesch: 58.0 cache: ./cache/cord-350558-qfdp4ov9.txt txt: ./txt/cord-350558-qfdp4ov9.txt summary: We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. A detailed proteomics analysis reveals multiple thapsigargin-78 regulated pathways and a network of proteins that are suppressed by CoV but (re)activated by 79 chemically stressed infected cells. we determined the expression levels of 166 components of the ER stress pathway KEGG 04141 85 "protein processing in endoplasmic reticulum" in human HuH7 liver cells, a commonly used cellular 86 model for CoV replication, in response to infections with HCoV-229E and MERS-CoV, respectively. The highly inducible HERPUD1 protein has an essential scaffolding function for the organization of searching our proteomics data for further ERAD factors we were able to retrieve a total of 34 (for 284 MERS-CoV) and 20 (for SARS-CoV-2) proteins of the canonical ERQC and ERAD pathways for 285 which a differential expression was observed in virus-infected cells treated with thapsigargin (Fig. 286 5H) . abstract: Coronaviruses (CoVs) are important human pathogens for which no specific treatment is available. Here, we provide evidence that pharmacological reprogramming of ER stress pathways can be exploited to suppress CoV replication. We found that the ER stress inducer thapsigargin efficiently inhibits coronavirus (HCoV-229E, MERS-CoV, SARS-CoV-2) replication in different cell types, (partially) restores the virus-induced translational shut-down, and counteracts the CoV-mediated downregulation of IRE1α and the ER chaperone BiP. Proteome-wide data sets revealed specific pathways, protein networks and components that likely mediate the thapsigargin-induced antiviral state, including HERPUD1, an essential factor of ER quality control, and ER-associated protein degradation complexes. The data show that thapsigargin hits a central mechanism required for CoV replication, suggesting that thapsigargin (or derivatives thereof) may be developed into broad-spectrum anti-CoV drugs. One Sentence Summary / Running title Suppression of coronavirus replication through thapsigargin-regulated ER stress, ERQC / ERAD and metabolic pathways url: https://doi.org/10.1101/2020.08.26.266304 doi: 10.1101/2020.08.26.266304 id: cord-324480-7u5lh4jx author: Sharma, A. title: Structural stability of SARS-CoV-2 degrades with temperature date: 2020-10-14 words: 1541.0 sentences: 88.0 pages: flesch: 51.0 cache: ./cache/cord-324480-7u5lh4jx.txt txt: ./txt/cord-324480-7u5lh4jx.txt summary: Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. However an understanding of how SARS-CoV-2 survives different environmental conditions is still incomplete and mechanisms of virus particle degradation are poorly mapped out. A key challenge in studying SARS-CoV-2 is the extreme level of threat associated with the live virus and the resultant need for high safety standards for such work. Here we used this technology to study the stability of the viral envelope and associated proteins (M, E, and S) under different environmental conditions. Environmental stability of SARS-CoV-2 on different types of surfaces under indoor and seasonal climate conditions abstract: SARS-CoV-2 is a novel coronavirus which has caused the COVID-19 pandemic. Other known coronaviruses show a strong pattern of seasonality, with the infection cases in humans being more prominent in winter. Although several plausible origins of such seasonal variability have been proposed, its mechanism is unclear. SARS-CoV-2 is transmitted via airborne droplets ejected from the upper respiratory tract of the infected individuals. It has been reported that SARS-CoV-2 can remain infectious for hours on surfaces. As such, the stability of viral particles both in liquid droplets as well as dried on surfaces is essential for infectivity. Here we have used atomic force microscopy to examine the structural stability of individual SARS-CoV-2 virus like particles at different temperatures. We demonstrate that even a mild temperature increase, commensurate with what is common for summer warming, leads to dramatic disruption of viral structural stability, especially when the heat is applied in the dry state. This is consistent with other existing non-mechanistic studies of viral infectivity, provides a single particle perspective on viral seasonality, and strengthens the case for a resurgence of COVID-19 in winter. Statement of Scientific Significance The economic and public health impact of the COVID-19 pandemic are very significant. However scientific information needed to underpin policy decisions are limited partly due to novelty of the SARS-CoV-2 pathogen. There is therefore an urgent need for mechanistic studies of both COVID-19 disease and the SARS-CoV-2 virus. We show that individual virus particles suffer structural destabilization at relatively mild but elevated temperatures. Our nanoscale results are consistent with recent observations at larger scales. Our work strengthens the case for COVID-19 resurgence in winter. url: https://doi.org/10.1101/2020.10.12.336818 doi: 10.1101/2020.10.12.336818 id: cord-103523-46hn2249 author: Shaw, Dario R. title: Extracellular electron transfer-dependent anaerobic oxidation of ammonium by anammox bacteria date: 2019-11-26 words: 3315.0 sentences: 202.0 pages: flesch: 52.0 cache: ./cache/cord-103523-46hn2249.txt txt: ./txt/cord-103523-46hn2249.txt summary: Here we show using complementary approaches that in the absence of NO2−, freshwater and marine anammox bacteria couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). However, it is still unknown whether anammox bacteria have EET 27 capability and can couple the oxidation of NH4 + with transfer of electrons to carbon-based 28 insoluble extracellular electron acceptors. However, it is still unknown whether anammox bacteria have EET 27 capability and can couple the oxidation of NH4 + with transfer of electrons to carbon-based 28 insoluble extracellular electron acceptors. Here we show using complementary approaches that in 29 the absence of NO2 -, freshwater and marine anammox bacteria couple the oxidation of NH4 + with 30 transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene 31 oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). abstract: Anaerobic ammonium oxidation (anammox) by anammox bacteria contributes significantly to the global nitrogen cycle, and plays a major role in sustainable wastewater treatment. Anammox bacteria convert ammonium (NH4+) to dinitrogen gas (N2) using nitrite (NO2−) or nitric oxide (NO) as the electron acceptor. In the absence of NO2− or NO, anammox bacteria can couple formate oxidation to the reduction of metal oxides such as Fe(III) or Mn(IV). Their genomes contain homologs of Geobacter and Shewanella cytochromes involved in extracellular electron transfer (EET). However, it is still unknown whether anammox bacteria have EET capability and can couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors. Here we show using complementary approaches that in the absence of NO2−, freshwater and marine anammox bacteria couple the oxidation of NH4+ with transfer of electrons to carbon-based insoluble extracellular electron acceptors such as graphene oxide (GO) or electrodes poised at a certain potential in microbial electrolysis cells (MECs). Metagenomics, fluorescence in-situ hybridization and electrochemical analyses coupled with MEC performance confirmed that anammox electrode biofilms were responsible for current generation through EET-dependent oxidation of NH4+. 15N-labelling experiments revealed the molecular mechanism of the EET-dependent anammox process. NH4+ was oxidized to N2 via hydroxylamine (NH2OH) as intermediate when electrode was the terminal electron acceptor. Comparative transcriptomics analysis supported isotope labelling experiments and revealed an alternative pathway for NH4+ oxidation coupled to EET when electrode is used as electron acceptor compared to NO2−as electron acceptor. To our knowledge, our results provide the first experimental evidence that marine and freshwater anammox bacteria can couple NH4+ oxidation with EET, which is a significant finding, and challenges our perception of a key player of anaerobic oxidation of NH4+ in natural environments and engineered systems. url: https://doi.org/10.1101/855817 doi: 10.1101/855817 id: cord-102358-kf04tra6 author: Sheffield, Lakbira title: Age-dependent impairment of disease tolerance is associated with a robust transcriptional response following RNA virus infection in Drosophila date: 2020-09-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Advanced age in humans is associated with greater susceptibility to and higher mortality rates from infections, including infections with some RNA viruses. The underlying innate immune mechanisms, which represent the first line of defense against pathogens, remain incompletely understood. Drosophila melanogaster is able to mount potent and evolutionarily conserved innate immune defenses against a variety of microorganisms including viruses and serves as an excellent model organism for studying host-pathogen interactions. With its relatively short lifespan, Drosophila also is an organism of choice for aging studies. Despite numerous advantages that this model offers, Drosophila has not been used to its potential to investigate the response of the aged host to viral infection. Here we show that in comparison to younger flies, aged Drosophila succumb more rapidly to infection with the RNA-containing Flock House Virus (FHV) due to an age-dependent defect in disease tolerance. In comparison to younger individuals, we find that older Drosophila mount larger transcriptional responses characterized by differential regulation of more genes and genes regulated to a greater extent. Our results indicate that loss of disease tolerance to FHV with age possibly results from a stronger regulation of genes involved in apoptosis, activation of the Drosophila Immune deficiency (IMD) NF-kB pathway or from downregulation of genes whose products function in mitochondria and mitochondrial respiration. Our work shows that Drosophila can serve as a model to investigate host-virus interactions during aging and sets the stage for future analysis of the age-dependent mechanisms that govern survival and control of virus infections at older age. url: https://doi.org/10.1101/2020.09.21.307017 doi: 10.1101/2020.09.21.307017 id: cord-103015-3dxwbmd2 author: Shengjuler, Djoshkun title: The RNA-binding site of poliovirus 3C protein doubles as a phosphoinositide-binding domain date: 2017-08-04 words: 7069.0 sentences: 411.0 pages: flesch: 63.0 cache: ./cache/cord-103015-3dxwbmd2.txt txt: ./txt/cord-103015-3dxwbmd2.txt summary: Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using NMR spectroscopy. 93 Validation of PIP-binding sites by NMR 94 In order to test the validity of our docking observations, we titrated 15 N-labeled 3C protein 95 with soluble dibutyl-PI4P to observe potential NMR chemical shift perturbations (CSPs), which 96 would indicate chemical environment changes in the presence of PI4P (Figure 2) . Out of the three 97 basic residues of the major cluster that were predicted to interact with the PI4P, R13 showed the 98 largest CSP (Figure 2A ). Titration of PI4P into a solution containing 3C caused CSPs that were consistent 249 with the major PI4P-binding site observed computationally (Figure 2A) . abstract: Some viruses use phosphatidylinositol phosphate (PIP) to mark membranes used for genome replication or virion assembly. PIP-binding motifs of cellular proteins do not exist in viral proteins. Molecular-docking simulations revealed a putative site of PIP binding to poliovirus (PV) 3C protein that was validated using NMR spectroscopy. The PIP-binding site was located on a highly dynamic α-helix that also functions in RNA binding. Broad PIP-binding activity was observed in solution using a fluorescence polarization assay or in the context of a lipid bilayer using an on-chip, fluorescence assay. All-atom molecular dynamics simulations of the 3C protein-membrane interface revealed PIP clustering and perhaps PIP-dependent conformations. PIP clustering was mediated by interaction with residues that interact with the RNA phosphodiester backbone. We conclude that 3C binding to membranes will be determined by PIP abundance. We suggest that the duality of function observed for 3C may extend to RNA-binding proteins of other viruses. Highlights A viral PIP-binding site identified, validated and characterized PIP-binding site overlaps the known RNA-binding site PIP-binding site clusters PIPs and perhaps regulates conformation and function Duality of PIP- and RNA-binding sites may extend to other viruses In Brief The absence of conventional PIP-binding domains in viral proteins suggests unique structural solutions to this problem. Shengjuler et al. show that a viral RNA-binding site can be repurposed for PIP binding. PIP clustering can be achieved. The nature of the PIP may regulate protein conformation. url: https://doi.org/10.1101/172742 doi: 10.1101/172742 id: cord-103940-a2cqw8kg author: Shi, Yuejun title: Insight into vaccine development for Alpha-coronaviruses based on structural and immunological analyses of spike proteins date: 2020-06-09 words: 3207.0 sentences: 216.0 pages: flesch: 63.0 cache: ./cache/cord-103940-a2cqw8kg.txt txt: ./txt/cord-103940-a2cqw8kg.txt summary: Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. In this study, 130 we selected SARS-CoV, SARS-CoV-2, and HCoV-229E as models, which adopt the 131 two RBD states, and evaluated and compared immune responses to the S trimers and 132 7 RBDs of these coronaviruses through immunological and bioinformatics approaches. 133 We also investigated the mechanism through which the HCoV-229E S trimer 134 produced effective nAbs. Finally, we provide possible vaccine strategies for alphaTo address this issue, we performed B-cell epitope predictions for the S trimers 152 and RBDs of alpha-CoV (HCoV-229E) and beta-CoVs (SARS-CoV and 153 SARS-CoV-2). Taken together, these results showed that the intact and stable S1 subunit of 240 HCoV-229E is a prerequisite for the production of effective nAbs. Furthermore, our experimental results show that RBD has a higher ability to bind 242 12 to the receptor hAPN (Fig. 4B) , which indicates that the characteristics of RBD itself 243 may lead to the generation of less neutralizing antibodies. abstract: Coronaviruses that infect humans belong to the Alpha-coronavirus (including HCoV-229E) and Beta-coronavirus (including SARS-CoV and SARS-CoV-2) genera. In particular, SARS-CoV-2 is currently a major threat to public health worldwide. However, no commercial vaccines against the coronaviruses that can infect humans are available. The spike (S) homotrimers bind to their receptors through the receptor-binding domain (RBD), which is believed to be a major target to block viral entry. In this study, we selected Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) as models. Their RBDs were observed to adopt two different conformational states (lying or standing). Then, structural and immunological analyses were used to explore differences in the immune response with RBDs among these coronaviruses. Our results showed that more RBD-specific antibodies were induced by the S trimer with the RBD in the “standing” state (SARS-CoV and SARS-CoV-2) than the S trimer with the RBD in the “lying” state (HCoV-229E), and the affinity between the RBD-specific antibodies and S trimer was also higher in the SARS-CoV and SARS-CoV-2. In addition, we found that the ability of the HCoV-229E RBD to induce neutralizing antibodies was much lower and the intact and stable S1 subunit was essential for producing efficient neutralizing antibodies against HCoV-229E. Importantly, our results reveal different vaccine strategies for coronaviruses, and S-trimer is better than RBD as a target for vaccine development in Alpha-coronavirus. Our findings will provide important implications for future development of coronavirus vaccines. Importance Outbreak of coronaviruses, especially SARS-CoV-2, poses a serious threat to global public health. Development of vaccines to prevent the coronaviruses that can infect humans has always been a top priority. Coronavirus spike (S) protein is considered as a major target for vaccine development. Currently, structural studies have shown that Alpha-coronavirus (HCoV-229E) and Beta-coronavirus (SARS-CoV and SARS-CoV-2) RBDs are in lying and standing state, respectively. Here, we tested the ability of S-trimer and RBD to induce neutralizing antibodies among these coronaviruses. Our results showed that Beta-CoVs RBDs are in a standing state, and their S proteins can induce more neutralizing antibodies targeting RBD. However, HCoV-229E RBD is in a lying state, and its S protein induces a low level of neutralizing antibody targeting RBD. Our results indicate that Alpha-coronavirus is more conducive to escape host immune recognition, and also provide novel ideas for the development of vaccines targeting S protein. url: https://doi.org/10.1101/2020.06.09.141580 doi: 10.1101/2020.06.09.141580 id: cord-103924-mhgnqi80 author: Shin, Donghyuk title: Novel class of OTU deubiquitinases regulate substrate ubiquitination upon Legionella infection date: 2020-04-28 words: 2096.0 sentences: 220.0 pages: flesch: 67.0 cache: ./cache/cord-103924-mhgnqi80.txt txt: ./txt/cord-103924-mhgnqi80.txt summary: MS analysis of catalytically inactive LotB and LotC identified different categories of host-substrates for these two related DUBs. Together, our results provide new structural insights of bacterial OTU deubiquitinases and indicate distinct roles of bacterial deubiquitinases in host-pathogen interactions. Whereas the overall fold of the 174 catalytic core of LotB and LotC resembles that of other OTU-deubiquitinases, both showed clear 175 differences in the helical arm region, which has been shown to interact with ubiquitin and it serves 176 as an S1 binding site (Mevissen et al., 2013) . To address this, we performed ubiquitin 192 docking into both LotB and LotC, followed by molecular dynamics (MD) simulations for 600 ns 193 ( Fig. 4aTo gain better insights into the physiological roles of LotB and LotC, we decided to identify their 216 interacting proteins or substrates. abstract: Legionella pneumophila is a gram-negative pathogenic bacterium that causes Legionaries’ disease. The Legionella genome codes more than 300 effector proteins able to modulate host-pathogen interactions during infection. Among them are also enzymes altering the host-ubiquitination system including bacterial ligases and deubiquitinases. In this study, based on homology-detection screening on 305 Legionella effector proteins, we identified two Legionella OTU-like deubiquitinases (LOT; LotB (Lpg1621/Ceg23) and LotC (Lpg2529), LotA (Lpg2248/Lem21) is already known). A crystal structure of LotC catalytic core (LotC14-310) was determined at 2.4 Å and compared with other OTU deubiquitinases, including LotB. Unlike the classical OTU-family, the structures of Legionella OTU-family (LotB and LotC) shows an extended helical lobe between the Cys-loop and the variable loop, which define a novel class of OTU-deubiquitinase. Despite structural differences in their helical lobes, both LotB and LotC interact with ubiquitin. LotB has an additional ubiquitin binding site (S1’) enabling specific cleavage of Lys63-linked poly-ubiquitin chains. By contrast, LotC only contains the S1 site and cleaves different species of ubiquitin chains. MS analysis of catalytically inactive LotB and LotC identified different categories of host-substrates for these two related DUBs. Together, our results provide new structural insights of bacterial OTU deubiquitinases and indicate distinct roles of bacterial deubiquitinases in host-pathogen interactions. url: https://doi.org/10.1101/2020.04.25.060954 doi: 10.1101/2020.04.25.060954 id: cord-254636-3lr008th author: Shishir, Tushar Ahmed title: In silico comparative genomics of SARS-CoV-2 to determine the source and diversity of the pathogen in Bangladesh date: 2020-08-16 words: 2974.0 sentences: 171.0 pages: flesch: 54.0 cache: ./cache/cord-254636-3lr008th.txt txt: ./txt/cord-254636-3lr008th.txt summary: We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. We conducted comparative analysis of publicly available genome sequences of SARS-CoV-2 from 27 countries to predict the origin of viruses in Bangladesh by studying a time-4 resolved phylogenetic relationship. Later, we analyzed the variants present in different isolates of Bangladesh to understand the pattern of mutations in relation to the ancestral Wuhan strain, find unique mutations, and possible effect of these mutations on the stability of encoded proteins, and selection pressure on genes. abstract: The COVID19 pandemic caused by SARS-CoV-2 virus has severely affected most countries of the world including Bangladesh. We conducted comparative analysis of publicly available whole-genome sequences of 64 SARS-CoV-2 isolates in Bangladesh and 371 isolates from another 27 countries to predict possible transmission routes of COVID19 to Bangladesh and genomic variations among the viruses. Phylogenetic analysis indicated that the pathogen was imported in Bangladesh from multiple countries. The viruses found in the southern district of Chattogram were closely related to strains from Saudi Arabia whereas those in Dhaka were similar to that of United Kingdom and France. The 64 SARS-CoV-2 sequences from Bangladesh belonged to three clusters. Compared to the ancestral SARS-CoV-2 sequence reported from China, the isolates in Bangladesh had a total of 180 mutations in the coding region of the genome, and 110 of these were missense. Among these, 99 missense mutations (90%) were predicted to destabilize protein structures. Remarkably, a mutation that leads to an I300F change in the nsp2 protein and a mutation leading to D614G change in the spike protein were prevalent in SARS-CoV-2 genomic sequences, and might have influenced the epidemiological properties of the virus in Bangladesh. url: https://doi.org/10.1101/2020.07.20.212563 doi: 10.1101/2020.07.20.212563 id: cord-331611-pwj226j0 author: Shrimp, Jonathan H. title: An Enzymatic TMPRSS2 Assay for Assessment of Clinical Candidates and Discovery of Inhibitors as Potential Treatment of COVID-19 date: 2020-06-23 words: 3894.0 sentences: 216.0 pages: flesch: 45.0 cache: ./cache/cord-331611-pwj226j0.txt txt: ./txt/cord-331611-pwj226j0.txt summary: We demonstrate effectiveness to quantify inhibition down to subnanomolar concentrations by assessing the inhibition of camostat, nafamostat and gabexate, clinically approved agents in Japan for pancreatitis due to their inhibition of trypsin-like proteases. The structurally related trypsin-like serine protease inhibitor nafamostat was shown to similarly inhibit spike protein-mediated cell fusion of MERS-CoV 7 . Herein we report the development of a TMPRSS2 fluorogenic biochemical assay and testing of clinical repurposing candidates for COVID19. To identify inhibitors of TMPRSS2 that may be used to validate its role in SARS-CoV-2 entry and potentially expedite to clinical trials, we developed a biochemical assay using active TMPRSS2 protease and a fluorogenic peptide substrate ( Figure 1B) . We developed a fluorogenic biochemical assay for measuring recombinant human TMPRSS2 activity for high-throughput screening that can be readily replicated and used to demonstrate that nafamostat is a more potent inhibitor than camostat and gabexate. abstract: SARS-CoV-2 is the viral pathogen causing the COVID19 global pandemic. Consequently, much research has gone into the development of pre-clinical assays for the discovery of new or repurposing of FDA-approved therapies. Preventing viral entry into a host cell would be an effective antiviral strategy. One mechanism for SARS-CoV-2 entry occurs when the spike protein on the surface of SARS-CoV-2 binds to an ACE2 receptor followed by cleavage at two cut sites (“priming”) that causes a conformational change allowing for viral and host membrane fusion. This fusion event is proceeded by release of viral RNA within the host cell. TMPRSS2 has an extracellular protease domain capable of cleaving the spike protein to initiate membrane fusion. Additionally, knock-out studies in mice have demonstrated reduced infection in the absence of TMPRSS2 with no detectable physiological impact; thus, TMPRSS2 is an attractive target for therapeutic development. A validated inhibitor of TMPRSS2 protease activity would be a valuable tool for studying the impact TMPRSS2 has in viral entry and potentially be an effective antiviral therapeutic. To enable inhibitor discovery and profiling of FDA-approved therapeutics, we describe an assay for the biochemical screening of recombinant TMPRSS2 suitable for high throughput application. We demonstrate effectiveness to quantify inhibition down to subnanomolar concentrations by assessing the inhibition of camostat, nafamostat and gabexate, clinically approved agents in Japan for pancreatitis due to their inhibition of trypsin-like proteases. Nafamostat and camostat are currently in clinical trials against COVID19. The rank order potency for the three inhibitors is: nafamostat (IC(50) = 0.27 nM), camostat (IC(50) = 6.2 nM) and gabexate (IC(50) = 130 nM). Further profiling of these three inhibitors against a panel of proteases provides insight into selectivity and potency. url: https://www.ncbi.nlm.nih.gov/pubmed/32596694/ doi: 10.1101/2020.06.23.167544 id: cord-102809-06izdji8 author: Siddiqui, Nabil A. title: Radiolabelled Bacterial Metallophores as Targeted PET Imaging Contrast Agents for Accurate Identification of Bacteria and Outer Membrane Vesicles in vivo date: 2020-08-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Modern technologies such as 16s DNA sequencing capable of identifying microbes and provide taxonomic resolution at species and strain-specific levels is destined to be transformative1. Likewise, there is an emerging need to accurately identify both infectious and non-infectious microbes non-invasively in the body at the genus and species level to guide diagnosis and treatment strategies. Here, we report development of radiometal-labelled bacterial chelators, knowns as metallophores that allow non-invasive and selective imaging of bacteria and bacterial products in vivo. We show that these novel contrast agents are able to identify E. coli with strain level specificity and other bacteria, such as K. pneumoniae, based on expression of distinct cognate transporters on the bacterial surface. The probe is also capable of tracking probiotic, engineered bacteria and bacterial products, outer membrane vesicles (OMVs), in unique niches such as tumours. Moreover, we report that this novel targeted imaging approach has impactful applicability in monitoring antibiotic treatment outcomes in patients with pulmonary infections, thereby providing the ability to optimize individualized therapeutic approaches. Compared to traditional techniques used to manufacture probes, this strategy simplifies the process considerably by combining the function of metal attachment and cell recognition into a single molecule. Thus, we anticipate that these probes will be widely used in both clinical and investigative settings in living systems for non-invasive imaging of infectious and non-infectious organisms. url: https://doi.org/10.1101/2020.08.06.240119 doi: 10.1101/2020.08.06.240119 id: cord-102668-1yc38ok1 author: Siddiqui, Shoib S. title: Acidosis, Zinc and HMGB1 in Sepsis: A Common Connection Involving Sialoglycan Recognition date: 2020-07-15 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Blood pH is tightly regulated between 7.35-7.45, with values below 7.3 during sepsis being associated with lactic acidosis, low serum zinc, and release of proinflammatory HMGB1 from activated and/or necrotic cells. Using an ex vivo whole blood system to model lactic acidosis, we show that while HMGB1 does not engage leukocyte receptors at physiological pH, lowering pH with lactic acid facilitates binding. At normal pH, micromolar zinc supports plasma sialoglycoprotein binding by HMGB1, which is markedly reduced when pH is adjusted with lactic acid to sepsis levels. Glycan array studies confirmed zinc and pH-dependent HMGB1 binding to sialoglycans typical of plasma glycoproteins. Thus, proinflammatory effects of HMGB1 are suppressed via plasma sialoglycoproteins until drops in pH and zinc release HMGB1 to trigger downstream immune activation. Significance Statement HMGB1 sequestered by plasma sialoglycoproteins at physiological pH is released when pH and zinc concentrations fall in sepsis. url: https://doi.org/10.1101/2020.07.15.198010 doi: 10.1101/2020.07.15.198010 id: cord-312473-7i7efdp2 author: Sidhom, John-William title: Analysis of SARS-CoV-2 specific T-cell receptors in ImmuneCode reveals cross-reactivity to immunodominant Influenza M1 epitope date: 2020-06-20 words: 1181.0 sentences: 62.0 pages: flesch: 46.0 cache: ./cache/cord-312473-7i7efdp2.txt txt: ./txt/cord-312473-7i7efdp2.txt summary: We first examined the distribution of TCRs within the McPas database over the types of pathogens present in the database and cross-referenced the SARS-CoV-2 specific TCRs into the McPas database ( Figure 1A) , and we noted that there was a statistically significant enrichment (from 17.3% to 32.9%) of SARS-CoV-2 specific TCRs that had known specificity to the immunodominant M1 GILGFVFTL epitope We then examined the distribution of TCRs within the ImmuneCode database across the various open readings frames (orfs) and mapped the M1 specific TCRs within this database ( Figure 1B) . In conclusion, while these results are preliminary in a small cohort of individuals, we have identified a set of TCRs that is known to both recognize an immunodominant epitope derived from Influenza and SARS-CoV-2, suggesting that immune control of one infection may play a role in the control of the other. abstract: Adaptive Biotechnologies and Microsoft have recently partnered to release ImmuneCode, a database containing SARS-CoV-2 specific T-cell receptors derived through MIRA, a T-cell receptor (TCR) sequencing based sequencing approach to identify antigen-specific TCRs. Herein, we query the extent of cross reactivity between these derived SARS-CoV-2 specific TCRs and other known antigens present in McPas-TCR, a manually curated catalogue of pathology-associated TCRs. We reveal cross reactivity between SARS-CoV-2 specific TCRs and the immunodominant Influenza GILGFVFTL M1 epitope, suggesting the importance of further work in characterizing the implications of prior Influenza exposure or co-exposure to the pathology of SARS-CoV-2 illness. url: https://doi.org/10.1101/2020.06.20.160499 doi: 10.1101/2020.06.20.160499 id: cord-296997-ba7f2mf3 author: Sikora, Mateusz title: Map of SARS-CoV-2 spike epitopes not shielded by glycans date: 2020-07-03 words: 5818.0 sentences: 371.0 pages: flesch: 55.0 cache: ./cache/cord-296997-ba7f2mf3.txt txt: ./txt/cord-296997-ba7f2mf3.txt summary: To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. Our simulation system contained four membrane-embedded SARS-CoV-2 S proteins assembled from resolved structures where available and models for the missing parts (SI Appendix, Fig. S5 ). In the ray analysis, we illuminated the protein model by diffuse light; in the Fab docking analysis, we performed rigid body Monte Carlo simulations of S and the SARS-CoV-2 antibody CR3022 Fab to determine the steric accessibility to an antibody Fab. To account for protein and glycan mobility, we performed both analyses individually for 4 × 193 snapshots taken at 10 ns time intervals from the 1.93 µs MD simulation with four glycosylated S proteins. abstract: The severity of the COVID-19 pandemic, caused by the SARS-CoV-2 coronavirus, calls for the urgent development of a vaccine. The primary immunological target is the SARS-CoV-2 spike (S) protein. S is exposed on the viral surface to mediate viral entry into the host cell. To identify possible antibody binding sites not shielded by glycans, we performed multi-microsecond molecular dynamics simulations of a 4.1 million atom system containing a patch of viral membrane with four full-length, fully glycosylated and palmitoylated S proteins. By mapping steric accessibility, structural rigidity, sequence conservation and generic antibody binding signatures, we recover known epitopes on S and reveal promising epitope candidates for vaccine development. We find that the extensive and inherently flexible glycan coat shields a surface area larger than expected from static structures, highlighting the importance of structural dynamics in epitope mapping. url: https://doi.org/10.1101/2020.07.03.186825 doi: 10.1101/2020.07.03.186825 id: cord-295765-c7o2ukm6 author: Silvas, Jesus A. title: Inhibitors of VPS34 and lipid metabolism suppress SARS-CoV-2 replication date: 2020-07-20 words: 2234.0 sentences: 145.0 pages: flesch: 53.0 cache: ./cache/cord-295765-c7o2ukm6.txt txt: ./txt/cord-295765-c7o2ukm6.txt summary: VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. As SARS-CoV-2 replication 174 damages the cell monolayer, impedance measurements decrease over time, providing a detailed 175 assessment of infection kinetics. Based on the toxicity window of 1-20 221 h.p.t. determined with the VPS34 inhibitors, neither Triacsin C nor Orlistat induced early 222 cytotoxic effects, even at the highest concentrations of 50uM and 500uM, respectively ( Figure 223 3A and 3C). Here, we demonstrate that two VPS34 inhibitors, Orlistat, and Triacsin C each have clear effects 308 on SARS-CoV-2 replication and the morphology of viral replication centers. In contrast, the compounds did not exhibit any activity against 384 SARS-CoV-2 in Vero E6 cells whereas Triacsin C did. abstract: Therapeutics targeting replication of SARS coronavirus 2 (SARS-CoV-2) are urgently needed. Coronaviruses rely on host membranes for entry, establishment of replication centers and egress. Compounds targeting cellular membrane biology and lipid biosynthetic pathways have previously shown promise as antivirals and are actively being pursued as treatments for other conditions. Here, we tested small molecule inhibitors that target membrane dynamics or lipid metabolism. Included were inhibitors of the PI3 kinase VPS34, which functions in autophagy, endocytosis and other processes; Orlistat, an inhibitor of lipases and fatty acid synthetase, is approved by the FDA as a treatment for obesity; and Triacsin C which inhibits long chain fatty acyl-CoA synthetases. VPS34 inhibitors, Orlistat and Triacsin C inhibited virus growth in Vero E6 cells and in the human airway epithelial cell line Calu-3, acting at a post-entry step in the virus replication cycle. Of these the VPS34 inhibitors exhibit the most potent activity. url: https://doi.org/10.1101/2020.07.18.210211 doi: 10.1101/2020.07.18.210211 id: cord-326257-rcv8sh22 author: Simmonds, P. title: Rampant C->U hypermutation in the genomes of SARS-CoV-2 and other coronaviruses – causes and consequences for their short and long evolutionary trajectories date: 2020-05-01 words: 3499.0 sentences: 172.0 pages: flesch: 47.0 cache: ./cache/cord-326257-rcv8sh22.txt txt: ./txt/cord-326257-rcv8sh22.txt summary: C->U transitions underpinned almost half of the amino acid differences between SARS-CoV-2 variants, and occurred preferentially in both 5''U/A and 3''U/A flanking sequence contexts comparable to favoured motifs of human APOBEC3 proteins. Importance The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short and long term evolution. The possibility that the initial diversity within a viral population was largely host-induced would have major implications for 70 evolutionary reconstruction of SARS-CoV-2 variants in the current pandemic, as well as in our understanding both of host antiviral pathways against coronaviruses and the longer term shaping effects on their genome composition. To formally analyse 105 the excess of C->U transitions we calculated an index of asymmetry (frequency[C->U] / f[U->C]) x (fU/fC) and compared this with degrees of sequence divergence and dN/dS ratio in SARS-CoV-2 and other coronavirus datasets (Fig. 2B, 2C ). abstract: The pandemic of SARS coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a dataset of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean 5.5-9.5 nucleotide differences from each other, commensurate with a mid-range coronavirus substitution rate of 3×10−4 substitutions/site/year. Almost half of sequence changes were C->U transitions with an 8-fold base frequency normalised directional asymmetry between C->U and U->C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV and MERS-CoV) and to a decreasing degree in other human coronaviruses (HCoV-NL63, -OC43, -229E and -HKU1) proportionate to their increasing divergence. C->U transitions underpinned almost half of the amino acid differences between SARS-CoV-2 variants, and occurred preferentially in both 5’U/A and 3’U/A flanking sequence contexts comparable to favoured motifs of human APOBEC3 proteins. Marked base asymmetries observed in non-pandemic human coronaviruses (U>>A>G>>C) and low G+C contents may represent long term effects of prolonged C->U hypermutation in their hosts. Importance The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short and long term evolution. Repeated cycles of mutation and reversion in favoured mutational hotspots and the widespread occurrence of amino acid changes with no adaptive value for the virus represents a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks that are typically used in molecular epidemiology investigations. url: https://doi.org/10.1101/2020.05.01.072330 doi: 10.1101/2020.05.01.072330 id: cord-290290-wyx9ib7s author: Sinegubova, Maria V. title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector date: 2020-11-05 words: 5978.0 sentences: 304.0 pages: flesch: 49.0 cache: ./cache/cord-290290-wyx9ib7s.txt txt: ./txt/cord-290290-wyx9ib7s.txt summary: title: High-level expression of the monomeric SARS-CoV-2 S protein RBD 320-537 in stably transfected CHO cells by the EEF1A1-based plasmid vector Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. Previously we have developed the plasmid vector p1.1, containing large fragments of non-coding DNA from the EEF1A1 gene of the Chinese hamster and fragment of the Epstein-Barr virus long terminal repeat concatemer [21] and employed it for unusually high-level expression of various proteins in CHO cells, including blood clotting factors VIII [22] , IX [23] , and heterodimeric follicle-stimulating hormone [24] . We have proposed that SARS-CoV-2 RBD, suitable for in vitro diagnostics use, may be expressed in large quantities by stably transfected CHO cells, bearing the EEF1A1-based plasmid. abstract: The spike (S) protein is one of the three proteins forming the coronaviruses’ viral envelope. The S protein of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has a spatial structure similar to the S proteins of other mammalian coronaviruses, except for a unique receptor-binding domain (RBD), which is a significant inducer of host immune response. Recombinant SARS-CoV-2 RBD is widely used as a highly specific minimal antigen for serological tests. Correct exposure of antigenic determinants has a significant impact on the accuracy of such tests – the antigen has to be correctly folded, contain no potentially antigenic non-vertebrate glycans, and, preferably, should have a glycosylation pattern similar to the native S protein. Based on the previously developed p1.1 vector, containing the regulatory sequences of the Eukaryotic translation elongation factor 1 alpha gene (EEF1A1) from Chinese hamster, we created two expression constructs encoding SARS-CoV-2 RBD with C-terminal c-myc and polyhistidine tags. RBDv1 contained a native viral signal peptide, RBDv2 – human tPA signal peptide. We transfected a CHO DG44 cell line, selected stably transfected cells, and performed a few rounds of methotrexate-driven amplification of the genetic cassette in the genome. For the RBDv2 variant, a high-yield clonal producer cell line was obtained. We developed a simple purification scheme that consistently yielded up to 30 mg of RBD protein per liter of the simple shake flask cell culture. Purified proteins were analyzed by polyacrylamide gel electrophoresis in reducing and non-reducing conditions and gel filtration; for RBDv2 protein, the monomeric form content exceeded 90% for several series. Deglycosylation with PNGase F and mass spectrometry confirmed the presence of N-glycosylation. The antigen produced by the described technique is suitable for serological tests and similar applications. url: https://doi.org/10.1101/2020.11.04.368092 doi: 10.1101/2020.11.04.368092 id: cord-288705-f3zqhpx1 author: Slaine, Patrick title: Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model date: 2020-10-01 words: 5892.0 sentences: 325.0 pages: flesch: 45.0 cache: ./cache/cord-288705-f3zqhpx1.txt txt: ./txt/cord-288705-f3zqhpx1.txt summary: title: Thiopurines activate an antiviral unfolded protein response that blocks viral glycoprotein accumulation in cell culture infection model Selective disruption of IAV glycoprotein processing and accumulation by 6-TG and 6-TGo correlated with unfolded protein response (UPR) activation and HA accumulation could be partially restored by the chemical chaperone 4-phenylbutyrate (4PBA). Thiopurines inhibited replication of the human coronavirus OC43 (HCoV-OC43), which also correlated with UPR/ISR activation and diminished accumulation of ORF1ab and nucleocapsid (N) mRNAs and N protein, which suggests broader disruption of coronavirus gene expression in ER-derived cytoplasmic compartments. Our results suggest that 406 the effects are unlikely to be mediated through DNA or RNA incorporation of 6-TG because 1) 407 replicative stress does not specifically induce UPR; 2) among viral proteins, glycoprotein 408 accumulation and processing was preferentially disrupted; 3) messenger RNA levels of HA and 409 NA were not affected. abstract: Enveloped viruses, including influenza A viruses (IAVs) and coronaviruses (CoVs), utilize the host cell secretory pathway to synthesize viral glycoproteins and direct them to sites of assembly. Using an image-based high-content screen, we identified two thiopurines, 6-thioguanine (6-TG) and 6-thioguanosine (6-TGo), that selectively disrupted the processing and accumulation of IAV glycoproteins hemagglutinin (HA) and neuraminidase (NA). Selective disruption of IAV glycoprotein processing and accumulation by 6-TG and 6-TGo correlated with unfolded protein response (UPR) activation and HA accumulation could be partially restored by the chemical chaperone 4-phenylbutyrate (4PBA). Chemical inhibition of the integrated stress response (ISR) restored accumulation of NA monomers in the presence of 6-TG or 6-TGo, but did not restore NA glycosylation or oligomerization. Thiopurines inhibited replication of the human coronavirus OC43 (HCoV-OC43), which also correlated with UPR/ISR activation and diminished accumulation of ORF1ab and nucleocapsid (N) mRNAs and N protein, which suggests broader disruption of coronavirus gene expression in ER-derived cytoplasmic compartments. The chemically similar thiopurine 6-mercaptopurine (6-MP) had little effect on the UPR and did not affect IAV or HCoV-OC43 replication. Consistent with reports on other CoV Spike (S) proteins, ectopic expression of SARS-CoV-2 S protein caused UPR activation. 6-TG treatment inhibited accumulation of full length S0 or furin-cleaved S2 fusion proteins, but spared the S1 ectodomain. DBeQ, which inhibits the p97 AAA-ATPase required for retrotranslocation of ubiquitinated misfolded proteins during ER-associated degradation (ERAD) restored accumulation of S0 and S2 proteins in the presence of 6-TG, suggesting that 6-TG induced UPR accelerates ERAD-mediated turnover of membrane-anchored S0 and S2 glycoproteins. Taken together, these data indicate that 6-TG and 6-TGo are effective host-targeted antivirals that trigger the UPR and disrupt accumulation of viral glycoproteins. Importantly, our data demonstrate for the first time the efficacy of these thiopurines in limiting IAV and HCoV-OC43 replication in cell culture models. IMPORTANCE Secreted and transmembrane proteins are synthesized in the endoplasmic reticulum (ER), where they are folded and modified prior to transport. During infection, many viruses burden the ER with the task of creating and processing viral glycoproteins that will ultimately be incorporated into viral envelopes. Some viruses refashion the ER into replication compartments where viral gene expression and genome replication take place. This viral burden on the ER can trigger the cellular unfolded protein response (UPR), which attempts to increase the protein folding and processing capacity of the ER to match the protein load. Much remains to be learned about how viruses co-opt the UPR to ensure efficient synthesis of viral glycoproteins. Here, we show that two FDA-approved thiopurine drugs, 6-TG and 6-TGo, induce the UPR in a manner that impedes viral glycoprotein accumulation for enveloped influenza viruses and coronaviruses. These drugs may impede the replication of viruses that require precise tuning of the UPR to support viral glycoprotein synthesis for the successful completion of a replication cycle. url: https://doi.org/10.1101/2020.09.30.319863 doi: 10.1101/2020.09.30.319863 id: cord-103538-vh6ma7k7 author: Smaldino, Paul E. title: Coupled Dynamics of Behavior and Disease Contagion Among Antagonistic Groups date: 2020-10-05 words: 4978.0 sentences: 257.0 pages: flesch: 49.0 cache: ./cache/cord-103538-vh6ma7k7.txt txt: ./txt/cord-103538-vh6ma7k7.txt summary: We analyze a simple model of coupled behavior-change and infection in a structured population characterized by homophily and outgroup aversion. While we might expect strong selection-both biological and cultural-for adaptive responses to epidemics, complications such as the potentially differing time 33 scales of culture and disease transmission and the existence of social structures that shape adoption may complicate convergence to adaptive behavioral solutions. Unlike a disease, which is reasonably modeled as equally transmissible between any susceptible-infected pairing, where behavior is concerned, susceptible individuals are more likely to adopt when interacting with in-126 group adopters, but less likely to adopt when interacting with outgroup adopters. Not so with outgroup aversion, in which the peak infection rates increase relative to the low homophily case ( Figure 3E , F). However, when R 0 is high enough and outgroup aversion induces 258 group differences in behavior adoption, strong homophily among group 2 can lead to larger, albeit delayed, epidemics in the initially-uninfected segment of the population. abstract: Disease transmission and behavior change are both fundamentally social phenomena. Behavior change can have profound consequences for disease transmission, and epidemic conditions can favor the more rapid adoption of behavioral innovations. We analyze a simple model of coupled behavior-change and infection in a structured population characterized by homophily and outgroup aversion. Outgroup aversion slows the rate of adoption and can lead to lower rates of adoption in the later-adopting group or even behavioral divergence between groups when outgroup aversion exceeds positive ingroup influence. When disease dynamics are coupled to the behavior-adoption model, a wide variety of outcomes are possible. Homophily can either increase or decrease the final size of the epidemic depending on its relative strength in the two groups and on R0 for the infection. For example, if the first group is homophilous and the second is not, the second group will have a larger epidemic. Homophily and outgroup aversion can also produce dynamics suggestive of a “second wave” in the first group that follows the peak of the epidemic in the second group. Our simple model reveals complex dynamics that are suggestive of the processes currently observed under pandemic conditions in culturally and/or politically polarized populations such as the United States. url: https://doi.org/10.1101/2020.06.17.157511 doi: 10.1101/2020.06.17.157511 id: cord-103163-0rreoh4o author: Smith, Sydni Caet title: Reovirus RNA recombination is sequence directed and generates internally deleted defective genome segments during passage date: 2020-10-22 words: 8965.0 sentences: 456.0 pages: flesch: 46.0 cache: ./cache/cord-103163-0rreoh4o.txt txt: ./txt/cord-103163-0rreoh4o.txt summary: We determined the titers and RNA segment profiles of reovirus (rsT1L and rsT3D I ) and rotavirus (rsSA11) laboratory strains that had been rescued by reverse genetics then serially passaged ten times, each in triplicate lineages, in cultured cells. The two reoviruses accumulated non-canonical RNAs that retain 5′ and 3′ termini and feature one or more large internal deletions, while the rotavirus rarely accumulated such DVGs. Analyses of next-generation RNA-sequencing data sets from purified rsT1L reovirus RNA revealed many junctions, with hot spots for recombination in specific viral gene segments. Taken together, lin1 RNA profiles suggest non-canonical RNA species that differ in length but have identical termini to the parental segments accumulate variably during reovirus and rotavirus serial passage in cultured cells. abstract: For viruses with segmented genomes, genetic diversity is generated by genetic drift, reassortment, and recombination. Recombination produces RNA populations distinct from full-length gene segments and can influence viral population dynamics, persistence, and host immune responses. Viruses in the Reoviridae family, including rotavirus and mammalian orthoreovirus (reovirus), have been reported to package segments containing rearrangements or internal deletions. Rotaviruses with RNA segments containing rearrangements have been isolated from immunocompromised and immunocompetent children and in vitro following serial passage at high multiplicity. Reoviruses that package small, defective RNA segments have established chronic infections in cells and in mice. However, the mechanism and extent of Reoviridae RNA recombination are undefined. Towards filling this gap in knowledge, we determined the titers and RNA segment profiles for reovirus and rotavirus following serial passage in cultured cells. The viruses exhibited occasional titer reductions characteristic of interference. Reovirus strains frequently accumulated segments that retained 5′ and 3′ terminal sequences and featured large internal deletions, while similar segments were rarely detected in rotavirus populations. Using next-generation RNA-sequencing to analyze RNA molecules packaged in purified reovirus particles, we identified distinct recombination sites within individual viral gene segments. Recombination junction sites were frequently associated with short regions of identical sequence. Taken together, these findings suggest that reovirus accumulates defective gene segments featuring internal deletions during passage and undergoes sequence-directed recombination at distinct sites. IMPORTANCE Viruses in the Reoviridae family include important pathogens of humans and other animals and have segmented RNA genomes. Recombination in RNA virus populations can facilitate novel host exploration and increased disease severity. The extent, patterns, and mechanisms of Reoviridae recombination and the functions and effects of recombined RNA products are poorly understood. Here, we provide evidence that mammalian orthoreovirus regularly synthesizes RNA recombination products that retain terminal sequences but contain internal deletions, while rotavirus rarely synthesizes such products. Recombination occurs more frequently at specific sites in the mammalian orthoreovirus genome, and short regions of identical sequence are often detected at junction sites. These findings suggest that mammalian orthoreovirus recombination events are directed in part by RNA sequences. An improved understanding of recombined viral RNA synthesis may enhance our capacity to engineer improved vaccines and virotherapies in the future. url: https://doi.org/10.1101/2020.10.19.346031 doi: 10.1101/2020.10.19.346031 id: cord-103739-mmkrwj8t author: Snijder, Eric J. title: A unifying structural and functional model of the coronavirus replication organelle: tracking down RNA synthesis date: 2020-03-24 words: 3808.0 sentences: 223.0 pages: flesch: 48.0 cache: ./cache/cord-103739-mmkrwj8t.txt txt: ./txt/cord-103739-mmkrwj8t.txt summary: Metabolic labelling of newly-synthesized viral RNA followed by quantitative EM autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs MERS-CoV and SARS-CoV, and the gamma-CoV infectious bronchitis virus. In infected cells, the CoV RNA-23 synthesizing machinery associates with modified endoplasmic reticulum membranes that are 24 transformed into the viral replication organelle (RO). In infected cells, the CoV RNA-23 synthesizing machinery associates with modified endoplasmic reticulum membranes that are 24 transformed into the viral replication organelle (RO). 106 double-membrane spherules (DMSs) 107 We first set out to analyse the ultrastructure of MERS-CoV-infected Huh7 cells under sample 108 preparation conditions favourable for autoradiography (see Materials and Methods) (Fig 1, S1 109 Video). Association of polioviral proteins of the P2 89 genomic region with the viral replication complex and virus-induced membrane synthesis as 90 visualized by electron microscopic immunocytochemistry and autoradiography abstract: Zoonotic coronavirus (CoV) infections, like those responsible for the current SARS-CoV-2 epidemic, cause grave international public health concern. In infected cells, the CoV RNA-synthesizing machinery associates with modified endoplasmic reticulum membranes that are transformed into the viral replication organelle (RO). While double-membrane vesicles (DMVs) appear to be a pan-coronavirus RO element, studies to date describe an assortment of additional coronavirus-induced membrane structures. Despite much speculation, it remains unclear which RO element(s) accommodate viral RNA synthesis. Here we provide detailed 2D and 3D analyses of CoV ROs and show that diverse CoVs essentially induce the same membrane modifications, including the small open double-membrane spherules (DMSs) previously thought to be restricted to gamma- and delta-CoV infections and proposed as sites of replication. Metabolic labelling of newly-synthesized viral RNA followed by quantitative EM autoradiography revealed abundant viral RNA synthesis associated with DMVs in cells infected with the beta-CoVs MERS-CoV and SARS-CoV, and the gamma-CoV infectious bronchitis virus. RNA synthesis could not be linked to DMSs or any other cellular or virus-induced structure. Our results provide a unifying model of the CoV RO and clearly establish DMVs as the central hub for viral RNA synthesis and a potential drug target in coronavirus infection. url: https://doi.org/10.1101/2020.03.24.005298 doi: 10.1101/2020.03.24.005298 id: cord-305858-gp1u4kh7 author: Song, Xiang title: High expression of angiotensin-converting enzyme-2 (ACE2) on tissue macrophages that may be targeted by virus SARS-CoV-2 in COVID-19 patients date: 2020-07-19 words: 4896.0 sentences: 268.0 pages: flesch: 49.0 cache: ./cache/cord-305858-gp1u4kh7.txt txt: ./txt/cord-305858-gp1u4kh7.txt summary: To better understand the pathogenesis of COVID-19 and build up the host anti-viral immunity, we examined the levels of ACE2 expression on different types of immune cells including tissue macrophages. To determine whether platelets were directly targeted by SARS-CoV-2 or trigged by viral inflammatory reactions, we examined the ACE2 expression on the highly-purified CD41b + CD42a + platelets from human peripheral blood ( Figure 3A Our previous work established that platelets could release mitochondria contributing to the immune modulation and islet b-cell regeneration [13] . Thus, the virus-infected alveolar macrophages play a critical role in the pathogenesis of COVID-19 and SARS [28] [29] [30] and may recruit the lung infiltration of additional immune cells through predominantly releasing cytokines and chemokines [31, 32] , resulting in pulmonary edema and hypoxemia: the hallmark of acute respiratory distress syndrome (ARDS) ( Figure 6 ). abstract: Angiotensin-converting enzyme-2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that infects host cells, causing the development of the new coronavirus infectious disease (COVID-19). To better understand the pathogenesis of COVID-19 and build up the host anti-viral immunity, we examined the levels of ACE2 expression on different types of immune cells including tissue macrophages. Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood-derived immune cells including CD4+ T, CD8+ T, activated CD4+ T, activated CD8+ T, CD4+CD25+CD127low/− regulatory T cells (Tregs), Th17 cells, NKT cells, B cells, NK cells, monocytes, dendritic cells (DCs), and granulocytes. Additionally, there was no ACE2 expression (< 1%) found on platelets. Compared with interleukin-4-treated type 2 macrophages (M2), the ACE2 expression was markedly increased on the activated type 1 macrophages (M1) after the stimulation with lipopolysaccharide (LPS). Immunohistochemistry demonstrated that high expressions of ACE2 were colocalized with tissue macrophages, such as alveolar macrophages found within the lungs and Kupffer cells within livers of mice. Flow cytometry confirmed the very low level of ACE2 expression on human primary pulmonary alveolar epithelial cells. These data indicate that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS-CoV-2 infection and therefore need to be considered for the prevention and treatment of COVID-19. url: https://doi.org/10.1101/2020.07.18.210120 doi: 10.1101/2020.07.18.210120 id: cord-102486-llmfgavd author: Sprenger, Kayla G. title: Optimizing immunization protocols to elicit broadly neutralizing antibodies date: 2020-01-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Natural infections and vaccination with a pathogen typically stimulates the production of potent antibodies specific for the pathogen through a Darwinian evolutionary process known as affinity maturation. Such antibodies provide protection against reinfection by the same strain of a pathogen. A highly mutable virus, like HIV or influenza, evades recognition by these strain-specific antibodies via the emergence of new mutant strains. A vaccine that elicits antibodies that can bind to many diverse strains of the virus – known as broadly neutralizing antibodies (bnAbs) – could protect against highly mutable pathogens. Despite much work, the mechanisms by which bnAbs emerge remain uncertain. Using a computational model of affinity maturation, we studied a wide variety of vaccination strategies. Our results suggest that an effective strategy to maximize bnAb evolution is through a sequential immunization protocol, wherein each new immunization optimally increases the pressure on the immune system to target conserved antigenic sites, thus conferring breadth. We describe the mechanisms underlying why sequentially driving the immune system increasingly further from equilibrium, in an optimal fashion, is effective. The optimal protocol allows many evolving B cells to become bnAbs via diverse evolutionary paths. Significance Statement The global health burden could be substantially alleviated by the creation of universal vaccines against highly mutable pathogens like HIV and influenza. Broadly-neutralizing antibodies (bnAbs) are encouraging targets for such vaccines, because they can bind to diverse strains of highly mutable pathogens. BnAbs typically develop only rarely upon natural infection, after the immune system has been exposed to many mutated versions of a pathogen. Thus, sequentially administering multiple different pathogen-like proteins (antigens) is a promising strategy to elicit bnAbs through vaccination. However, it remains unclear how best to design and administer these antigens. We explore this matter using physics-based simulations, and provide new mechanistic insights into antibody evolution that could guide the creation of universal vaccines against highly mutable pathogens. url: https://doi.org/10.1101/2020.01.04.894857 doi: 10.1101/2020.01.04.894857 id: cord-340432-vm6m0kb4 author: Srivastava, Sukrit title: Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide date: 2020-09-06 words: 2661.0 sentences: 199.0 pages: flesch: 54.0 cache: ./cache/cord-340432-vm6m0kb4.txt txt: ./txt/cord-340432-vm6m0kb4.txt summary: title: Computationally validated SARS-CoV-2 CTL and HTL Multi-Patch Vaccines designed by reverse epitomics approach, shows potential to cover large ethnically distributed human population worldwide Methodology A novel reverse epitomics approach, "overlapping-epitope-clusters-to-patches" method is utilized to identify multiple antigenic regions from the SARS-CoV-2 proteome. Multi-Patch Vaccine designing to combat SARS-CoV-2 infection by reverse epitomics approach, "Overlapping-epitope-clusters-to-patches" method. In the present study, we have reported a novel method to design a 1170 vaccine against SARS-CoV-2 by utilizing multiple antigenic patches from the viral 1171 proteins. The designed MPVs from the antigenic patches of SARS-CoV-2 proteins 1182 have several advantages over to the subunit and multi-epitope based vaccines. Design of multi epitope-based peptide vaccine against E 1409 protein of human 2019-nCoV: An immunoinformatics approach Multi-epitope based peptide 1549 vaccine design against SARS-CoV-2 using its spike protein In silico approach for designing of a multi-epitope based 1587 vaccine against novel Coronavirus (SARS-COV-2) abstract: Background The SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) is a positive-sense single-stranded RNA coronavirus responsible for the ongoing 2019-2020 COVID-19 outbreak. The highly contagious COVID-19 disease has spread to 216 countries in less than six months. Though several vaccine candidates are being claimed, an effective vaccine is yet to come. In present study we have designed and theoretically validated novel Multi-Patch Vaccines against SARS-CoV-2. Methodology A novel reverse epitomics approach, “overlapping-epitope-clusters-to-patches” method is utilized to identify multiple antigenic regions from the SARS-CoV-2 proteome. These antigenic regions are here termed as “Ag-Patch or Ag-Patches”, for Antigenic Patch or Patches. The identification of Ag-Patches is based on clusters of overlapping epitopes rising from a particular region of SARS-CoV-2 protein. Further, we have utilized the identified Ag-Patches to design Multi-Patch Vaccines (MPVs), proposing a novel methodology for vaccine design and development. The designed MPVs were analyzed for immunologically crucial parameters, physiochemical properties and cDNA constructs. Results We identified 73 CTL (Cytotoxic T-Lymphocyte), 49 HTL (Helper T-Lymphocyte) novel Ag-Patches from the proteome of SARS-CoV-2. The identified Ag-Patches utilized to design MPVs cover 768 (518 CTL and 250 HTL) overlapping epitopes targeting different HLA alleles. Such large number of epitope coverage is not possible for multi-epitope vaccines. The large number of epitopes covered implies large number of HLA alleles targeted, and hence large ethnically distributed human population coverage. The MPVs:Toll-Like Receptor ectodomain complex shows stable nature with numerous hydrogen bond formation and acceptable root mean square deviation and fluctuation. Further, the cDNA analysis favors high expression of the MPVs constructs in human cell line. Conclusion Highly immunogenic novel Ag-Patches are identified from the entire proteome of SARS CoV-2 by a novel reverse epitomics approach. We conclude that the novel Multi-Patch Vaccines could be a highly potential novel approach to combat SARS-CoV-2, with greater effectiveness, high specificity and large human population coverage worldwide. ABSTRACT FIGURE: A Multi-Patch Vaccine design to combat SARS-CoV-2 and a method to prepare thereof. Multi-Patch Vaccine designing to combat SARS-CoV-2 infection by reverse epitomics approach, “Overlapping-epitope-clusters-to-patches” method. url: https://doi.org/10.1101/2020.09.06.284992 doi: 10.1101/2020.09.06.284992 id: cord-261961-u4d0vvmq author: St-Germain, Jonathan R. title: A SARS-CoV-2 BioID-based virus-host membrane protein interactome and virus peptide compendium: new proteomics resources for COVID-19 research date: 2020-08-28 words: 2735.0 sentences: 147.0 pages: flesch: 41.0 cache: ./cache/cord-261961-u4d0vvmq.txt txt: ./txt/cord-261961-u4d0vvmq.txt summary: To this end, we conducted a mass spectrometry-based characterization of the SARS-CoV-2 virion and infected cell lysates, identifying 189 unique high-confidence virus tryptic peptides derived from 17 different virus proteins, to create a high quality resource for use in targeted proteomics approaches. The resulting viral tryptic peptides were identified using nanoflow liquid chromatography -tandem mass spectrometry (LC-MS/MS; Fig 1A, Together, these data confirm and expand upon previous proteomic analyses of SARS-CoV-2 virions, infected cells 4, 7-11 and patient samples [12] [13] [14] , and provide a library of high quality virus peptide spectra covering 17 virus proteins that can be used for the creation of peptide spectral libraries and targeted proteomics approaches. To this end, we also undertook an analysis of SARS-CoV-2 virions and infected Vero cell lsyates using data-dependent acquisition tandem mass spectrometry, and identified 189 unique tryptic peptides, assigned to 17 different virus proteins. abstract: Key steps of viral replication take place at host cell membranes, but the detection of membrane-associated protein-protein interactions using standard affinity-based approaches (e.g. immunoprecipitation coupled with mass spectrometry, IP-MS) is challenging. To learn more about SARS-CoV-2 - host protein interactions that take place at membranes, we utilized a complementary technique, proximity-dependent biotin labeling (BioID). This approach uncovered a virus-host topology network comprising 3566 proximity interactions amongst 1010 host proteins, highlighting extensive virus protein crosstalk with: (i) host protein folding and modification machinery; (ii) membrane-bound vesicles and organelles, and; (iii) lipid trafficking pathways and ER-organelle membrane contact sites. The design and implementation of sensitive mass spectrometric approaches for the analysis of complex biological samples is also important for both clinical and basic research proteomics focused on the study of COVID-19. To this end, we conducted a mass spectrometry-based characterization of the SARS-CoV-2 virion and infected cell lysates, identifying 189 unique high-confidence virus tryptic peptides derived from 17 different virus proteins, to create a high quality resource for use in targeted proteomics approaches. Together, these datasets comprise a valuable resource for MS-based SARS-CoV-2 research, and identify novel virus-host protein interactions that could be targeted in COVID-19 therapeutics. url: https://doi.org/10.1101/2020.08.28.269175 doi: 10.1101/2020.08.28.269175 id: cord-342942-1s32o9m8 author: Stamatakis, George title: Generation of SARS-CoV-2 S1 spike glycoprotein putative antigenic epitopes in vitro by intracellular aminopeptidases date: 2020-06-22 words: 4074.0 sentences: 209.0 pages: flesch: 47.0 cache: ./cache/cord-342942-1s32o9m8.txt txt: ./txt/cord-342942-1s32o9m8.txt summary: Here, we analyzed the proteolytic processing of overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes that generate antigenic peptides, aminopeptidases ERAP1, ERAP2 and IRAP. In this study, we utilized a novel approach to analyze antigen trimming by intracellular aminopeptidases ERAP1, ERAP2 and IRAP, focusing on the largest antigen of SARS-CoV-2, namely S1 spike glycoprotein. To investigate the trimming of antigenic epitope precursors by intracellular aminopeptidases that generate antigenic peptides, we used a mixture of 315 synthetic peptides derived from the sequence of the SARS-CoV-2 S1 spike glycoprotein. Our analysis of the largest antigen of SARS-CoV-2, S1 spike glycoprotein, suggests that aminopeptidase trimming can be a significant filter that helps shape which peptides will be presented by HLA. abstract: Presentation of antigenic peptides by MHCI is central to cellular immune responses against viral pathogens. While adaptive immune responses versus SARS-CoV-2 can be of critical importance to both recovery and vaccine efficacy, how protein antigens from this pathogen are processed to generate antigenic peptides is largely unknown. Here, we analyzed the proteolytic processing of overlapping precursor peptides spanning the entire sequence of the S1 spike glycoprotein of SARS-CoV-2, by three key enzymes that generate antigenic peptides, aminopeptidases ERAP1, ERAP2 and IRAP. All enzymes generated shorter peptides with sequences suitable for binding onto HLA alleles, but with distinct specificity fingerprints. ERAP1 was the most efficient in generating peptides 8-11 residues long, the optimal length for HLA binding, while IRAP was the least efficient. The combination of ERAP1 with ERAP2 greatly limited the variability of peptide sequences produced. Less than 7% of computationally predicted epitopes were found to be produced experimentally, suggesting that aminopeptidase processing may constitute a significant filter to epitope presentation. These experimentally generated putative epitopes could be prioritized for SARS-CoV-2 immunogenicity studies and vaccine design. We furthermore propose that this in vitro trimming approach could constitute a general filtering method to enhance the prediction robustness for viral antigenic epitopes. url: https://doi.org/10.1101/2020.06.22.164681 doi: 10.1101/2020.06.22.164681 id: cord-275690-83nrzfon author: Stanifer, Megan L. title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells date: 2020-04-24 words: 4696.0 sentences: 256.0 pages: flesch: 52.0 cache: ./cache/cord-275690-83nrzfon.txt txt: ./txt/cord-275690-83nrzfon.txt summary: title: Critical role of type III interferon in controlling SARS-CoV-2 infection, replication and spread in primary human intestinal epithelial cells Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, and in agreement with the results observed in cells depleted of the type III IFN receptor, this increase in infectivity was also associated with an increase in infectious denovo virus particle production ( Fig. 3G ). All together, these results strongly support a model where the type III IFN mediated signaling controls SARS-CoV-2 infection in human intestinal epithelial cells. All together these results show that human colon organoids can support SARS-CoV-2 infection, replication and spread and that the type III IFN response plays a critical role in controlling virus replication. abstract: SARS-CoV-2 is an unprecedented worldwide health problem that requires concerted and global approaches to better understand the virus in order to develop novel therapeutic approaches to stop the COVID-19 pandemic and to better prepare against potential future emergence of novel pandemic viruses. Although SARS-CoV-2 primarily targets cells of the lung epithelium causing respiratory infection and pathologies, there is growing evidence that the intestinal epithelium is also infected. However, the importance of the enteric phase of SARS-CoV-2 for virus-induced pathologies, spreading and prognosis remains unknown. Here, using both colon-derived cell lines and primary non-transformed colon organoids, we engage in the first comprehensive analysis of SARS-CoV-2 lifecycle in human intestinal epithelial cells. Our results demonstrate that human intestinal epithelial cells fully support SARS-CoV-2 infection, replication and production of infectious de-novo virus particles. Importantly, we identified intestinal epithelial cells as the best culture model to propagate SARS-CoV-2. We found that viral infection elicited an extremely robust intrinsic immune response where, interestingly, type III interferon mediated response was significantly more efficient at controlling SARS-CoV-2 replication and spread compared to type I interferon. Taken together, our data demonstrate that human intestinal epithelial cells are a productive site of SARS-CoV-2 replication and suggest that the enteric phase of SARS-CoV-2 may participate in the pathologies observed in COVID-19 patients by contributing in increasing patient viremia and by fueling an exacerbated cytokine response. url: https://doi.org/10.1101/2020.04.24.059667 doi: 10.1101/2020.04.24.059667 id: cord-303868-aes92l6s author: Steffen, Tara L. title: The receptor binding domain of SARS-CoV-2 spike is the key target of neutralizing antibody in human polyclonal sera date: 2020-08-22 words: 6098.0 sentences: 300.0 pages: flesch: 46.0 cache: ./cache/cord-303868-aes92l6s.txt txt: ./txt/cord-303868-aes92l6s.txt summary: In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. This suggests that polyclonal antibody binding to the RBD domain of the spike protein represents the key target of neutralizing antibody to SARS-CoV-2 after natural infection. Most importantly, our antigen-specific antibody depletion approach demonstrated that the RBD domain of the spike protein is responsible for 70% +/-18.9% of the human polyclonal neutralizing antibody activity to spike after natural SARS-CoV-2 infection. Although our study shows that the dominant target of IgG neutralizing antibody response after natural SARS-CoV-2 infection is the RBD domain of the spike protein, we have evaluated a limited number (n=10) of patients by antigen-specific antibody depletion. abstract: Natural infection of SARS-CoV-2 in humans leads to the development of a strong neutralizing antibody response, however the immunodominant targets of the polyclonal neutralizing antibody response are still unknown. Here, we functionally define the role SARS-CoV-2 spike plays as a target of the human neutralizing antibody response. In this study, we identify the spike protein subunits that contain antigenic determinants and examine the neutralization capacity of polyclonal sera from a cohort of patients that tested qRT-PCR-positive for SARS-CoV-2. Using an ELISA format, we assessed binding of human sera to spike subunit 1 (S1), spike subunit 2 (S2) and the receptor binding domain (RBD) of spike. To functionally identify the key target of neutralizing antibody, we depleted sera of subunit-specific antibodies to determine the contribution of these individual subunits to the antigen-specific neutralizing antibody response. We show that epitopes within RBD are the target of a majority of the neutralizing antibodies in the human polyclonal antibody response. These data provide critical information for vaccine development and development of sensitive and specific serological testing. url: https://doi.org/10.1101/2020.08.21.261727 doi: 10.1101/2020.08.21.261727 id: cord-353209-qkhfp66l author: Steiner, Daniel J. title: Array-based analysis of SARS-CoV-2, other coronaviruses, and influenza antibodies in convalescent COVID-19 patients date: 2020-06-16 words: 2517.0 sentences: 129.0 pages: flesch: 45.0 cache: ./cache/cord-353209-qkhfp66l.txt txt: ./txt/cord-353209-qkhfp66l.txt summary: We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. Aminereactive substrates for fabrication of AIR arrays were provided by Adarza BioSystems, Inc. For ELISA assays, SARS-CoV-2 full-length spike and RBD were produced in-house using a mammalian expression system, 20,21 as was influenza A/H1N1/California 2009 hemagglutinin. To that end, we have presented preliminary data on a 15-plex array on the AIR platform, developed in response to the need to study SARS-CoV-2 but incorporating antigens for other coronaviruses and influenza. Responses to SARS-CoV-2 antigens on the array effectively discriminated between serum samples from uninfected and COVID-19 convalescent subjects, with generally good correlation to ELISA data. abstract: Detection of antibodies to upper respiratory pathogens is critical to surveillance, assessment of the immune status of individuals, vaccine development, and basic biology. The urgent need for antibody detection tools has proven particularly acute in the COVID-19 era. We report a multiplex label-free antigen microarray on the Arrayed Imaging Reflectometry (AIR) platform for detection of antibodies to SARS-CoV-2, SARS-CoV-1, MERS, three circulating coronavirus strains (HKU1, 229E, OC43) and three strains of influenza. We find that the array is readily able to distinguish uninfected from convalescent COVID-19 subjects, and provides quantitative information about total Ig, as well as IgG- and IgM-specific responses. url: https://doi.org/10.1101/2020.06.15.153064 doi: 10.1101/2020.06.15.153064 id: cord-305496-t8ykkekl author: Stone, E. Taylor title: Characterization of cells susceptible to SARS-COV-2 and methods for detection of neutralizing antibody by focus forming assay date: 2020-08-21 words: 7227.0 sentences: 391.0 pages: flesch: 60.0 cache: ./cache/cord-305496-t8ykkekl.txt txt: ./txt/cord-305496-t8ykkekl.txt summary: One such tool for evaluating neutralizing antibody response is a 88 plaque/focus neutralization reduction test (PRNT/FRNT), which evaluates the ability of polyclonal 89 sera samples to prevent or reduce infection of a cell monolayer in vitro. We examined the impact of cell density on foci formation for both Vero WHO and Vero E6 cells 144 by plating identical dilutions of SARS-CoV-2 virus stocks on 96-well plates seeded with differing 145 numbers of WHO or E6 cells (3 × 104, 1.5 × 104 or 3 × 104 cells/well) one day prior to infection 146 of the cell monolayer. To determine the optimal time frame for infection of SARS-CoV-2 on a Vero WHO cell 172 monolayer to form individual foci, we tested a variety of incubation times. The FFA relies on an immunostaining protocol of an infected cell monolayer in order to 197 quantify infectious virus titer and is therefore dependent upon SARS-CoV-2-specific antibody 198 abstract: The SARS-CoV-2 outbreak and subsequent COVID-19 pandemic have highlighted the urgent need to determine what cells are susceptible to infection and for assays to detect and quantify SARS-CoV-2. Furthermore, the ongoing efforts for vaccine development have necessitated the development of rapid, high-throughput methods of quantifying infectious SARS-CoV-2, as well as the ability to screen human polyclonal sera samples for neutralizing antibodies against SARS-CoV-2. To this end, our lab has adapted focus forming assays for SARS-CoV-2 using Vero CCL-81 cells, referred to in this text as Vero WHO. Using the focus forming assay as the basis for screening cell susceptibility and to develop a focus reduction neutralization test. We have shown that this assay is a sensitive tool for determining SARS-CoV-2 neutralizing antibody titer in human, non-human primate, and mouse polyclonal sera following SARS-CoV-2 exposure. Additionally, we describe the viral growth kinetics of SARS-CoV-2 in a variety of different immortalized cell lines and demonstrate via human ACE2 and viral spike protein expression that these cell lines can support viral entry and replication. url: https://doi.org/10.1101/2020.08.20.259838 doi: 10.1101/2020.08.20.259838 id: cord-303399-s1hbpvn7 author: Straus, Marco R. title: SPINT2 inhibits proteases involved in activation of both influenza viruses and metapneumoviruses date: 2019-08-31 words: 6424.0 sentences: 466.0 pages: flesch: 64.0 cache: ./cache/cord-303399-s1hbpvn7.txt txt: ./txt/cord-303399-s1hbpvn7.txt summary: SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. https://doi.org/10.1101/752592 doi: bioRxiv preprint vivo situation and requires validation by expressing the full-length fusion proteins in a cell culture model 3 to test cleavage and cleavage inhibition of the respective protease (39). To test SPINT2-mediated cleavage inhibition of full-length HA we expressed the HAs of A/CA/04/09 9 (H1N1), A/x31 (H3N2) and A/Shanghai/2/2013 (H7N9) in 293T cells and added recombinant matriptase or 10 KLK5 protease that were pre-incubated with 10nM or 500nM SPINT2. To understand whether SPINT2 was able to inhibit or reduce the growth of virus in a cell culture 20 model over the course of 48 hours we transfected cells with human TMPRSS2 and human matriptase, two 21 major proteases that have been shown to be responsible for the activation of distinct influenza A subtype 22 abstract: Viruses possessing class I fusion proteins require proteolytic activation by host cell proteases to mediate fusion with the host cell membrane. The mammalian SPINT2 gene encodes a protease inhibitor that targets trypsin-like serine proteases. Here we show the protease inhibitor, SPINT2, restricts cleavage-activation efficiently for a range of influenza viruses and for human metapneumovirus (HMPV). SPINT2 treatment resulted in the cleavage and fusion inhibition of full-length influenza A/CA/04/09 (H1N1) HA, A/Aichi/68 (H3N2) HA, A/Shanghai/2/2013 (H7N9) HA and HMPV F when activated by trypsin, recombinant matriptase or KLK5. We also demonstrate that SPINT2 was able to reduce viral growth of influenza A/CA/04/09 H1N1 and A/X31 H3N2 in cell culture by inhibiting matriptase or TMPRSS2. Moreover, inhibition efficacy did not differ whether SPINT2 was added at the time of infection or 24 hours post-infection. Our data suggest that the SPINT2 inhibitor has a strong potential to serve as a novel broad-spectrum antiviral. url: https://doi.org/10.1101/752592 doi: 10.1101/752592 id: cord-346532-4xpnd93d author: Strömich, Léonie title: Allosteric Hotspots in the Main Protease of SARS-CoV-2 date: 2020-11-06 words: 2370.0 sentences: 145.0 pages: flesch: 60.0 cache: ./cache/cord-346532-4xpnd93d.txt txt: ./txt/cord-346532-4xpnd93d.txt summary: Here, we report the allosteric communication pathways in the main protease dimer by using two novel fully atomistic graph theoretical methods: Bond-to-bond propensity analysis, which has been previously successful in identifying allosteric sites without a priori knowledge in benchmark data sets, and, Markov transient analysis, which has previously aided in finding novel drug targets in catalytic protein families. Bond-to-bond propensities have been shown to successfully detect allosteric sites on proteins [43] and we here present 141 the results in the SARS-CoV-2 M pro to that effect. After a full Bond-to-bond propensity analysis and quantile regression to rank all residues, we are able to score the active 156 site to obtain a measure for the connectivity towards the catalytic center (Tab. S8). A complementary, node-based method, Markov Transient analysis (MTA) 276 identifies areas of the protein that are significantly connected to a site of interest, the source, such as the active site, and 277 obtains the signal propagation that connects the two sites at the atomistic level. abstract: Inhibiting the main protease of SARS-CoV-2 is of great interest in tackling the COVID-19 pandemic caused by the virus. Most efforts have been centred on inhibiting the binding site of the enzyme. However, considering allosteric sites, distant from the active or orthosteric site, broadens the search space for drug candidates and confers the advantages of allosteric drug targeting. Here, we report the allosteric communication pathways in the main protease dimer by using two novel fully atomistic graph theoretical methods: Bond-to-bond propensity analysis, which has been previously successful in identifying allosteric sites without a priori knowledge in benchmark data sets, and, Markov transient analysis, which has previously aided in finding novel drug targets in catalytic protein families. We further score the highest ranking sites against random sites in similar distances through statistical bootstrapping and identify four statistically significant putative allosteric sites as good candidates for alternative drug targeting. url: https://doi.org/10.1101/2020.11.06.369439 doi: 10.1101/2020.11.06.369439 id: cord-291710-ixun0c8g author: Su, Haixia title: Discovery of baicalin and baicalein as novel, natural product inhibitors of SARS-CoV-2 3CL protease in vitro date: 2020-04-14 words: 2572.0 sentences: 154.0 pages: flesch: 53.0 cache: ./cache/cord-291710-ixun0c8g.txt txt: ./txt/cord-291710-ixun0c8g.txt summary: A crystal structure of SARS-CoV-2 3CLpro in complex with baicalein, the first non-covalent, non-peptidomimetic small-molecule inhibitor, was also determined, revealing a unique binding mode of this natural product with the protease. To validate the binding of baicalin and baicalein with SARS-CoV-2 3CLpro and exclude the suspicion of being the pan-assay interference compounds (PAINS) (15) , their binding affinities with the protease were measured by isothermal titration calorimetry (ITC), widely known as an invaluable tool used to determine thermodynamic parameters of protein-ligand interactions such as Kd (Fig. 1, A and B ; Table 1 ). Moreover, the ITC profiles in combination with their chemical structures suggest that baicalin and baicalein act as noncovalent inhibitors of SARS-CoV-2 3CLpro with a high ligand binding efficiency. The mode of action of baicalein and the structural determinants associated with its binding with SARS-CoV-2 3CLpro were further explored using X-ray protein crystallography. abstract: Human infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause coronavirus disease 19 (COVID-19) and there is currently no cure. The 3C-like protease (3CLpro), a highly conserved protease indispensable for replication of coronaviruses, is a promising target for development of broad-spectrum antiviral drugs. To advance the speed of drug discovery and development, we investigated the inhibition of SARS-CoV-2 3CLpro by natural products derived from Chinese traditional medicines. Baicalin and baicalein were identified as the first non-covalent, non-peptidomimetic inhibitors of SARS-CoV-2 3CLpro and exhibited potent antiviral activities in a cell-based system. Remarkably, the binding mode of baicalein with SARS-CoV-2 3CLpro determined by X-ray protein crystallography is distinctly different from those of known inhibitors. Baicalein is perfectly ensconced in the core of the substrate-binding pocket by interacting with two catalytic residues, the crucial S1/S2 subsites and the oxyanion loop, acting as a “shield” in front of the catalytic dyad to prevent the peptide substrate approaching the active site. The simple chemical structure, unique mode of action, and potent antiviral activities in vitro, coupled with the favorable safety data from clinical trials, emphasize that baicalein provides a great opportunity for the development of critically needed anti-coronaviral drugs. url: https://doi.org/10.1101/2020.04.13.038687 doi: 10.1101/2020.04.13.038687 id: cord-103046-w8bm4p44 author: Suarez, David L. title: Lack of susceptibility of poultry to SARS-CoV-2 and MERS-CoV date: 2020-06-16 words: 565.0 sentences: 44.0 pages: flesch: 58.0 cache: ./cache/cord-103046-w8bm4p44.txt txt: ./txt/cord-103046-w8bm4p44.txt summary: Multiple studies have examined the susceptibility of domestic animals to CoV-2 to establish the risk of zoonotic transmission and two studies have shown chickens and 24 Middle East Respiratory Syndrome coronavirus (MERS-CoV), another coronavirus of 26 high concern associated with zoonotic infection, was first detected in patients with severe acute 27 lower respiratory tract disease in Saudi Arabia in 2012. For MERS-CoV, dromedary 35 camels appear to be the primary natural reservoir of infection to humans, but other domestic 36 animals seem to be susceptible to infection (7, 8) . Because poultry are so widespread and have close and extended contact with humans, 39 and other mammals in many production systems, including live animal markets, susceptibility 40 were conducted with SARS-CoV-2 and MERS-CoV in five common poultry species. Susceptibility of ferrets, cats, 109 dogs, and other domesticated animals to SARS-coronavirus 2. Middle East Respiratory Syndrome (MERS), and SARS-114 Middle East 118 respiratory syndrome coronavirus infection in non-camelid domestic mammals. abstract: Chickens, turkeys, ducks, quail and geese were challenged with SARS-CoV-2 or MERS-CoV. No disease was observed, no virus replication was detected, and antibodies were not detected in serum. Neither virus replicated in embryonating chicken’s eggs. Poultry are unlikely to serve a role in the maintenance of either virus. url: https://doi.org/10.1101/2020.06.16.154658 doi: 10.1101/2020.06.16.154658 id: cord-319447-xanewi59 author: Sun, Jiya title: Comparative transcriptome analysis reveals the intensive early-stage responses of host cells to SARS-CoV-2 infection date: 2020-05-01 words: 3250.0 sentences: 163.0 pages: flesch: 52.0 cache: ./cache/cord-319447-xanewi59.txt txt: ./txt/cord-319447-xanewi59.txt summary: To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. In this study, we used the SARS-CoV-2 strain isolated from patients [11] to infect in vitro Calu-3 cells, and performed RNA sequencing to determine the time-series transcriptome profiling data of the host. Next, to gain possible explanations for the distinct patterns in host antiviral capacity and cytokine production during SARS-CoV-2 infection, dynamic expression of four types of key genes were evaluated, including virus receptors for cell entry, pathogen recognition receptors (PRRs) for an innate immune startup, regulator genes for induction of antiviral-related genes and interferon production (Figure 4) . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a widespread outbreak of highly pathogenic COVID-19. It is therefore important and timely to characterize interactions between the virus and host cell at the molecular level to understand its disease pathogenesis. To gain insights, we performed high-throughput sequencing that generated time-series data simultaneously for bioinformatics analysis of virus genomes and host transcriptomes implicated in SARS-CoV-2 infection. Our analysis results showed that the rapid growth of the virus was accompanied by an early intensive response of host genes. We also systematically compared the molecular footprints of the host cells in response to SARS-CoV-2, SARS-CoV and MERS-CoV. Upon infection, SARS-CoV-2 induced hundreds of up-regulated host genes hallmarked by a significant cytokine production followed by virus-specific host antiviral responses. While the cytokine and antiviral responses triggered by SARS-CoV and MERS-CoV were only observed during the late stage of infection, the host antiviral responses during the SARS-CoV-2 infection were gradually enhanced lagging behind the production of cytokine. The early rapid host responses were potentially attributed to the high efficiency of SARS-CoV-2 entry into host cells, underscored by evidence of a remarkably up-regulated gene expression of TPRMSS2 soon after infection. Taken together, our findings provide novel molecular insights into the mechanisms underlying the infectivity and pathogenicity of SARS-CoV-2. url: https://doi.org/10.1101/2020.04.30.071274 doi: 10.1101/2020.04.30.071274 id: cord-312305-ll29frwc author: Sun, Shihui title: Characterization and structural basis of a lethal mouse-adapted SARS-CoV-2 date: 2020-11-11 words: 4720.0 sentences: 270.0 pages: flesch: 52.0 cache: ./cache/cord-312305-ll29frwc.txt txt: ./txt/cord-312305-ll29frwc.txt summary: Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. We further characterized the in vivo replication dynamics of MASCp6 in both young and aged mice, and the results from qRT-PCR showed that high levels of SARS-CoV-2 subgenomic RNAs were persistent in the lung and tracheas till 4 day post infection (dpi) in aged mice (Fig. 1E) . The skewed age distribution of COVID-19 disease was reproduced in the MASCp36 infected mouse model where more severe symptoms were observed in aged mice when compared to young mice. In addition to the age-related skewed distribution of COVID-19, gender-related differences in distribution of COVID-19 disease is also recapitulated in this MASCp36 infected mouse model with increased susceptibility and enhanced pathogenicity observed in male mice when compared to their female counterparts. abstract: The ongoing SARS-CoV-2 pandemic has brought an urgent need for animal models to study the pathogenicity of the virus. Herein, we generated and characterized a novel mouse-adapted SARS-CoV-2 strain named MASCp36 that causes acute respiratory symptoms and mortality in standard laboratory mice. Particularly, this model exhibits age and gender related skewed distribution of mortality akin to severe COVID-19, and the 50% lethal dose (LD50) of MASCp36 was ∼100 PFU in aged, male BALB/c mice. Deep sequencing identified three amino acid mutations, N501Y, Q493H, and K417N, subsequently emerged at the receptor binding domain (RBD) of MASCp36, which significantly enhanced the binding affinity to its endogenous receptor, mouse ACE2 (mACE2). Cryo-electron microscopy (cryo-EM) analysis of mACE2 in complex with the RBD of MASCp36 at 3.7-angstrom resolution elucidates molecular basis for the receptor-binding switch driven by amino acid substitutions. Our study not only provides a robust platform for studying the pathogenesis of severe COVID-19 and rapid evaluation of coutermeasures against SARS-CoV-2, but also unveils the molecular mechanism for the rapid adaption and evolution of SARS-CoV-2 in mice. One sentence summary A mouse adapted SARS-CoV-2 strain that harbored three amino acid substitutions in the RBD of S protein showed 100% mortality in aged, male BALB/c mice. url: https://doi.org/10.1101/2020.11.10.377333 doi: 10.1101/2020.11.10.377333 id: cord-326666-melz5fq4 author: Sun, Weitao title: The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe date: 2020-09-03 words: 1723.0 sentences: 138.0 pages: flesch: 62.0 cache: ./cache/cord-326666-melz5fq4.txt txt: ./txt/cord-326666-melz5fq4.txt summary: title: The discovery of gene mutations making SARS-CoV-2 well adapted for humans: host-genome similarity analysis of 2594 genomes from China, the USA and Europe This study shows that the host-genome similarity (HGS) of SARS-CoV-2 is significantly higher than that of SARS-CoV, especially in the ORF6 and ORF8 genes encoding proteins antagonizing innate immunity in vivo. This finding implies that high HGS of SARS-CoV-2 genome may further inhibit IFN I synthesis and cause delayed host innate immunity. An ORF1ab mutation, 10818G>T, which occurred in virus populations with high HGS but rarely in low-HGS populations, was identified in 2594 genomes with geolocations of China, the USA and Europe. 578 shown with special markers at the top of colored blocks representing ORFs. Mutation 623 10818G>T in ORF1ab (codon TTG>TTT) occurred in populations with high HGS, which 624 results in amino acid M37F mutation in transmembrane protein nsp6. ORF1ab (codon TTG>TTT) occurred in populations with high HGS, which results in amino 631 acid M37F mutation in transmembrane protein nsp6. abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense single-stranded virus approximately 30 kb in length, causes the ongoing novel coronavirus disease-2019 (COVID-19). Studies confirmed significant genome differences between SARS-CoV-2 and SARS-CoV, suggesting that the distinctions in pathogenicity might be related to genomic diversity. However, the relationship between genomic differences and SARS-CoV-2 fitness has not been fully explained, especially for open reading frame (ORF)-encoded accessory proteins. RNA viruses have a high mutation rate, but how SARS-CoV-2 mutations accelerate adaptation is not clear. This study shows that the host-genome similarity (HGS) of SARS-CoV-2 is significantly higher than that of SARS-CoV, especially in the ORF6 and ORF8 genes encoding proteins antagonizing innate immunity in vivo. A power law relationship was discovered between the HGS of ORF3b, ORF6, and N and the expression of interferon (IFN)-sensitive response element (ISRE)-containing promoters. This finding implies that high HGS of SARS-CoV-2 genome may further inhibit IFN I synthesis and cause delayed host innate immunity. An ORF1ab mutation, 10818G>T, which occurred in virus populations with high HGS but rarely in low-HGS populations, was identified in 2594 genomes with geolocations of China, the USA and Europe. The 10818G>T caused the amino acid mutation M37F in the transmembrane protein nsp6. The results suggest that the ORF6 and ORF8 genes and the mutation M37F may play important roles in causing COVID-19. The findings demonstrate that HGS analysis is a promising way to identify important genes and mutations in adaptive strains, which may help in searching potential targets for pharmaceutical agents. url: https://doi.org/10.1101/2020.09.03.280727 doi: 10.1101/2020.09.03.280727 id: cord-102808-c7ajfvt5 author: Sundqvist, Martina title: Barbadin selectively modulates FPR2-mediated neutrophil functions independent of receptor endocytosis date: 2020-05-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Formyl peptide receptor 2 (FPR2), a member of the family of G protein-coupled receptors (GPCRs), mediates neutrophil migration, a response that has been linked to β-arrestin recruitment. β-Arrestin regulates GPCR endocytosis and can also elicit non-canonical receptor signaling. To determine the poorly understood role of β-arrestin in FPR2 endocytosis and in NADPH-oxidase activation in neutrophils, Barbadin was used as a research tool in this study. Barbadin has been shown to bind the clathrin adaptor protein (AP2) and thereby prevent β- arrestin/AP2 interaction and β-arrestin-mediated GPCR endocytosis. In agreement with this, AP2/β-arrestin interaction induced by an FPR2-specific agonist was inhibited by Barbadin. Unexpectedly, however, Barbadin did not inhibit FPR2 endocytosis, indicating that a mechanism independent of β-arrestin/AP2 interaction may sustain FPR2 endocytosis. This was confirmed by the fact, that FPR2 also underwent agonist-promoted endocytosis in β-arrestin deficient cells, albeit at a diminished level as compared to wild type cells. Dissection of the Barbadin effects on FPR2-mediated neutrophil functions including NADPH-oxidase activation mediated release of reactive oxygen species (ROS) and chemotaxis reveled that Barbadin had no effect on chemotactic migration whereas the release of ROS was potentiated/primed. The effect of Barbadin on ROS production was reversible, independent of β-arrestin recruitment, and similar to that induced by latrunculin A. Taken together, our data demonstrate that endocytic uptake of FPR2 occurs independently of β-arrestin, while Barbadin selectively augments FPR2-mediated neutrophil ROS production independently of receptor endocytosis. Given that Barbadin binds to AP2 and prevents the AP2/β-arrestin interaction, our results indicate a role for AP2 in FPR2-mediated ROS release from human neutrophils. url: https://doi.org/10.1101/2020.04.30.070011 doi: 10.1101/2020.04.30.070011 id: cord-341768-k86gsfng author: Suresh, Voddu title: Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies date: 2020-06-29 words: 2541.0 sentences: 141.0 pages: flesch: 45.0 cache: ./cache/cord-341768-k86gsfng.txt txt: ./txt/cord-341768-k86gsfng.txt summary: title: Tissue distribution of ACE2 protein in Syrian golden hamster (Mesocricetus auratus) and its possible implications in SARS-CoV-2 related studies The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin□converting enzyme 2 (ACE2), a proven functional receptor for SARS-CoV-2 in different organs of the hamster. Certain earlier studies have shown expression of ACE2 transcripts or protein by lung epithelial cells [15] [16] [17] [18] , hence, just after the reports that ACE2 binds with SARS-CoV-2 spike (S) protein, the research and clinical communities assumed that high level of ACE2 expression in lung or other part of the respiratory tract might be a major driving factor in the pathogenesis of this respiratory virus. High expression of ACE2 in the kidney is believed to contribute to SARS-CoV-2 virus pathogenesis and disease severity 22 In our analysis, in addition to kidney and different parts of the gut, brain, liver, tongue are three other extra-pulmonary organs that showed ACE2 expression (Figure 1, 3 & 4) . abstract: Recently, the Syrian golden hamster (Mesocricetus auratus) has been demonstrated as a clinically relevant animal model for SARS-CoV-2 infection. However, lack of knowledge about the tissue-specific expression pattern of various proteins in these animals and the unavailability of reagents like antibodies against this species hampers optimal use of these models. The major objective of our current study was to analyze the tissue-specific expression pattern of angiotensin□converting enzyme 2 (ACE2), a proven functional receptor for SARS-CoV-2 in different organs of the hamster. We have adapted immunoblot analysis, immunohistochemistry, and immunofluorescence analysis techniques to evaluate the ACE2 expression pattern in different tissues of the Syrian golden hamster. We found that kidney, small intestine, esophagus, tongue, brain, and liver express ACE2. Epithelium of proximal tubules of kidney and surface epithelium of ileum expresses a very high amount of this protein. Surprisingly, analysis of stained tissue sections for ACE2 showed no detectable expression of ACE2 in the lung or tracheal epithelial cells. Similarly, all parts of the large intestine (caecum, colon, and rectum) were negative for ACE2 expression. Together, our findings corroborate some of the earlier reports related to ACE2 expression pattern in human tissues and also contradicts some others. We believe that the findings of this study will enable the appropriate use of the Syrian golden hamster to carryout SARS-CoV-2 related studies. url: https://doi.org/10.1101/2020.06.29.177154 doi: 10.1101/2020.06.29.177154 id: cord-313805-6mnclfeg author: Suzuki, Yuichiro J. title: SARS-CoV-2 spike protein-mediated cell signaling in lung vascular cells date: 2020-10-12 words: 2299.0 sentences: 128.0 pages: flesch: 56.0 cache: ./cache/cord-313805-6mnclfeg.txt txt: ./txt/cord-313805-6mnclfeg.txt summary: Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. The treatment of human pulmonary artery smooth muscle cells or human pulmonary artery endothelial cells with recombinant SARS-CoV-2 spike protein S1 subunit (Val16 – Gln690) at 10 ng/ml (0.13 nM) caused an activation of MEK phosphorylation. Our results showing that SARS-CoV-2 spike protein is capable of activating the MEK/ERK pathway in pulmonary artery smooth muscle and endothelial cells suggest that cell growth signaling may be triggered in the pulmonary vascular walls in response to SARS-CoV-2. The major finding of this study is that the SARS-CoV-2 spike protein without the rest of the virus can elicit cell signaling, specifically the activation of the MEK/ERK pathway, in human host lung vascular smooth muscle and endothelial cells. abstract: Currently, the world is suffering from the pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses angiotensin-converting enzyme 2 (ACE2) as a receptor to enter the host cells. So far, 30 million people have been infected with SARS-CoV-2, and nearly 1 million people have died because of COVID-19 worldwide, causing serious health, economical, and sociological problems. However, the mechanism of the effect of SARS-CoV-2 on human host cells has not been defined. The present study reports that the SARS-CoV-2 spike protein alone without the rest of the viral components is sufficient to elicit cell signaling in lung vascular cells. The treatment of human pulmonary artery smooth muscle cells or human pulmonary artery endothelial cells with recombinant SARS-CoV-2 spike protein S1 subunit (Val16 – Gln690) at 10 ng/ml (0.13 nM) caused an activation of MEK phosphorylation. The activation kinetics was transient with a peak at 10 min. The recombinant protein that contains only the ACE2 receptor-binding domain of SARS-CoV-2 spike protein S1 subunit (Arg319 – Phe541), on the other hand, did not cause this activation. Consistent with the activation of cell growth signaling in lung vascular cells by SARS-CoV-2 spike protein, pulmonary vascular walls were found to be thickened in COVID-19 patients. Thus, SARS-CoV-2 spike protein-mediated cell growth signaling may participate in adverse cardiovascular/pulmonary outcomes, and this mechanism may provide new therapeutic targets to combat COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33052333/ doi: 10.1101/2020.10.12.335083 id: cord-327912-wfjdxgxh author: Swann, Heather title: Minimal system for assembly of SARS-CoV-2 virus like particles date: 2020-08-24 words: 1695.0 sentences: 98.0 pages: flesch: 59.0 cache: ./cache/cord-327912-wfjdxgxh.txt txt: ./txt/cord-327912-wfjdxgxh.txt summary: Here we demonstrate that non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled by co-expressing the viral proteins S, M and E in mammalian cells. Non-infectious virus like particles (VLPs) displaying essential viral proteins can be used to study the structural properties of the SARS-CoV-2 virions and due to their maximum immunogenicity are also vaccine candidates 2, 3 . Similarly, expression of M, E and S proteins are shown to result in release of morphologically identical particles to wild type SARS-CoV virus 9, 10 . We then tested the structural integrity of the SARS-CoV-2 VLPs attached to dry glass using Atomic Force Microscopy (AFM), since SARS-CoV-2 virions have been reported to survive on solid surfaces in dry conditions for many hours 13 . SARS-CoV-2 M, S and E protein genes were identified from the full genome sequence of the virus 1 , these genes were then humanized and inserted in CMV driven mammalian expression vectors (see supplement for complete plasmid sequences). abstract: SARS-CoV-2 virus is the causative agent of COVID-19. Here we demonstrate that non-infectious SARS-CoV-2 virus like particles (VLPs) can be assembled by co-expressing the viral proteins S, M and E in mammalian cells. The assembled SARS-CoV-2 VLPs possess S protein spikes on particle exterior, making them ideal for vaccine development. The particles range in shape from spherical to elongated with a characteristic size of 129 ± 32 nm. We further show that SARS-CoV-2 VLPs dried in ambient conditions can retain their structural integrity upon repeated scans with Atomic Force Microscopy up to a peak force of 1 nN. url: https://doi.org/10.1101/2020.06.01.128058 doi: 10.1101/2020.06.01.128058 id: cord-102892-nt1zoktv author: Sweeney, Blake A. title: R2DT: computational framework for template-based RNA secondary structure visualisation across non-coding RNA types date: 2020-09-11 words: 3366.0 sentences: 188.0 pages: flesch: 54.0 cache: ./cache/cord-102892-nt1zoktv.txt txt: ./txt/cord-102892-nt1zoktv.txt summary: Consensus tRNA primary 213 sequence with 2D structure for each isotype of each taxonomic domain was generated based 214 on the tRNA alignments used for building the isotype-specific covariance models in tRNAscan-215 SE 2.0 16 . 270 R2DT templates model the conserved core of most structured RNAs We classified each nucleotide in the resulting diagrams according to whether it matched a 282 template and found that 90.6% of nucleotides were displayed using the nucleotide locations 283 encoded in the templates, while 6.0% of nucleotides represented insertions compared to the 284 templates, and 3.4% of nucleotides matched the templates but required automatic repositioning 285 by the Traveler software (Table 2) . In addition, R2DT will benefit from the ongoing development Isotype-specific consensus tRNA sequences and 2D structures were generated using R-scape 52 389 from the alignments that were used to train and build the corresponding covariance models in 390 tRNAscan-SE 16 . abstract: Non-coding RNAs (ncRNA) are essential for all life, and the functions of many ncRNAs depend on their secondary (2D) and tertiary (3D) structure. Despite proliferation of 2D visualisation software, there is a lack of methods for automatically generating 2D representations in consistent, reproducible, and recognisable layouts, making them difficult to construct, compare and analyse. Here we present R2DT, a comprehensive method for visualising a wide range of RNA structures in standardised layouts. R2DT is based on a library of 3,632 templates representing the majority of known structured RNAs, from small RNAs to the large subunit ribosomal RNA. R2DT has been applied to ncRNA sequences from the RNAcentral database and produced >13 million diagrams, creating the world’s largest RNA 2D structure dataset. The software is freely available at https://github.com/rnacentral/R2DT and a web server is found at https://rnacentral.org/r2dt. url: https://doi.org/10.1101/2020.09.10.290924 doi: 10.1101/2020.09.10.290924 id: cord-102451-pcuzylva author: Swoger, Maxx title: Vimentin intermediate filaments mediate cell shape on visco-elastic substrates date: 2020-09-08 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ability of cells to take and change shape is a fundamental feature underlying development, wound repair, and tissue maintenance. Central to this process is physical and signaling interactions between the three cytoskeletal polymeric networks: F-actin, microtubules, and intermediate filaments (IFs). Vimentin is an IF protein that is essential to the mechanical resilience of cells and regulates cross-talk amongst the cytoskeleton, but its role in how cells sense and respond to the surrounding extracellular matrix is largely unclear. To investigate vimentin’s role in substrate sensing, we designed polyacrylamide hydrogels that mimic the elastic and viscoelastic nature of in vivo tissues. Using wild-type and vimentin-null mouse embryonic fibroblasts, we show that vimentin enhances cell spreading on viscoelastic substrates, even though it has little effect in the limit of purely elastic substrates. Our results provide compelling evidence that the vimentin cytoskeletal network is a physical modulator of how cells sense and respond to mechanical properties of their extracellular environment. url: https://doi.org/10.1101/2020.09.07.286237 doi: 10.1101/2020.09.07.286237 id: cord-253987-83h861lp author: Tada, Takuya title: A soluble ACE2 microbody protein fused to a single immunoglobulin Fc domain is a potent inhibitor of SARS-CoV-2 infection in cell culture date: 2020-09-17 words: 6830.0 sentences: 349.0 pages: flesch: 50.0 cache: ./cache/cord-253987-83h861lp.txt txt: ./txt/cord-253987-83h861lp.txt summary: The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. In SARS-CoV-2 entry, the virus attaches to the target cell through the interaction of the spike glycoprotein (S) with its receptor, the angiotensin-converting enzyme 2 (ACE2) (Li, 2015; Li et al., 2005; Li et al., 2003) , a plasma membrane protein carboxypeptidase that degrades angiotensin II to angiotensin-(1-7) [Ang-(1-7)] a vasodilator that promotes sodium transport in the regulation of cardiac function and blood pressure (Kuba et al., 2010; Riordan, 2003; Tikellis and Thomas, 2012) . To determine the relative antiviral activity of soluble ACE2 and the ACE2 microbody proteins, we tested their ability to block the infection SARS-CoV-2 Δ19 S protein pseudotyped GFP/luciferase reporter virus. abstract: Soluble forms of ACE2 have recently been shown to inhibit SARS-CoV-2 infection. We report on an improved soluble ACE2, termed a “microbody” in which the ACE2 ectodomain is fused to Fc domain 3 of the immunoglobulin heavy chain. The protein is smaller than previously described ACE2-Ig Fc fusion proteins and contains an H345A mutation in the ACE2 catalytic active site that inactivates the enzyme without reducing its affinity for the SARS-CoV-2 spike. The disulfide-bonded ACE2 microbody protein inhibited entry of lentiviral SARS-CoV-2 spike protein pseudotyped virus and live SARS-CoV-2 with a potency 10-fold higher than unmodified soluble ACE2 and was active after initial virus binding to the cell. The ACE2 microbody inhibited the entry of ACE2-specific β coronaviruses and viruses with the high infectivity variant D614G spike. The ACE2 microbody may be a valuable therapeutic for COVID-19 that is active against SARS-CoV-2 variants and future coronaviruses that may arise. url: https://doi.org/10.1101/2020.09.16.300319 doi: 10.1101/2020.09.16.300319 id: cord-335118-oa9jfots author: Taka, E. title: Critical Interactions Between the SARS-CoV-2 Spike Glycoprotein and the Human ACE2 Receptor date: 2020-09-21 words: 5264.0 sentences: 344.0 pages: flesch: 61.0 cache: ./cache/cord-335118-oa9jfots.txt txt: ./txt/cord-335118-oa9jfots.txt summary: By performing all-atom Molecular Dynamics (MD) simulations, we identified an extended network of salt bridges, hydrophobic and electrostatic interactions, and hydrogen bonding between the receptor-binding domain (RBD) of the S protein and ACE2. Initial studies have constructed a homology model of SARS-CoV-2 RBD in complex with ACE2, based on the SARS-CoV crystal structure (8, 14) and performed conventional MD (cMD) simulations totaling 10 ns (15, 16) and 100 ns (17, 18) in length to estimate binding free energies (15, 16) and interaction scores (18) . In this study, we performed a comprehensive set of all-atom MD simulations totaling 16.5 µs in length using the recently-solved structure of the RBD of the SARS-CoV-2 S protein in complex with the PD of ACE2 (7) . In 20 SMD simulations (each 15 ns, totaling 300 ns in length, table S1), the average work applied to unbind RBD from PD was 71.1 ± 12.7 kcal/mol (mean ± s.d.), demonstrating that the S protein binds stably to ACE2 (Fig. 3B) . abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters human cells upon binding of its spike (S) glycoproteins to ACE2 receptors and causes the Coronavirus disease 2019 (COVID-19). Therapeutic approaches to prevent SARS-CoV-2 infection are mostly focused on blocking S-ACE2 binding, but critical residues that stabilize this interaction are not well understood. By performing all-atom Molecular Dynamics (MD) simulations, we identified an extended network of salt bridges, hydrophobic and electrostatic interactions, and hydrogen bonding between the receptor-binding domain (RBD) of the S protein and ACE2. Mutagenesis of these residues on the RBD was not sufficient to destabilize binding but reduced the average work to unbind the S protein from ACE2. In particular, the hydrophobic end of RBD serves as the main anchor site and unbinds last from ACE2 under force. We propose that blocking this site via neutralizing antibody or nanobody could prove an effective strategy to inhibit S-ACE2 interactions. url: https://doi.org/10.1101/2020.09.21.305490 doi: 10.1101/2020.09.21.305490 id: cord-312414-g5px0b65 author: Takagi, Akira title: An immunodominance hierarchy exists in CD8+ T cell responses to HLA-A*02:01-restricted epitopes identified from the non-structural polyprotein 1a of SARS-CoV-2 date: 2020-09-19 words: 4076.0 sentences: 230.0 pages: flesch: 61.0 cache: ./cache/cord-312414-g5px0b65.txt txt: ./txt/cord-312414-g5px0b65.txt summary: As shown in Fig. 2 , the intracellular cytokine staining (ICS) assay showed that 173 significant numbers of IFN--producing CD8+ T cells were elicited in mice immunized 174 with 18 liposomal peptides including pp1a-38, -52, -84, -103, -445, -597, -641, -1675, 175 -2785, -2884, -3083, -3403, -3467, -3583, -3662, -3710, -3732, and -3886, revealing that 176 these 18 peptides are HLA-A*02:01-restricted CTL epitopes derived from SARS-CoV-2 177 pp1a. However, any of 18 185 epitopes are not found in the amino acid sequence of either MERS-CoV or the four 186 common cold human coronaviruses involving HCoV-OC43, In the 18 positive peptides, 10 peptides including pp1a-38, -84, -641, -1675, -2884, 189 -3467, -3583, -3662, -3710, and -3732 were selected for the following analyses because 190 of the high ratios of IFN- + cells in CD8 + T cells (Fig. 2) . At first glance, the graphs of CD107a ( Taken together, 10 peptides differed significantly in their ability to induce 226 SARS-CoV-2 pp1a-specific CTLs when mice were immunized with the mixture of 10 227 peptides in liposomes. abstract: COVID-19 vaccines are being rapidly developed and human trials are underway. Almost all of these vaccines have been designed to induce antibodies targeting spike protein of SARS-CoV-2 in expectation of neutralizing activities. However, non-neutralizing antibodies are at risk of causing antibody-dependent enhancement. Further, the longevity of SARS-CoV-2-specific antibodies is very short. Therefore, in addition to antibody-induced vaccines, novel vaccines on the basis of SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs) should be considered in the vaccine development. Here, we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2. Eighty-two peptides were firstly predicted as epitope candidates on bioinformatics. Fifty-four in 82 peptides showed high or medium binding affinities to HLA-A*02:01. HLA-A*02:01 transgenic mice were then immunized with each of the 54 peptides encapsulated into liposomes. The intracellular cytokine staining assay revealed that 18 out of 54 peptides were CTL epitopes because of the induction of IFN-γ-producing CD8+ T cells. In the 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant CTL epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant over the other peptides. Surprisingly, all mice immunized with the liposomal 10 peptide mixture did not show the same reaction pattern to the 10 peptides. There were three pattern types that varied sequentially, suggesting the existence of an immunodominance hierarchy, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines. Importance For the development of vaccines based on SARS-CoV-2-specific cytotoxic T lymphocytes (CTLs), we attempted to identify HLA-A*02:01-restricted CTL epitopes derived from the non-structural polyprotein 1a of SARS-CoV-2. Out of 82 peptides predicted on bioinformatics, 54 peptides showed good binding affinities to HLA-A*02:01. Using HLA-A*02:01 transgenic mice, 18 in 54 peptides were found to be CTL epitopes in the intracellular cytokine staining assay. Out of 18 peptides, 10 peptides were chosen for the following analyses because of their high responses. To identify dominant epitopes, mice were immunized with liposomes containing the mixture of the 10 peptides. Some peptides were shown to be statistically predominant. Surprisingly, all immunized mice did not show the same reaction pattern to the 10 peptides. There were three pattern types that varied sequentially, suggesting the existence of an immunodominance hierarchy, which may provide us more variations in the epitope selection for designing CTL-based COVID-19 vaccines. url: https://doi.org/10.1101/2020.09.18.304493 doi: 10.1101/2020.09.18.304493 id: cord-103788-sxw4l9tt author: Talbot, Steven R. title: One score to rule them all: severity assessment in laboratory mice date: 2020-06-24 words: 5994.0 sentences: 345.0 pages: flesch: 56.0 cache: ./cache/cord-103788-sxw4l9tt.txt txt: ./txt/cord-103788-sxw4l9tt.txt summary: Body weight, the Mouse Grimace Scale score, burrowing behavior, and the telemetry-derived parameters heart rate, heart rate variability, temperature, and general activity were used to investigate the quality of indicating severity during postoperative recovery. In addition to the data for 184 building the RELSA reference set from TM-implanted mice, we evaluated RELSA performance as a 185 tool for severity comparisons between models by including data from three additional animal studies 186 (colitis, stress, sepsis). To exclude selection bias, we calculated the models'' severity level with a 285 full set of available variables: body weight change, burrowing behavior, MGS score and telemetry-286 derived parameters including hr, hrv and temperature. A RELSA score of 1 means that all contributing variables for a 584 test animal reached the same values as the largest observed deviations in the reference set with the 585 defined level of severity (here, "moderate"). abstract: Animal welfare and the refinement of experimental procedures are fundamental aspects of biomedical research. They provide the basis for robust experimental designs and reproducibility of results. In many countries, the determination of welfare is a mandatory legal requirement and implies the assessment of the degree of the severity that an animal experiences during an experiment. However, for an effective severity assessment, an objective and exact approach/system/strategy is needed. In light of these demands, we have developed the Relative Severity Assessment (RELSA) score. This comprehensive composite score was established on the basis of physiological and behavioral data from a surgical mouse study. Body weight, the Mouse Grimace Scale score, burrowing behavior, and the telemetry-derived parameters heart rate, heart rate variability, temperature, and general activity were used to investigate the quality of indicating severity during postoperative recovery. The RELSA scores not only revealed individual severity levels but also allowed a comparison of severity in distinct mouse models addressing colitis, sepsis, and restraint stress using a k-means clustering approach with the maximum achieved RELSA scores. We discriminated and classified data from sepsis nonsurvivors into the highest relative severity level. Data from mice after intraperitoneal transmitter implantation and sepsis survivor al were located in the next lower cluster, while data from mice subjected to colitis and restraint stress were placed in the lowest severity cluster. Analysis of individual variables and their combinations revealed model- and time-dependent contributions to severity levels. In conclusion, we propose the RELSA score as a validated tool for objective real-time applicability in severity assessment and as a first step towards a unified and accessible risk assessment tool in biomedical research. As an effective severity assessment system, it will fundamentally improve animal welfare, as well as data quality and reproducibility. url: https://doi.org/10.1101/2020.06.23.166801 doi: 10.1101/2020.06.23.166801 id: cord-104092-yau3r79c author: Tamming, Renee J. title: Atrx deletion in neurons leads to sexually-dimorphic dysregulation of miR-137 and spatial learning and memory deficits date: 2019-04-13 words: 4063.0 sentences: 206.0 pages: flesch: 47.0 cache: ./cache/cord-104092-yau3r79c.txt txt: ./txt/cord-104092-yau3r79c.txt summary: Mechanistically, we identify ATRX-dependent and sex-specific alterations in synaptic gene expression linked to Mir137 levels, a known regulator of presynaptic processes and spatial memory. Summary statement Ablation of the ATRX chromatin remodeler specifically in forebrain excitatory neurons of mice causes male-specific deficits in long-term spatial memory associated with miR-137 overexpression, transcriptional changes and structural alterations corresponding to preand post-synaptic abnormalities. A comprehensive analysis of these mice reveals that ATRX promotes long-term spatial learning and memory associated with morphological and synaptic ultrastructural changes in the hippocampus. We show that female mice lacking ATRX in neurons are protected from spatial learning and memory defects and identify sex-specific effects of ATRX loss on the expression of synaptic genes and miR-137. This study presents evidence that ATRX is required in a sex-specific manner in excitatory forebrain neurons for normal spatial learning and memory (Figure 8) [75] [76] [77] . abstract: Mutations in the ATRX chromatin remodeler are associated with syndromic and non-syndromic intellectual disability. Emerging evidence points to key roles for ATRX in preserving neuroprogenitor cell genomic stability, whereas ATRX function in differentiated neurons and memory processes are still unresolved. Here, we show that Atrx deletion in mouse forebrain glutamatergic neurons causes distinct hippocampal structural defects identified by magnetic resonance imaging. Ultrastructural analysis revealed fewer presynaptic vesicles and an enlarged postsynaptic area at CA1 apical dendrite-axon junctions. These synaptic defects are associated with impaired long-term contextual memory in male, but not female mice. Mechanistically, we identify ATRX-dependent and sex-specific alterations in synaptic gene expression linked to Mir137 levels, a known regulator of presynaptic processes and spatial memory. We conclude that ablation of Atrx in excitatory forebrain neurons leads to sexually dimorphic outcomes on miR-137 and on spatial memory, identifying a promising therapeutic target for neurological disorders caused by ATRX dysfunction. Summary statement Ablation of the ATRX chromatin remodeler specifically in forebrain excitatory neurons of mice causes male-specific deficits in long-term spatial memory associated with miR-137 overexpression, transcriptional changes and structural alterations corresponding to pre- and post-synaptic abnormalities. url: https://doi.org/10.1101/606442 doi: 10.1101/606442 id: cord-346335-el45v0a5 author: Tan, H.S. title: Fourier spectral density of the coronavirus genome date: 2020-08-11 words: 4646.0 sentences: 224.0 pages: flesch: 56.0 cache: ./cache/cord-346335-el45v0a5.txt txt: ./txt/cord-346335-el45v0a5.txt summary: We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density. An example of a seminal paper in this subject is that of Voss in [2] where the author found that the spectral density of the genome of many different species follows a power law of the form 1/k β in the low-frequency domain, with the exponent β potentially related to the organism''s evolutionary category. We develop a few models to characterize the typical spectrum, and in the process stumble upon a linear scaling law between a measure of the complexity of each genome and the power-law exponent that describes the enveloping curve of the low-frequency domain. abstract: We present an analysis of the coronavirus RNA genome via a study of its Fourier spectral density based on a binary representation of the nucleotide sequence. We find that at low frequencies, the power spectrum presents a small and distinct departure from the behavior expected from an uncorrelated sequence. We provide a couple of simple models to characterize such deviations. Away from a small low-frequency domain, the spectrum presents largely stochastic fluctuations about fixed values which vary inversely with the genome size generally. It exhibits no other peaks apart from those associated with triplet codon usage. We uncover an interesting, new scaling law for the coronavirus genome: the complexity of the genome scales linearly with the power-law exponent that characterizes the enveloping curve of the low-frequency domain of the spectral density. url: https://doi.org/10.1101/2020.06.30.180034 doi: 10.1101/2020.06.30.180034 id: cord-317123-0tdfvlqd author: Tan, Xiaotian title: Rapid and quantitative detection of COVID-19 markers in micro-liter sized samples date: 2020-04-21 words: 4154.0 sentences: 220.0 pages: flesch: 52.0 cache: ./cache/cord-317123-0tdfvlqd.txt txt: ./txt/cord-317123-0tdfvlqd.txt summary: Here, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen – S protein in serum. We also characterized various humanized monoclonal IgG, and identified a candidate with a high binding affinity towards SARS-CoV-2 S1 protein that can serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. In this work, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, and sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen -S protein, both of which are spiked in serum, as a model system. For the anti-S1 IgG detection experiments (see Figure S2 (B) for the detailed protocol), various concentrations of monoclonal antibodies were prepared by diluting the stock solutions with 50 times diluted human serum (the serum was diluted with 1× reagent diluent, which correlates to 1% BSA). abstract: COVID-19 pandemic has caused tens of thousands of deaths and is now a severe threat to global health. Clinical practice has demonstrated that the SARS-CoV-2 S1 specific antibodies and viral antigens can be used as diagnostic and prognostic markers of COVID-19. However, the popular point-of-care biomarker detection technologies, such as the lateral-flow test strips, provide only yes/no information and have very limited sensitivities. Thus, it has a high false negative rate and cannot be used for the quantitative evaluation of patient’s immune response. Conventional ELISA (enzyme-linked immunosorbent assay), on the other hand, can provide quantitative, accurate, and sensitive results, but it involves complicated and expensive instruments and long assay time. In addition, samples need to be sent to centralized labs, which significantly increases the turn-around time. Here, we present a microfluidic ELISA technology for rapid (15-20 minutes), quantitative, sensitive detection of SARS-CoV-2 biomarkers using SARS-CoV-2 specific IgG and viral antigen – S protein in serum. We also characterized various humanized monoclonal IgG, and identified a candidate with a high binding affinity towards SARS-CoV-2 S1 protein that can serve as the calibration standard of anti-SARS-CoV-2 S1 IgG in serological analyses. Furthermore, we demonstrated that our microfluidic ELISA platform can be used for rapid affinity evaluation of monoclonal anti-S1 antibodies. The microfluidic ELISA device is highly portable and requires less than 10 μL of samples for each channel. Therefore, our technology will greatly facilitate rapid and quantitative analysis of COVID-19 patients and vaccine recipients at point-of-care. url: https://doi.org/10.1101/2020.04.20.052233 doi: 10.1101/2020.04.20.052233 id: cord-353099-38bz0acw author: Tang, Mei San title: Association between SARS-CoV-2 neutralizing antibodies and commercial serological assays date: 2020-07-02 words: 1034.0 sentences: 70.0 pages: flesch: 51.0 cache: ./cache/cord-353099-38bz0acw.txt txt: ./txt/cord-353099-38bz0acw.txt summary: Methods 67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Results The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. Conclusion COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. The correlation of the SARS-CoV-2 neutralizing titer with the ratio reported by the 162 Roche, Abbott, and EI assays was 0.29, 0.47, and 0.46 respectively (Figure 2A-C) . Increased neutralizing antibody titers were also higher in patients that were intubated, 201 had cardiac injury, or AKI relative to those with milder COVID-19 symptoms ( Figure 202 4B-D). abstract: Introduction Commercially available SARS-CoV-2 serological assays based on different viral antigens have been approved for the qualitative determination of anti-SARS-CoV-2 antibodies. However, there is limited published data associating the results from commercial assays with neutralizing antibodies. Methods 67 specimens from 48 patients with PCR-confirmed COVID-19 and a positive result by the Roche Elecsys SARS-CoV-2, Abbott SARS-CoV-2 IgG, or EUROIMMUN SARS-CoV-2 IgG assays and 5 control specimens were analyzed for the presence of neutralizing antibodies to SARS-CoV-2. Correlation, concordance, positive percent agreement (PPA), and negative percent agreement (NPA) were calculated at several cutoffs. Results were compared in patients categorized by clinical outcomes. Results The correlation between SARS-CoV-2 neutralizing titer (EC50) and the Roche, Abbott, and EUROIMMUN assays was 0.29, 0.47, and 0.46 respectively. At an EC50 of 1:32, the concordance kappa with Roche was 0.49 (95% CI; 0.23-0.75), with Abbott was 0.52 (0.28-0.77), and with EUROIMMUN was 0.61 (0.4-0.82). At the same neutralizing titer, the PPA and NPA for the Roche was 100% (94-100) & 56% (30-80); Abbott was 96% (88-99) & 69% (44-86); and EUROIMMUN was 91% (80-96) & 81% (57-93) for distinguishing neutralizing antibodies. Patients who died, were intubated, or had a cardiac injury from COVID-19 infection had significantly higher neutralizing titers relative to those with mild symptoms. Conclusion COVID-19 patients generate an antibody response to multiple viral proteins such that the calibrator ratios on the Roche, Abbott, and EUROIMMUN assays are all associated with SARS-CoV-2 neutralization. Nevertheless, commercial serological assays have poor NPA for SARS-CoV-2 neutralization, making them imperfect proxies for neutralization. url: https://doi.org/10.1101/2020.07.01.182220 doi: 10.1101/2020.07.01.182220 id: cord-103350-jj9pc4a6 author: Tang, Pingtao title: An HIV-Tat inducible mouse model system of childhood HIV-associated nephropathy date: 2020-05-08 words: 4041.0 sentences: 204.0 pages: flesch: 46.0 cache: ./cache/cord-103350-jj9pc4a6.txt txt: ./txt/cord-103350-jj9pc4a6.txt summary: rAd-Tat and LacZ control vectors (2 × 109) were expressed in the kidney of newborn wild type and HIV-transgenic (Tg26) FVB/N mice without significant proteinuria (n = 5 8 per group). Results HIV-Tat induced the expression of HIV-1 genes (env) and heparin binding growth factors in the kidney of HIV-Tg26 mice, and precipitated HIVAN in the first month of life. Summary statement We developed a new inducible mouse model system of childhood HIV-associated nephropathy, and demonstrated that HIV-Tat plays a critical role in this renal disease acting in synergy with other HIV-1 genes and heparin binding cytokines. Therefore, we carried out this study to determine whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and define whether this approach could be used to generate an inducible mouse model system of childhood HIVAN. Our study showed that the activation and basic binding domains of Tat are sufficient to induce the renal expression of HIV-genes and precipitate HIVAN in young mice. abstract: Background Modern antiretroviral therapies (ART) have decreased the prevalence of HIV-associated nephropathy (HIVAN). Nonetheless, we continue to see children and adolescents with HIVAN all over the world. Furthermore, once HIVAN is established in children, it is difficult to revert its long-term progression, and we need better animal models of childhood HIVAN to test new treatments. Objectives To define whether the HIV-1 trans-activator (Tat) gene precipitates HIVAN in young mice, and to develop an inducible mouse model of childhood HIVAN. Design/Methods An HIV-Tat gene cloned from a child with HIVAN was used to generate recombinant adenoviral vectors (rAd-Tat). rAd-Tat and LacZ control vectors (2 × 109) were expressed in the kidney of newborn wild type and HIV-transgenic (Tg26) FVB/N mice without significant proteinuria (n = 5 - 8 per group). Mice were sacrificed 7 and 35 days later to assess their renal outcome, the expression of HIV-genes and growth factors, and markers of cell growth and differentiation by RT-qPCR, immunohistochemistry, and/or Western blots. Results HIV-Tat induced the expression of HIV-1 genes (env) and heparin binding growth factors in the kidney of HIV-Tg26 mice, and precipitated HIVAN in the first month of life. No significant renal changes were detected in wild type mice infected with rAd-Tat vectors, suggesting that HIV-Tat alone does not induce renal disease. Conclusion This new mouse model of childhood HIVAN highlights the critical role that HIV-Tat plays in the pathogenesis of HIVAN, and could be used to study the pathogenesis and treatment of HIVAN in children and adolescents. Summary statement We developed a new inducible mouse model system of childhood HIV-associated nephropathy, and demonstrated that HIV-Tat plays a critical role in this renal disease acting in synergy with other HIV-1 genes and heparin binding cytokines. url: https://doi.org/10.1101/2020.05.06.081851 doi: 10.1101/2020.05.06.081851 id: cord-104081-a3fx8tyd author: Tang, Tiffany title: Proteolytic activation of the SARS-CoV-2 spike S1/S2 site: a re-evaluation of furin cleavage date: 2020-10-05 words: 4004.0 sentences: 206.0 pages: flesch: 57.0 cache: ./cache/cord-104081-a3fx8tyd.txt txt: ./txt/cord-104081-a3fx8tyd.txt summary: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its spike (S) protein to mediate viral entry into host cells. Our results demonstrate that S1/S2 pre-cleavage is essential for plasma membrane entry into Calu-3 cells, a model lung epithelial cell line, but not for endosomal entry Vero E6 cells, a model cell culture line, and that other proteases in addition to furin are responsible for processing SARS-CoV-2 S1/S2. dec-RVKR-CMK treatment had no significant impact on SARS-CoV S mediated infection of Vero E6 and Calu-3 cells (Figure 6A and 6B) , suggesting that dec-RVKR-CMK impacts on SARS-CoV-2 S is due to inhibiting the S1/S2 pre-cleavage and not due to some general effect on protein expression. Different residues in the SARS-CoV spike protein determine cleavage and activation by the host cell protease TMPRSS2 Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses its spike (S) protein to mediate viral entry into host cells. Cleavage of the S protein at the S1/S2 and/or S2’ site is known to activate the S protein for viral entry, which can occur at either the cell plasma membrane or the endosomal membrane. Previous studies show that SARS-CoV-2 has a unique insert at the S1/S2 site that can be cleaved by furin, which expands viral tropism to lung cells. Here, we analyze the presence of a furin S1/S2 site in related CoVs and offer thoughts on the implications of SARS-CoV-2’s unique insert on its origin. We also utilized viral pseudoparticles to study the impact of the S1/S2 cleavage on infectivity. Our results demonstrate that S1/S2 pre-cleavage is essential for plasma membrane entry into Calu-3 cells, a model lung epithelial cell line, but not for endosomal entry Vero E6 cells, a model cell culture line, and that other proteases in addition to furin are responsible for processing SARS-CoV-2 S1/S2. url: https://doi.org/10.1101/2020.10.04.325522 doi: 10.1101/2020.10.04.325522 id: cord-286466-scokdxp2 author: Tani, Hideki title: Evaluation of SARS-CoV-2 neutralizing antibodies using a vesicular stomatitis virus possessing SARS-CoV-2 spike protein date: 2020-08-23 words: 2558.0 sentences: 155.0 pages: flesch: 54.0 cache: ./cache/cord-286466-scokdxp2.txt txt: ./txt/cord-286466-scokdxp2.txt summary: The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an immunofluorescence assay (IFA). The neutralization values of the serum 31 samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative 32 donors against the pseudotyped virus infection evaluated by the CRNT were compared with 33 was designated as pCAG-SARS-CoV-2. Vero cells were treated with serially diluted sera or whole blood of convalescent patients with 145 COVID-19 or PCR-negative donors and then inoculated with Sfullpv, St19pv, or VSVpv. To 146 remove hematopoietic cells from whole blood samples, centrifugation was performed at 2,000 × g 147 for 5 min. To determine the specificity of infection of Sfullpv and St19pv, a neutralization assay of the 183 pseudotyped viruses was performed using sera of two hospitalized COVID-19 patients. abstract: SARS-CoV-2 is a novel coronavirus that emerged in 2019 and is now classified in the genus Coronavirus with closely related SARS-CoV. SARS-CoV-2 is highly pathogenic in humans and is classified as a biosafety level (BSL)-3 pathogen, which makes manipulating it relatively difficult due to its infectious nature. To circumvent the need for BSL-3 laboratories, an alternative assay was developed that avoids live virus and instead uses a recombinant VSV expressing luciferase and possesses the full length or truncated spike proteins of SARS-CoV-2. Furthermore, to measure SARS-CoV-2 neutralizing antibodies under BSL2 conditions, a chemiluminescence reduction neutralization test (CRNT) for SARS-CoV-2 was developed. The neutralization values of the serum samples collected from hospitalized patients with COVID-19 or SARS-CoV-2 PCR-negative donors against the pseudotyped virus infection evaluated by the CRNT were compared with antibody titers determined from an immunofluorescence assay (IFA). The CRNT, which used whole blood collected from hospitalized patients with COVID-19, was also examined. As a result, the inhibition of pseudotyped virus infection was specifically observed in both serum and whole blood and was also correlated with the results of the IFA. In conclusion, the CRNT for COVID-19 is a convenient assay system that can be performed in a BSL-2 laboratory with high specificity and sensitivity for evaluating the occurrence of neutralizing antibodies against SARS-CoV-2. url: https://doi.org/10.1101/2020.08.21.262295 doi: 10.1101/2020.08.21.262295 id: cord-352073-rdhjj72g author: Taniwaki, S.A title: Resource optimization in COVID-19 diagnosis date: 2020-06-26 words: 1910.0 sentences: 98.0 pages: flesch: 57.0 cache: ./cache/cord-352073-rdhjj72g.txt txt: ./txt/cord-352073-rdhjj72g.txt summary: The emergence and rapid dissemination worldwide of a novel Coronavirus (SARS-CoV-2) results in decrease of swabs availability for clinical samples collection, as well as, reagents for RT-qPCR diagnostic kits considered a confirmatory test for COVID-19 infection. This manuscript reports on the optimization of the Charité and the CDC RT-qPCR protocols for SARS-CoV-2 detection regarding concentration and volumes of reagents for both probe and intercalant agent-based platforms, as well as on the substitution of rayon swabs for cotton swabs for sample collection. Performance of E and RdRp genes of SARS-CoV-2 RT-qPCRs, based on final reaction volume of 10 µL with 2 µL of RNA (Table 1) , were verified with a relative standard curve built with 10 -2 to 10 -8 dilutions of positive RNA control. Tabela 4 -Probe-based RT-qPCR to the E gene of serial dilutions of SARS-CoV-2 sampled with cotton and rayon swabs. abstract: The emergence and rapid dissemination worldwide of a novel Coronavirus (SARS-CoV-2) results in decrease of swabs availability for clinical samples collection, as well as, reagents for RT-qPCR diagnostic kits considered a confirmatory test for COVID-19 infection. This scenario, showed the requirement of improve de diagnostic capacity, so the aim of this study were to verify the possibility of reducing the reaction volume of RT-qPCR and to test cotton swabs as alternative for sample collection. RT-qPCR volumes and RNA sample concentration were optimized without affecting the sensitivity of assays, using both probe-based and intercalation dyes methods. Although rayon swabs showed better performance, cotton swabs could be used as alternative type for clinical sample collection. COVID-19 laboratory diagnosis is important to isolate and restrict the dissemination of virus, so seek for alternatives to decrease the coast of assays improve the control of disease. url: https://doi.org/10.1101/2020.06.25.172528 doi: 10.1101/2020.06.25.172528 id: cord-102376-wk70iipl author: Tausch, Simon H. title: PathoLive – Real-time pathogen identification from metagenomic Illumina datasets date: 2020-04-14 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Motivation Over the past years, NGS has become a crucial workhorse for open-view pathogen diagnostics. Yet, long turnaround times result from using massively parallel high-throughput technologies as the analysis can only be performed after sequencing has finished. The interpretation of results can further be challenged by contaminations, clinically irrelevant sequences, and the sheer amount and complexity of the data. Results We implemented PathoLive, a real-time diagnostics pipeline for the detection of pathogens from clinical samples hours before sequencing has finished. Based on real-time alignment with HiL-ive2, mappings are scored with respect to common contaminations, low-entropy areas, and sequences of widespread, non-pathogenic organisms. The results are visualized using an interactive taxonomic tree that provides an easily interpretable overview of the relevance of hits. For a human plasma sample that was spiked in vitro with six pathogenic viruses, all agents were clearly detected after only 40 of 200 sequencing cycles. For a real-world sample from Sudan the results correctly indicated the presence of Crimean-Congo hemorrhagic Fever Virus. In a second real-world dataset from the 2019 SARS-CoV-2 outbreak in Wuhan, we found the presence of a SARS Coronavirus as the most relevant hit without the novel virus reference genome being included in the database. For all samples, clinically irrelevant hits were correctly de-emphasized. Our approach is valuable to obtain fast and accurate NGS-based pathogen identifications and correctly prioritize and visualize them based on their clinical significance. Availability PathoLive is open source and available on GitLab (https://gitlab.com/rkibioinformatics/PathoLive) and BioConda (conda install –c bioconda patholive). Contact Bernhard.Renard@hpi.de, NitscheA@rki.de url: https://doi.org/10.1101/402370 doi: 10.1101/402370 id: cord-104122-klvx927g author: Tayfuroglu, Omer title: An Accurate Free Energy Method for Solvation of Organic Compounds and Binding to Proteins date: 2020-05-28 words: 2408.0 sentences: 160.0 pages: flesch: 46.0 cache: ./cache/cord-104122-klvx927g.txt txt: ./txt/cord-104122-klvx927g.txt summary: The method is adopted from ANI-1ccx neural network potentials (Machine Learning) for the Atomic Simulation Environment (ASE) and predicts the single point energies at the accuracy of CCSD(T)/CBS level for the entire configurational space that is sampled by Molecular Dynamics (MD) simulations. [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] More sophisticated methods to calculate the potential binding free energy of inhibitor candidate to the protein ranges from post molecular dynamics simulations such as Molecular 57 Recently several models using active learning such as ANI-1, 58 ANI-1x 59 and ANI-1cxx 60 Here, we introduce a new strategy to estimate free energies of solvation of small organic compounds and binding to proteins in explicit solvent using single end-state MD simulations. The method is adopted from ANI-1ccx neural network potentials (Machine Learning) for the The insertion of the ligand to an environment of solvent (solvation free energy) or receptor (binding free energy) can be defined by a coupling parameter, λ. abstract: Here, we introduce a new strategy to estimate free energies using single end-state molecular dynamics simulation trajectories. The method is adopted from ANI-1ccx neural network potentials (Machine Learning) for the Atomic Simulation Environment (ASE) and predicts the single point energies at the accuracy of CCSD(T)/CBS level for the entire configurational space that is sampled by Molecular Dynamics (MD) simulations. Our preliminary results show that the method can be as accurate as Bennet-Acceptance-Ration (BAR) with much reduced computational cost. Not only does it enable to calculate solvation free energies of small organic compounds, but it is also possible to predict absolute and relative binding free energies in ligand-protein complex systems. Rapid calculation also enables to screen small organic molecules from databases as potent inhibitors to any drug targets. url: https://doi.org/10.1101/2020.05.26.116459 doi: 10.1101/2020.05.26.116459 id: cord-103345-v555a2ll author: Taylor, Adrian title: The novel roles of choline transporter-like 1 and 2 in ethanolamine transport date: 2020-08-28 words: 3722.0 sentences: 210.0 pages: flesch: 53.0 cache: ./cache/cord-103345-v555a2ll.txt txt: ./txt/cord-103345-v555a2ll.txt summary: These data firmly established that CTL1 and CTL2 are the first identified ethanolamine transporters in the whole cells and mitochondria, with intrinsic roles in de novo PE synthesis by the CDP-Etn Kennedy pathway and compartmentation of intracellular ethanolamine. PC and PE are synthesized de novo by CDP-Cho and CDP-Etn branches of the Kennedy pathway in which the extracellular substrates choline (Cho) and ethanolamine (Etn) are actively transported into the cell, phosphorylated and coupled with diacylglycerols (DAG) to form the final phospholipid product. While multiple transport systems have been established for Cho, Etn transport is poorly characterized and there is no single gene/protein assigned a transport function for mammalian Etn. Cho transport for membrane phospholipid synthesis is mediated by Cho transporter like protein CTL1/SLC44A1 (3) . M1 and M2 cells only express CTL2 and at levels similar to Ctrl and Cos 7 cells, and do not have a functional CTL1 protein ( Fig. 2A,D) , strongly implicating CTL2 as responsible for the low affinity Etn transport. abstract: We examined a novel function of mammalian Choline-Transporter-Like proteins CTL1/SLC44A1 and CTL2/SLC44A2 in ethanolamine transport. We established two distinct ethanolamine transport systems of a high affinity (K1 = 55.6 - 66.5 μM), mediated by CTL1, and of a low affinity (K2 = 275 - 299 μM), mediated by CTL2. Both types of transport are Na+-independent and mediated in a pH dependent manner, as expected for ethanolamine/H+ antiporters. Primary human fibroblasts with separate frameshift mutations (M1= SLC44A1 ΔAsp517 and M2= SLC44A1 ΔSer126) are devoid of CTL1 ethanolamine transport but maintain unaffected CTL2 transport. The lack of CTL1 or CTL2 reduced the ethanolamine transport, the flux by the CDP-ethanolamine Kennedy pathway and PE synthesis. Overexpression of CTL1 in SLC44A1 ΔSer126 (M2) cells improved the ethanolamine transport and PE synthesis. The SLC44A1 ΔSer126 cells are reliant on CTL2 function and CTL2 siRNA almost completely abolished ethanolamine transport in the whole cells and mitochondria. Overexpression of CTL1 and CTL2 cDNAs increased ethanolamine transport in control and SLC44A1ΔSer126 cells. CTL1 and CTL2 facilitated mitochondrial ethanolamine uptake, but the transport mediated by CTL1 is predominant in the whole cells and mitochondria. These data firmly established that CTL1 and CTL2 are the first identified ethanolamine transporters in the whole cells and mitochondria, with intrinsic roles in de novo PE synthesis by the CDP-Etn Kennedy pathway and compartmentation of intracellular ethanolamine. Significance The lack of Choline Transporter Like 1 (SLC44A1/CTL1) is the primary cause of a new neurodegenerative disorder with elements of childhood-onset parkinsonism and mitochondrial dysfunction. SLC44A2/CTL2 encodes the human neutrophil antigen 3, causes autoimmune hearing loss and Meniere’s disease, and has been recently identified as the main risk factor for thrombosis-the major cause of death in Covid-19 patients. Our investigation provides insights into the novel functions of CTL1 and CTL2 as intrinsic ethanolamine transporters. CTL1 and CTL2 are high and low affinity transporters, with direct roles in the membrane phospholipid synthesis. The work contributes to new knowledge for CTL1 and CTL2 independent transport functions and the optimization of prevention and treatment strategies in those various diseases. url: https://doi.org/10.1101/2020.08.27.270223 doi: 10.1101/2020.08.27.270223 id: cord-102412-cnlvyey4 author: Tekman, Mehmet title: A single-cell RNA-seq Training and Analysis Suite using the Galaxy Framework date: 2020-08-28 words: 6419.0 sentences: 300.0 pages: flesch: 53.0 cache: ./cache/cord-102412-cnlvyey4.txt txt: ./txt/cord-102412-cnlvyey4.txt summary: Results Here we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The analysis of scRNA-seq within Galaxy was a two-pronged e ort concentrated on bringing high quality single-cell tools into Galaxy, and providing the necessary work ows and training to accompany them. The training pictographically guides users through the concepts of extracting cell barcodes from the protocol, explains the signi cance of UMIs in the process of read deduplication with illustrative examples, and instructs the user in the process of performing further quality controls on their data during the post-mapping process via RNA STAR and other tools that are native to Galaxy. A Galaxy-based training resource for single-cell RNA-sequencing quality control and analyses abstract: Background The vast ecosystem of single-cell RNA-seq tools has until recently been plagued by an excess of diverging analysis strategies, inconsistent file formats, and compatibility issues between different software suites. The uptake of 10x Genomics datasets has begun to calm this diversity, and the bioinformatics community leans once more towards the large computing requirements and the statistically-driven methods needed to process and understand these ever-growing datasets. Results Here we outline several Galaxy workflows and learning resources for scRNA-seq, with the aim of providing a comprehensive analysis environment paired with a thorough user learning experience that bridges the knowledge gap between the computational methods and the underlying cell biology. The Galaxy reproducible bioinformatics framework provides tools, workflows and trainings that not only enable users to perform one-click 10x preprocessing, but also empowers them to demultiplex raw sequencing from custom tagged and full-length sequencing protocols. The downstream analysis supports a wide range of high-quality interoperable suites separated into common stages of analysis: inspection, filtering, normalization, confounder removal and clustering. The teaching resources cover an assortment of different concepts from computer science to cell biology. Access to all resources is provided at the singlecell.usegalaxy.eu portal. Conclusions The reproducible and training-oriented Galaxy framework provides a sustainable HPC environment for users to run flexible analyses on both 10x and alternative platforms. The tutorials from the Galaxy Training Network along with the frequent training workshops hosted by the Galaxy Community provide a means for users to learn, publish and teach scRNA-seq analysis. Key Points Single-cell RNA-seq has stabilised towards 10x Genomics datasets. Galaxy provides rich and reproducible scRNA-seq workflows with a wide range of robust tools. The Galaxy Training Network provides tutorials for the processing of both 10x and non-10x datasets. url: https://doi.org/10.1101/2020.06.06.137570 doi: 10.1101/2020.06.06.137570 id: cord-315760-9g8901v6 author: Teng, Xufei title: Compositional Variability and Mutation Spectra of Monophyletic SARS-CoV-2 Clades date: 2020-08-30 words: 3532.0 sentences: 182.0 pages: flesch: 59.0 cache: ./cache/cord-315760-9g8901v6.txt txt: ./txt/cord-315760-9g8901v6.txt summary: Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code, to molecular mechanisms based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on replicase-transcriptase complex. Our analysis starts with primary sequence information and identity-based phylogeny based on 22,051 SARS-CoV-2 genome sequences and evaluation of sequence variation patterns as mutation spectrum and its 12 permutations among organized clades tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings include: (1) The most dominant mutation is C-to-U permutation whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity albeit assumed most slightly deleterious. We have further examined the compositional subtleties among the clades and clusters with 304 a focus on G+C and purine content variability as both contents appear drifting toward optima 305 in SARS-CoV-2 and its relatives ( Figure 5C and 5D). abstract: COVID-19 and its causative pathogen SARS-CoV-2 have rushed the world into a staggering pandemic in a few months and a global fight against both is still going on. Here, we describe an analysis procedure where genome composition and its variables are related, through the genetic code, to molecular mechanisms based on understanding of RNA replication and its feedback loop from mutation to viral proteome sequence fraternity including effective sites on replicase-transcriptase complex. Our analysis starts with primary sequence information and identity-based phylogeny based on 22,051 SARS-CoV-2 genome sequences and evaluation of sequence variation patterns as mutation spectrum and its 12 permutations among organized clades tailored to two key mechanisms: strand-biased and function-associated mutations. Our findings include: (1) The most dominant mutation is C-to-U permutation whose abundant second-codon-position counts alter amino acid composition toward higher molecular weight and lower hydrophobicity albeit assumed most slightly deleterious. (2) The second abundance group includes: three negative-strand mutations U-to-C, A-to-G, G-to-A and a positive-strand mutation G-to-U generated through an identical mechanism as C-to-U. (3) A clade-associated and biased mutation trend is found attributable to elevated level of the negative-sense strand synthesis. (4) Within-clade permutation variation is very informative for associating non-synonymous mutations and viral proteome changes. These findings demand a bioinformatics platform where emerging mutations are mapped on to mostly subtle but fast-adjusting viral proteomes and transcriptomes to provide biological and clinical information after logical convergence for effective pharmaceutical and diagnostic applications. Such thoughts and actions are in desperate need, especially in the middle of the War against COVID-19. url: https://doi.org/10.1101/2020.08.26.267781 doi: 10.1101/2020.08.26.267781 id: cord-328695-nptfd6c2 author: Tengs, Torstein title: A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species date: 2020-06-29 words: 1969.0 sentences: 102.0 pages: flesch: 51.0 cache: ./cache/cord-328695-nptfd6c2.txt txt: ./txt/cord-328695-nptfd6c2.txt summary: title: A mobile genetic element in the SARS-CoV-2 genome is shared with multiple insect species We document here the presence of s2m, a highly conserved, mobile genetic element with unknown function, in both the SARS-CoV-2 genome and a large number of insect genomes. Although s2m is not universally present among coronaviruses and appears to undergo horizontal transfer, the high sequence conservation and universal presence of s2m among isolates of SARS-CoV-2 indicate that, when present, the element is essential for viral function. The presence of s2m in the SARS-CoV-2 genome (GenBank accession MN908947, position 29727-29768) and other members of this group is probably the result of a single horizontal transfer event, predating the divergence of the SARS-related viruses (Tengs, et al. The insect species that contain s2m (and the associated protein) are distantly related, indicating either a deep evolutionary origin with multiple losses or that this genetic construct is also a mobile element, perhaps using viruses as a vector . abstract: Unprecedented quantities of sequence data have been generated from the newly emergent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causative agent of COVID-19. We document here the presence of s2m, a highly conserved, mobile genetic element with unknown function, in both the SARS-CoV-2 genome and a large number of insect genomes. Although s2m is not universally present among coronaviruses and appears to undergo horizontal transfer, the high sequence conservation and universal presence of s2m among isolates of SARS-CoV-2 indicate that, when present, the element is essential for viral function. url: https://doi.org/10.1101/2020.06.29.177030 doi: 10.1101/2020.06.29.177030 id: cord-336938-03366q9t author: Thacker, Vivek V title: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model date: 2020-08-10 words: 2818.0 sentences: 169.0 pages: flesch: 49.0 cache: ./cache/cord-336938-03366q9t.txt txt: ./txt/cord-336938-03366q9t.txt summary: title: Rapid endothelialitis and vascular inflammation characterise SARS-CoV-2 infection in a human lung-on-chip model A combination of qRT-PCR, RNAscope, immunofluorescence, and ELISA measurements are used to study the dynamics of viral replication and host responses to a low dose infection of SARS-CoV-2 delivered to the apical surface of the epithelial face maintained at an air-liquid interface. We therefore establish a human lung-on-chip model for SARS-CoV-2 infections, and probe the viral growth kinetics, cellular localization and responses to a low dose infection using qRT-PCR, ELISA, RNAscope, immunofluorescence and confocal imaging (Fig. 1J) . Nevertheless, total RNA extracted from the apical and vascular channels of an infected LoC without macrophages at 1 dpi revealed >10 4 genomes in both epithelial and endothelial cells (Fig. 2C ) and genome copy numbers exceeded those for cellular housekeeping gene RNAseP (Fig. 2D ). Human iPSC-derived alveolar and airway epithelial cells can be cultured at air-liquid interface and express SARS-CoV-2 host factors abstract: Background Severe manifestations of COVID-19 include hypercoagulopathies and systemic endothelialitis. The underlying dynamics of damage to the vasculature, and whether it is a direct consequence of endothelial infection or an indirect consequence of immune cell mediated cytokine storms is unknown. This is in part because in vitro infection models are typically monocultures of epithelial cells or fail to recapitulate vascular physiology. Methods We establish a vascularised lung-on-chip infection model consisting of a co-culture of primary human alveolar epithelial cells (‘epithelial’) and human lung microvascular endothelial cells (‘endothelial’), with the optional addition of CD14+ macrophages to the epithelial side. A combination of qRT-PCR, RNAscope, immunofluorescence, and ELISA measurements are used to study the dynamics of viral replication and host responses to a low dose infection of SARS-CoV-2 delivered to the apical surface of the epithelial face maintained at an air-liquid interface. Findings SARS-CoV-2 inoculation does not lead to a productive amplification of infectious virions. However, both genomic and antisense viral RNA can be found in endothelial cells within 1-day post infection (dpi) and persist upto 3 dpi. This generates an NF-KB inflammatory response typified by IL-6 secretion and a weak antiviral interferon response even in the absence of immune cells. Endothelial inflammation leads to a progressive loss of barrier integrity, a subset of cells also shows a transient hyperplasic phenotype. Administration of Tocilizumab slows the loss of barrier integrity but does not reduce the occurrence of the latter. Interpretation Endothelial infection can occur through basolateral transmission from infected epithelial cells at the air-liquid interface. SARS-CoV-2 mediated inflammation occurs despite the lack of rapid viral replication and the consequences are cell-type dependent. Infected endothelial cells might be a key source of circulating IL-6 in COVID-19 patients. Vascular damage occurs independently of immune-cell mediated cytokine storms, whose effect would only exacerbate the damage. Finding Core support from EPEL. url: https://doi.org/10.1101/2020.08.10.243220 doi: 10.1101/2020.08.10.243220 id: cord-321166-nvphu1fm author: Thomson, Emma C. title: The circulating SARS-CoV-2 spike variant N439K maintains fitness while evading antibody-mediated immunity date: 2020-11-05 words: 9813.0 sentences: 514.0 pages: flesch: 55.0 cache: ./cache/cord-321166-nvphu1fm.txt txt: ./txt/cord-321166-nvphu1fm.txt summary: We find that the N439K mutation is associated with a similar clinical spectrum of disease and slightly higher viral loads in vivo compared with isolates with the wild-type N439 residue, and that it results in immune escape from polyclonal sera from a proportion of recovered individuals and a panel of neutralizing mAbs. N439K provides a sentinel example of immune escape, indicating that RBM variants must be evaluated when considering vaccines and the therapeutic or prophylactic use of mAbs. Long term control of the pandemic will require systematic monitoring of immune escape variants and selection of strategies that address the variants circulating in targeted populations. Fitness of this variant, N439K, was demonstrated by repeated emergence by convergent evolution, spread to multiple countries and significant representation in the SARS-CoV-2 sequence databases, the fact that the N439K RBD retains a high affinity interaction with the hACE2 receptor, efficient viral replication in cultured cells, and no disease attenuation in a large cohort of infected individuals. abstract: SARS-CoV-2 can mutate to evade immunity, with consequences for the efficacy of emerging vaccines and antibody therapeutics. Herein we demonstrate that the immunodominant SARS-CoV-2 spike (S) receptor binding motif (RBM) is the most divergent region of S, and provide epidemiological, clinical, and molecular characterization of a prevalent RBM variant, N439K. We demonstrate that N439K S protein has enhanced binding affinity to the hACE2 receptor, and that N439K virus has similar clinical outcomes and in vitro replication fitness as compared to wild- type. We observed that the N439K mutation resulted in immune escape from a panel of neutralizing monoclonal antibodies, including one in clinical trials, as well as from polyclonal sera from a sizeable fraction of persons recovered from infection. Immune evasion mutations that maintain virulence and fitness such as N439K can emerge within SARS-CoV-2 S, highlighting the need for ongoing molecular surveillance to guide development and usage of vaccines and therapeutics. url: https://doi.org/10.1101/2020.11.04.355842 doi: 10.1101/2020.11.04.355842 id: cord-300272-95o8yd7h author: Thépaut, Michel title: DC/L-SIGN recognition of spike glycoprotein promotes SARS-CoV-2 trans-infection and can be inhibited by a glycomimetic antagonist date: 2020-08-10 words: 6862.0 sentences: 356.0 pages: flesch: 53.0 cache: ./cache/cord-300272-95o8yd7h.txt txt: ./txt/cord-300272-95o8yd7h.txt summary: In the context of the current COVID-19 pandemic, attention is now focused on the SARS-CoV-2 virus Zhou et al., 2020) .Coronaviruses use a homotrimeric glycosylated spike (S) protein protruding from their viral envelope to interact with cell membranes and promote fusion upon proteolytic activation. Additionally, in the case of SARS-CoV-2, a new paradigm is needed to untangle the complex clinical picture, resulting in a vast range of possible symptoms and in a spectrum of disease severity associated on one hand with active viral replication and cell infection through interaction with ACE2 along the respiratory tract, and, on the other hand, to the development of excessive immune activation, i.e. the so called "cytokine storm", that is related to additional tissue damage and potential fatal outcomes. These observations prompted us to investigate the potential interaction of C-type lectins receptors, notably DC/L-SIGN with SARS-CoV-2, through glycan recognition of the spike envelope glycoprotein, as well at their potential role in SARS-CoV-2 transmission. abstract: The efficient spread of SARS-CoV-2 resulted in a pandemic that is unique in modern history. Despite early identification of ACE2 as the receptor for viral spike protein, much remains to be understood about the molecular events behind viral dissemination. We evaluated the contribution of C-type lectin receptors (CLRS) of antigen-presenting cells, widely present in air mucosa and lung tissue. DC-SIGN, L-SIGN, Langerin and MGL bind to diverse glycans of the spike using multiple interaction areas. Using pseudovirus and cells derived from monocytes or T-lymphocytes, we demonstrate that while virus capture by the CLRs examined does not allow direct cell infection, DC/L-SIGN, among these receptors, promote virus transfer to permissive ACE2+ cells. A glycomimetic compound designed against DC-SIGN, enable inhibition of this process. Thus, we described a mechanism potentiating viral capture and spreading of infection. Early involvement of APCs opens new avenues for understanding and treating the imbalanced innate immune response observed in COVID-19 pathogenesis url: https://doi.org/10.1101/2020.08.09.242917 doi: 10.1101/2020.08.09.242917 id: cord-297826-2nruf2g7 author: Tian, Jing-Hui title: SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice date: 2020-06-30 words: 2660.0 sentences: 171.0 pages: flesch: 60.0 cache: ./cache/cord-297826-2nruf2g7.txt txt: ./txt/cord-297826-2nruf2g7.txt summary: In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). Mice 171 immunized with 10 μg dose of NVX-CoV2373/Matrix-M induced antibodies that blocked 172 hACE2 receptor binding to S-protein and virus neutralizing antibodies 21-28-days after 173 a single priming dose ( Fig. 4B and 4C ). Importantly, we found the frequency 254 of IFN-γ + , TNF-α + , and IL-2 + cytokine-secreting CD4 + and CD8 + T cells was 255 significantly higher (p <0.0001) in spleens from the NVX-CoV2373/Matrix-M immunized 256 mice compared to mice immunized without adjuvant ( Fig. 6B and 6C) . Anti-S protein IgG titers were detected within 21-days of a single priming immunization 288 in animals immunized with NVX-CoV2373/Matrix-M across all the dose levels (GMT = 289 1,249-19,000). abstract: The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988). url: https://doi.org/10.1101/2020.06.29.178509 doi: 10.1101/2020.06.29.178509 id: cord-255440-ls1l2mlg author: Tindle, Courtney title: Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19 date: 2020-10-18 words: 9951.0 sentences: 525.0 pages: flesch: 53.0 cache: ./cache/cord-255440-ls1l2mlg.txt txt: ./txt/cord-255440-ls1l2mlg.txt summary: Besides the approaches described so far, there are a few more approaches used for modeling COVID-19-(i) 3D organoids from bronchospheres and tracheospheres have been established before (Hild and Jaffe, 2016; Rock et al., 2009; Tadokoro et al., 2016) and are now used in apical-out cultures for infection with SARS-COV-2 (Suzuki et al., 2020); (ii) the most common model used for drug screening is the air-liquid interphase (ALI model) in which pseudo-stratified primary bronchial or small airway epithelial cells are used to recreate the multilayered mucociliary epithelium (Mou et al., 2016; Randell et al., 2011) ; (iii) several groups have also generated 3D airway models from iPSCs or tissue-resident stem cells (Dye et al., 2015; Ghaedi et al., 2013; Konishi et al., 2016; McCauley et al., 2017; Miller et al., 2019; Wong et al., 2012) ; (iv) others have generated AT2 cells from iPSCs using closely overlapping protocols of sequential differentiation starting with definitive endoderm, anterior foregut endoderm, and distal alveolar expression (Chen et al., 2017; Gotoh et al., 2014; Huang et al., 2014; Jacob et al., 2017; Jacob et al., 2019; Yamamoto et al., 2017) . abstract: SARS-CoV-2, the virus responsible for COVID-19, causes widespread damage in the lungs in the setting of an overzealous immune response whose origin remains unclear. We present a scalable, propagable, personalized, cost-effective adult stem cell-derived human lung organoid model that is complete with both proximal and distal airway epithelia. Monolayers derived from adult lung organoids (ALOs), primary airway cells, or hiPSC-derived alveolar type-II (AT2) pneumocytes were infected with SARS-CoV-2 to create in vitro lung models of COVID-19. Infected ALO-monolayers best recapitulated the transcriptomic signatures in diverse cohorts of COVID-19 patient-derived respiratory samples. The airway (proximal) cells were critical for sustained viral infection, whereas distal alveolar differentiation (AT2→AT1) was critical for mounting the overzealous host immune response in fatal disease; ALO monolayers with well-mixed proximodistal airway components recapitulated both. Findings validate a human lung model of COVID-19, which can be immediately utilized to investigate COVID-19 pathogenesis and vet new therapies and vaccines. GRAPHIC ABSTRACT HIGHLIGHTS Human lung organoids with mixed proximodistal epithelia are created Proximal airway cells are critical for viral infectivity Distal alveolar cells are important for emulating host response Both are required for the overzealous response in severe COVID-19 IN BRIEF An integrated stem cell-based disease modeling and computational approach demonstrate how both proximal airway epithelium is critical for SARS-CoV-2 infectivity, but distal differentiation of alveolar pneumocytes is critical for simulating the overzealous host response in fatal COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33106807/ doi: 10.1101/2020.10.17.344002 id: cord-102199-mc6zruyx author: Toksvang, Linea Natalie title: Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review date: 2019-01-30 words: 2340.0 sentences: 144.0 pages: flesch: 40.0 cache: ./cache/cord-102199-mc6zruyx.txt txt: ./txt/cord-102199-mc6zruyx.txt summary: title: Hepatotoxicity during 6-thioguanine treatment in inflammatory bowel disease and childhood acute lymphoblastic leukaemia: a systematic review Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9–25% of the ALL patients in two of the four included RCTs using 6TG doses of 40–60 mg/m2/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. Oral 6-mercaptopurine versus oral 6-thioguanine and veno-occlusive disease in children with standard-risk acute lymphoblastic leukemia: report of the Children''s Oncology Group CCG-1952 clinical trial 6-Thioguanine associated nodular regenerative hyperplasia in patients with inflammatory bowel disease may induce portal hypertension Splitting a therapeutic dose of thioguanine may avoid liver toxicity and be an efficacious treatment for severe inflammatory bowel disease: a 2-center observational cohort study Early nodular hyperplasia of the liver occurring with inflammatory bowel diseases in association with thioguanine therapy abstract: Background The recently established association between higher levels of DNA-incorporated thioguanine nucleotides and lower relapse risk in childhood acute lymphoblastic leukaemia (ALL) calls for reassessment of prolonged 6-thioguanine (6TG) treatment, while avoiding the risk of hepatotoxicity. Objectives To assess the incidence of hepatotoxicity in patients treated with 6TG, and to explore if a safe dose of continuous 6TG can be established. Data sources Databases, conference proceedings, and reference lists of included studies were systematically searched for 6TG and synonyms from 1998–2018. Methods We included studies of patients with ALL or inflammatory bowel disorder (IBD) treated with 6TG, excluding studies with 6TG as part of an intensive chemotherapy regimen. We uploaded a protocol to PROSPERO (registration number CRD42018089424). Database and manual searches yielded 1823 unique records. Of these, 395 full-texts were screened for eligibility. Finally, 134 reports representing 42 studies were included. Results and conclusions We included data from 42 studies of ALL and IBD patients; four randomised controlled trials (RCTs) including 3,993 patients, 20 observational studies including 796 patients, and 18 case reports including 60 patients. Hepatotoxicity in the form of sinusoidal obstruction syndrome (SOS) occurred in 9–25% of the ALL patients in two of the four included RCTs using 6TG doses of 40–60 mg/m2/day, and long-term hepatotoxicity in the form of nodular regenerative hyperplasia (NRH) was reported in 2.5%. In IBD patients treated with 6TG doses of approximately 23 mg/m2/day, NRH occurred in 14% of patients; SOS has not been reported. At a 6TG dose of approximately 12 mg/m2/day, NRH was reported in 6% of IBD patients, which is similar to the background incidence. According to this review, doses at or below 12 mg/m2/day are rarely associated with notable hepatotoxicity and can probably be considered safe. url: https://doi.org/10.1101/535518 doi: 10.1101/535518 id: cord-102749-tgka0pl0 author: Tovo, Anna title: Taxonomic classification method for metagenomics based on core protein families with Core-Kaiju date: 2020-05-01 words: 7844.0 sentences: 352.0 pages: flesch: 47.0 cache: ./cache/cord-102749-tgka0pl0.txt txt: ./txt/cord-102749-tgka0pl0.txt summary: In this study, we first apply and compare different bioinformatics methods based on 16S ribosomal RNA gene and whole genome shotgun sequencing for taxonomic classification to three small mock communities of bacteria, of which the compositions are known. In particular, we propose an updated version of Kaiju, which combines the power of shotgun metagenomics data with a more focused marker gene classification method, similar to 16S rRNA, but based on core protein domain families (40, 41, 42, 43) from the PFAM database (44) . As shown in (27) , where different amplicon sequencing methods are tested on both simulated and real data and the results are compared to those obtained with metagenomic pipelines, the whole genome approach resulted to outperform the previous ones in terms of both number of identified strains, taxonomic and functional resolution and reliability on estimates of microbial relative abundance distribution in samples. abstract: Characterizing species diversity and composition of bacteria hosted by biota is revolutionizing our understanding of the role of symbiotic interactions in ecosystems. However, determining microbiomes diversity implies the classification of taxa composition within the sampled community, which is often done via the assignment of individual reads to taxa by comparison to reference databases. Although computational methods aimed at identifying the microbe(s) taxa are available, it is well known that inferences using different methods can vary widely depending on various biases. In this study, we first apply and compare different bioinformatics methods based on 16S ribosomal RNA gene and whole genome shotgun sequencing for taxonomic classification to three small mock communities of bacteria, of which the compositions are known. We show that none of these methods can infer both the true number of taxa and their abundances. We thus propose a novel approach, named Core-Kaiju, which combines the power of shotgun metagenomics data with a more focused marker gene classification method similar to 16S, but based on emergent statistics of core protein domain families. We thus test the proposed method on the three small mock communities and also on medium- and highly complex mock community datasets taken from the Critical Assessment of Metagenome Interpretation challenge. We show that Core-Kaiju reliably predicts both number of taxa and abundance of the analysed mock bacterial communities. Finally we apply our method on human gut samples, showing how Core-Kaiju may give more accurate ecological characterization and fresh view on real microbiomes. url: https://doi.org/10.1101/2020.01.08.898395 doi: 10.1101/2020.01.08.898395 id: cord-345405-ngpsgn63 author: Tremiliosi, Guilherme C. title: Ag nanoparticles-based antimicrobial polycotton fabrics to prevent the transmission and spread of SARS-CoV-2 date: 2020-06-26 words: 6259.0 sentences: 339.0 pages: flesch: 46.0 cache: ./cache/cord-345405-ngpsgn63.txt txt: ./txt/cord-345405-ngpsgn63.txt summary: An adaptation of ISO 18184 Determination of antiviral activity of textile products Standard Method [23] was used as a reference for a quantitative method to evaluate the treated polycotton''s ability to inactivate the SARS-CoV-2 virus particles (SARS-CoV-2/human/BRA/SP02cc/2020 -MT350282), under the tested conditions, at two different time intervals (2 and 5 minutes of contact time). The antiviral activity test was designed to determine the inactivation of viral particles upon short exposure to the products, which in this case were the Ag-based treated polycotton samples incubated in liquid media. Table 6 shows the number of copies of the control media without any fabric sample, non-treated polycotton, and the two Ag-based treated polycotton samples at the two different tested time periods. Application of silver nanoparticles to cotton fabric as an antibacterial textile finish Fibers Polym Antibacterial properties of cotton fabric treated with silver nanoparticles abstract: Pathogens (bacteria, fungus and virus) are becoming a potential threat to the health of human beings and environment worldwide. They widely exist in the environment, with characteristics of variety, spreading quickly and easily causing adverse reactions. In this work, an Ag-based material is used to be incorporated and functionalized in polycotton fabrics using pad-dry-cure method. This composite proved to be effective for inhibiting the SARS-CoV-2 virus, decreasing the number of replicates in 99.99% after an incubation period of 2 minutes. In addition, it caused 99.99% inhibition of the pathogens S. aureus, E. coli and C. albicans, preventing cross-infections and does not cause allergies or photoirritation processes, demonstrating the safety of its use. url: https://doi.org/10.1101/2020.06.26.152520 doi: 10.1101/2020.06.26.152520 id: cord-293640-pgrrurrc author: Tripathi, Satyendra C title: Renal carcinoma is associated with increased risk of coronavirus infections date: 2020-07-06 words: 3724.0 sentences: 202.0 pages: flesch: 48.0 cache: ./cache/cord-293640-pgrrurrc.txt txt: ./txt/cord-293640-pgrrurrc.txt summary: We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. TCGA data analysis also showed increased expression of all receptors except TMPRSS2 in renal tumor tissues as compared to their adjacent normal (Sup Fig 1) . Further, we specifically analyzed ACE2, which is a primary SARS-CoV receptor and DPP4, highly correlated to ACE2 across the kidney cancer subtypes along with immune cell signatures (innate and adaptive immunity, inflammatory cytokines and chemokines). ACE2, DPP4, ANPEP, and ENPEP each associated with a high level of immune infiltration, inflammatory chemokines, cytokines and markers of an immunosuppressive microenvironment and T cell exhaustion in KIRC tumors. The Tumor Immune System Interaction database (TISIDB) (http://cis.hku.hk/TISIDB/) platform was used to analyze the correlation of ACE2 with other CoV receptors (DPP4, ANPEP, ENPEP, TMPRSS2) expression in different renal carcinoma subtypes. abstract: The current pandemic COVID-19 has affected most severely to the people with old age, or with comorbidities such as hypertension, diabetes mellitus, chronic kidney disease, COPD, and cancers. Cancer patients are twice more likely to contract the disease because of the malignancy or treatment-related immunosuppression; hence identification of the vulnerable population among these patients is essential. It is speculated that along with ACE2, other auxiliary proteins (DPP4, ANPEP, ENPEP, TMPRSS2) might facilitate the entry of coronaviruses in the host cells. We took a bioinformatics approach to analyze the gene and protein expression data of these coronavirus receptors in human normal and cancer tissues of multiple organs. Here, we demonstrated an extensive RNA and protein expression profiling analysis of these receptors across solid tumors and normal tissues. We found that among all, renal tumor and normal tissues exhibited increased levels of ACE2, DPP4, ANPEP, and ENPEP. Our results revealed that TMPRSS2 may not be the co-receptor for coronavirus in renal carcinoma patients. The receptors’ expression levels were variable in different tumor stage, molecular and immune subtypes of renal carcinoma. In clear cell renal cell carcinomas, coronavirus receptors were associated with high immune infiltration, markers of immunosuppression, and T cell exhaustion. Our study indicates that CoV receptors may play an important role in modulating the immune infiltrate and hence cellular immunity in renal carcinoma. As our current knowledge of pathogenic mechanisms will improve, it may help us in designing focused therapeutic approaches. url: https://doi.org/10.1101/2020.07.02.184663 doi: 10.1101/2020.07.02.184663 id: cord-102734-ltuqoa2b author: Tsai, Hsiang-Yu title: Antagonistic Effects of Intraspecific Cooperation and Interspecific Competition on Thermal Performance date: 2020-05-04 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Understanding how climate-mediated biotic interactions shape thermal niche width is critical in an era of global change. Yet, most previous work on thermal niches has ignored detailed mechanistic information about the relationship between temperature and organismal performance, which can be described by a thermal performance curve. Here, we develop a model that predicts the width of thermal performance curves will be narrower in the presence of interspecific competitors, causing a species’ optimal breeding temperature to diverge from that of a competitor. We test this prediction in the Asian burying beetle Nicrophorus nepalensis, confirming that the divergence in actual and optimal breeding temperatures is the result of competition with blowflies. However, we further show that intraspecific cooperation enables beetles to outcompete blowflies by recovering their optimal breeding temperature. Ultimately, linking direct (abiotic factors) and indirect effects (biotic interactions) on niche width will be critical for understanding species-specific responses to climate change. url: https://doi.org/10.1101/2020.05.03.075325 doi: 10.1101/2020.05.03.075325 id: cord-323685-gjocoa60 author: Tsai, Shang-Jui title: Exosome-Mediated mRNA Delivery For SARS-CoV-2 Vaccination date: 2020-11-06 words: 5332.0 sentences: 289.0 pages: flesch: 49.0 cache: ./cache/cord-323685-gjocoa60.txt txt: ./txt/cord-323685-gjocoa60.txt summary: The resulting combinatorial vaccine, LSNME/SW1, was injected into thirteen weeks-old, male C57BL/6J mice, followed by interrogation of humoral and cellular immune responses to the SARS-CoV-2 nucleocapsid and spike proteins, as well as hematological and histological analysis to interrogate animals for possible adverse effects. Conclusion Taken together, these results validate the use of exosomes for delivering functional mRNAs into target cells in vitro and in vivo, and more specifically, establish that the LSNME/SW1 vaccine induced broad immunity to multiple SARS-CoV-2 proteins. These antigen-responsive CD4+ and CD8+ populations were present nearly two months after the final boost injection, indicating that LSNME/S W1 vaccination had elicited a sustained cellular immune response to both of these SARS-CoV-2 structural proteins. As for the future development of the LSNME/S W1 vaccine, we anticipate that follow-on studies in larger animal models at doses comparable to other mRNA vaccines will demonstrate a desirable combination of safety, balanced immune responses, and when challenged, protection against SARS-CoV-2 infection and/or disease. abstract: Background In less than a year from its zoonotic entry into the human population, SARS-CoV-2 has infected more than 45 million people, caused 1.2 million deaths, and induced widespread societal disruption. Leading SARS-CoV-2 vaccine candidates immunize with the viral spike protein delivered on viral vectors, encoded by injected mRNAs, or as purified protein. Here we describe a different approach to SARS-CoV-2 vaccine development that uses exosomes to deliver mRNAs that encode antigens from multiple SARS-CoV-2 structural proteins. Approach Exosomes were purified and loaded with mRNAs designed to express (i) an artificial fusion protein, LSNME, that contains portions of the viral spike, nucleocapsid, membrane, and envelope proteins, and (ii) a functional form of spike. The resulting combinatorial vaccine, LSNME/SW1, was injected into thirteen weeks-old, male C57BL/6J mice, followed by interrogation of humoral and cellular immune responses to the SARS-CoV-2 nucleocapsid and spike proteins, as well as hematological and histological analysis to interrogate animals for possible adverse effects. Results Immunized mice developed CD4+, and CD8+ T-cell reactivities that respond to both the SARS-CoV-2 nucelocapsid protein and the SARS-CoV-2 spike protein. These responses were apparent nearly two months after the conclusion of vaccination, as expected for a durable response to vaccination. In addition, the spike-reactive CD4+ T-cells response was associated with elevated expression of interferon gamma, indicative of a Th1 response, and a lesser induction of interleukin 4, a Th2-associated cytokine. Vaccinated mice showed no sign of altered growth, injection-site hypersensitivity, change in white blood cell profiles, or alterations in organ morphology. Consistent with these results, we also detected moderate but sustained anti-nucleocapsid and anti-spike antibodies in the plasma of vaccinated animals. Conclusion Taken together, these results validate the use of exosomes for delivering functional mRNAs into target cells in vitro and in vivo, and more specifically, establish that the LSNME/SW1 vaccine induced broad immunity to multiple SARS-CoV-2 proteins. url: https://doi.org/10.1101/2020.11.06.371419 doi: 10.1101/2020.11.06.371419 id: cord-351559-az4pgi9k author: Turjya, Rafeed Rahman title: Perversely expressed long noncoding RNAs can alter host response and viral proliferation in SARS-CoV-2 infection date: 2020-06-29 words: 2438.0 sentences: 173.0 pages: flesch: 48.0 cache: ./cache/cord-351559-az4pgi9k.txt txt: ./txt/cord-351559-az4pgi9k.txt summary: Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genes ADAR, EDN1, KYNU, MALL, TLR2 and YWHAG; and also AKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10 and PRKAR2A, host genes that interact with SARS-CoV-2 proteins. Conclusions Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option. abstract: Background Since December 2019, the world is experiencing an unprecedented crisis due to a novel coronavirus, SARS-CoV-2. Owing to poor understanding of pathogenicity, the virus is eluding treatment and complicating recovery. Regulatory roles of long non-coding RNAs (lncRNAs) during viral infection and associated antagonism of host antiviral immune responses has become more evident in last decade. To elucidate possible functions of lncRNAs in the COVID-19 pathobiology, we have utilized RNA-seq dataset of SARS-CoV-2 infected lung epithelial cells. Results Our analyses uncover 21 differentially expressed lncRNAs whose functions are broadly involved in cell survival and regulation of gene expression. By network enrichment analysis we find that these lncRNAs can directly interact with differentially expressed protein-coding genes ADAR, EDN1, KYNU, MALL, TLR2 and YWHAG; and also AKAP8L, EXOSC5, GDF15, HECTD1, LARP4B, LARP7, MIPOL1, UPF1, MOV10 and PRKAR2A, host genes that interact with SARS-CoV-2 proteins. These genes are involved in cellular signaling, metabolism, immune response and RNA homeostasis. Since lncRNAs have been known to sponge microRNAs and protect expression of upregulated genes, we also identified 9 microRNAs that are induced in viral infections; however, some lncRNAs are able to block their usual suppressive effect on overexpressed genes and consequently contribute to host defense and cell survival. Conclusions Our investigation determines that deregulated lncRNAs in SARS-CoV-2 infection are involved in viral proliferation, cellular survival, and immune response, ultimately determining disease outcome and this information could drive the search for novel RNA therapeutics as a treatment option. url: https://doi.org/10.1101/2020.06.29.177204 doi: 10.1101/2020.06.29.177204 id: cord-321050-yabt72jf author: Tuttle, Kathryn D. title: JAK1 inhibition blocks lethal sterile immune responses: implications for COVID-19 therapy date: 2020-04-09 words: 4121.0 sentences: 208.0 pages: flesch: 46.0 cache: ./cache/cord-321050-yabt72jf.txt txt: ./txt/cord-321050-yabt72jf.txt summary: Increasing evidence supports the notion that mortality during infections with SARS-CoV-2, which causes coronavirus disease of 2019 , is driven by the exacerbated immune response to the virus, leading to a cascade of events involving a cytokine storm and acute respiratory distress syndrome (ARDS), often accompanied by myocardial damage and multiple organ failure (5, 6) . Overall, these results have potential far-reaching significance for the treatment of COVID-19, justifying a deeper study of JAK inhibitors as a therapeutic strategy to attenuate the cytokine storm and downstream organ failure in this condition, while also indicating that individuals with DS should be considered a high-risk population during the COVID-19 pandemic. This analysis revealed that Dp16 mice have increased liver pathology even before P(I:C) treatment, as demonstrated by significantly higher levels of cell injury, inflammation, and reactive changes relative to their WT littermates (Figure 4B,C) . abstract: Cytokine storms are drivers of pathology and mortality in myriad viral infections affecting the human population. In SARS-CoV-2-infected patients, the strength of the cytokine storm has been associated with increased risk of acute respiratory distress syndrome, myocardial damage, and death. However, the therapeutic value of attenuating the cytokine storm in COVID-19 remains to be defined. Here, we report results obtained using a novel mouse model of lethal sterile anti-viral immune responses. Using a mouse model of Down syndrome (DS) with a segmental duplication of a genomic region encoding four of the six interferon receptor genes (Ifnrs), we demonstrate that these animals overexpress Ifnrs and are hypersensitive to IFN stimulation. When challenged with viral mimetics that activate Toll-like receptor signaling and IFN anti-viral responses, these animals overproduce key cytokines, show exacerbated liver pathology, rapidly lose weight, and die. Importantly, the lethal immune hypersensitivity, accompanying cytokine storm, and liver hyperinflammation are blocked by treatment with a JAK1-specific inhibitor. Therefore, these results point to JAK1 inhibition as a potential strategy for attenuating the cytokine storm and consequent organ failure during overdrive immune responses. Additionally, these results indicate that people with DS, who carry an extra copy of the IFNR gene cluster encoded on chromosome 21, should be considered at high risk during the COVID-19 pandemic. One Sentence Summary Inhibition of the JAK1 kinase prevents pathology and mortality caused by a rampant innate immune response in mice. url: https://doi.org/10.1101/2020.04.07.024455 doi: 10.1101/2020.04.07.024455 id: cord-260481-twk5kvd3 author: Täufer, Matthias title: Rapid, large-scale, and effective detection of COVID-19 via non-adaptive testing date: 2020-08-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Pooling of samples can increase lab capacity when using Polymerase chain reaction (PCR) to detect diseases such as COVID-19. However, pool testing is typically performed via an adaptive testing strategy which requires a feedback loop in the lab and at least two PCR runs to confirm positive results. This can cost precious time. We discuss a non-adaptive testing method where each sample is distributed in a prescribed manner over several pools, and which yields reliable results after one round of testing. More precisely, assuming knowledge about the overall incidence rate, we calculate explicit error bounds on the number of false positives which scale favourably with pool size and sample multiplicity. This allows for hugely streamlined PCR testing and cuts in detection times for a large-scale testing scenario. A viable consequence of this method could be real-time screening of entire communities, frontline healthcare workers and international flight passengers, for example, using the PCR machines currently in operation. url: https://doi.org/10.1101/2020.04.06.028431 doi: 10.1101/2020.04.06.028431 id: cord-292670-12prczym author: Urra, José Miguel title: The antibody response to the glycan α-Gal correlates with COVID-19 disease symptoms date: 2020-07-14 words: 2099.0 sentences: 115.0 pages: flesch: 44.0 cache: ./cache/cord-292670-12prczym.txt txt: ./txt/cord-292670-12prczym.txt summary: Humans evolved by losing the capacity to synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti-α-Gal IgM/IgG antibodies produced in response to bacterial microbiota. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with α-Gal epitopes to modify the microbiota and increase the α-Gal-induced protective immune response and reduce the severity of COVID-19. Although more severe symptoms have been associated with elderly patients, herein older 199 patients were recorded in the hospitalized and not the ICU group (p < 0.001; Table 1 The serum IgA, IgE, IgM and IgG antibody response to α-Gal was characterized in healthy 226 individuals and COVID-19 patients at different disease stages (Figures 2 and 3a) . abstract: The coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. The characterization of the immunological mechanisms involved in disease symptomatology and protective response is important to advance in disease control and prevention. Humans evolved by losing the capacity to synthesize the glycan Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal), which resulted in the development of a protective response against pathogenic viruses and other microorganisms containing this modification on membrane proteins mediated by anti-α-Gal IgM/IgG antibodies produced in response to bacterial microbiota. In addition to anti-α-Gal antibody-mediated pathogen opsonization, this glycan induces various immune mechanisms that have shown protection in animal models against infectious diseases without inflammatory responses. In this study, we hypothesized that the immune response to α-Gal may contribute to the control of COVID-19. To address this hypothesis, we characterized the antibody response to α-Gal in patients at different stages of COVID-19 and in comparison with healthy control individuals. The results showed that while the inflammatory response and the anti-SARS-CoV-2 (Spike) IgG antibody titers increased, reduction in anti-α-Gal IgE, IgM and IgG antibody titers and alteration of anti-α-Gal antibody isotype composition correlated with COVID-19 severity. The results suggested that the inhibition of the α-Gal-induced immune response may translate into more aggressive viremia and severe disease inflammatory symptoms. These results support the proposal of developing interventions such as probiotics based on commensal bacteria with α-Gal epitopes to modify the microbiota and increase the α-Gal-induced protective immune response and reduce the severity of COVID-19. url: https://doi.org/10.1101/2020.07.14.201954 doi: 10.1101/2020.07.14.201954 id: cord-102661-lh7992rl author: Valentine, Charles C. title: Direct Quantification of in vivo Mutagenesis and Carcinogenesis Using Duplex Sequencing date: 2020-11-03 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The ability to accurately measure mutations is critical for basic research and identification of potential drug and chemical carcinogens. Current methods for in vivo quantification of mutagenesis are limited because they rely on transgenic rodent systems that are low-throughput, expensive, prolonged, and don’t fully represent other species such as humans. Next generation sequencing (NGS) is a conceptually attractive alternative for mutation detection in the DNA of any organism, however, the limit of resolution for standard NGS is poor. Technical error rates (~1×10−3) of NGS obscure the true abundance of somatic mutations, which can exist at pernucleotide frequencies ≤1×10−7. Using Duplex Sequencing, an extremely accurate error-corrected NGS (ecNGS) technology, we were able to detect mutations induced by 3 carcinogens in 5 tissues of 2 strains of mice within 31 days following exposure. We observed a strong correlation between mutation induction measured by Duplex Sequencing and the gold-standard transgenic rodent mutation assay. We identified exposure-specific mutation spectra of each compound through trinucleotide patterns of base substitution. We observed variation in mutation susceptibility by genomic region, as well as by DNA strand. We also identified the primordial signs of carcinogenesis in a cancer-predisposed strain of mice, as evidenced by clonal expansions of cells carrying an activated oncogene, less than a month after carcinogen exposure. These findings demonstrate that ecNGS is a powerful method for sensitively detecting and characterizing mutagenesis and the early clonal evolutionary hallmarks of carcinogenesis. Duplex Sequencing can be broadly applied to chemical safety testing, basic mutational research, and related clinical uses. SIGNIFICANCE STATEMENT Error-corrected next generation sequencing (ecNGS) can be used to rapidly detect and quantify the in vivo mutagenic impact of environmental exposures or endogenous processes in any tissue, from any species, at any genomic location. The greater speed, higher scalability, richer data outputs, as well as cross-species and cross-locus applicability of ecNGS compared to existing methods make it a powerful new tool for mutational research, regulatory safety testing, and emerging clinical applications. url: https://doi.org/10.1101/2020.06.28.176685 doi: 10.1101/2020.06.28.176685 id: cord-103181-my4n0vye author: Valle-Casuso, José Carlos title: Replication of Equine arteritis virus is efficiently suppressed by purine and pyrimidine biosynthesis inhibitors date: 2020-04-10 words: 2171.0 sentences: 115.0 pages: flesch: 47.0 cache: ./cache/cord-103181-my4n0vye.txt txt: ./txt/cord-103181-my4n0vye.txt summary: Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. We were also interested in exploring the antiviral capacity of two new BSA, IPPA17-04 and GAC50 163 that impair viral replication through inhibition of de novo pyrimidine biosynthesis in host cells. These results show that cell cultures treated with pyrimidine biosynthesis inhibitors did not 175 exhibit cytopathic effects associated to EAV infection, suggesting that EAV replication is also impaired. To verify that ribavirin, IPPA17-A04 and GAC50 actually block EAV replication, viral genome copies 180 were quantified at 48 h.p.i. Culture supernatants of infected ED cells treated or not with the 181 compounds at different concentrations were analyzed by RT-qPCR. abstract: RNA viruses are responsible for a large variety of animal infections. Equine Arteritis Virus (EAV) is a positive single-stranded RNA virus member of the family Arteriviridae from the order Nidovirales like the Coronaviridae. EAV causes respiratory and reproductive diseases in equids. Although two vaccines are available, the vaccination coverage of the equine population is largely insufficient to prevent new EAV outbreaks around the world. In this study, we present a high-throughput in vitro assay suitable for testing candidate antiviral molecules on equine dermal cells infected by EAV. Using this assay, we identified three molecules that impair EAV infection in equine cells: the broad-spectrum antiviral and nucleoside analog ribavirin, and two compounds previously described as inhibitors of dihydroorotate dehydrogenase (DHODH), the fourth enzyme of the pyrimidine biosynthesis pathway. These molecules effectively suppressed cytopathic effects associated to EAV infection, and strongly inhibited viral replication and production of infectious particles. Since ribavirin is already approved in human and small animal, and that several DHODH inhibitors are in advanced clinical trials, our results open new perspectives for the management of EAV outbreaks. url: https://doi.org/10.1101/2020.04.10.035402 doi: 10.1101/2020.04.10.035402 id: cord-103567-nh9i28lu author: Vanachayangkul, Pattaraporn title: Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques date: 2020-04-29 words: 3686.0 sentences: 193.0 pages: flesch: 62.0 cache: ./cache/cord-103567-nh9i28lu.txt txt: ./txt/cord-103567-nh9i28lu.txt summary: title: Safety, pharmacokinetics, and liver-stage Plasmodium cynomolgi effect of high-dose ivermectin and chloroquine in Rhesus Macaques Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (IC50 = 10.42 μM) and hypnozoites (IC50 = 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for seven consecutive days was evaluated for prophylaxis or radical cure of Plasmodium cynomolgi liver-stages in Rhesus macaques. Approximately 3 weeks later, a second relapse occurred 174 in all negative control and ivermectin high-and low-dose treated macaques with no significant 175 differences for time to blood-stage parasitemia or treatment (Log-Rank (Mantel Cox) test P > 176 0.05). If a relapse occurs, 397 and blood-stage parasitemia reaches >5,000 parasites per µl, then macaques received seven 398 days of chloroquine (10mg/kg) plus ivermectin (1.2 mg/kg) for both the low-and high-dose 399 groups. abstract: Previously, ivermectin (1–10 mg/kg) was shown to inhibit liver-stage development of Plasmodium berghei in orally dosed mice. Here, ivermectin showed inhibition of the in vitro development of Plasmodium cynomolgi schizonts (IC50 = 10.42 μM) and hypnozoites (IC50 = 29.24 μM) in primary macaque hepatocytes when administered in high-dose prophylactically but not when administered in radical cure mode. The safety, pharmacokinetics, and efficacy of oral ivermectin (0.3, 0.6, and 1.2 mg/kg) with and without chloroquine (10 mg/kg) administered for seven consecutive days was evaluated for prophylaxis or radical cure of Plasmodium cynomolgi liver-stages in Rhesus macaques. No inhibition or delay to blood-stage P. cynomolgi parasitemia was observed at any ivermectin dose (0.3, 0.6, and 1.2 mg/kg). Ivermectin (0.6 and 1.2 mg/kg) and chloroquine (10 mg/kg) in combination were well-tolerated with no adverse events and no significant pharmacokinetic drug-drug interactions observed. Repeated daily ivermectin administration for seven days did not inhibit ivermectin bioavailability. It was recently demonstrated that both ivermectin and chloroquine inhibit replication of the novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in vitro. Further ivermectin and chloroquine trials in humans are warranted to evaluate their role in Plasmodium vivax control and as adjunctive therapies against COVID-19 infections. url: https://doi.org/10.1101/2020.04.27.065409 doi: 10.1101/2020.04.27.065409 id: cord-103108-vmze2mdx author: Vanheer, Lotte title: Revealing the Key Regulators of Cell Identity in the Human Adult Pancreas date: 2020-09-25 words: 7967.0 sentences: 440.0 pages: flesch: 47.0 cache: ./cache/cord-103108-vmze2mdx.txt txt: ./txt/cord-103108-vmze2mdx.txt summary: HIGHLIGHTS Reconstruction of gene regulatory networks for human adult pancreatic cell types An interactive resource to explore and visualize gene expression and regulatory states Predicting putative transcription factors driving pancreatic cell identity HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively Because TFs recognize DNA motifs in the genome, one can measure if inferred target genes are expressed within single cells, and therefore quantify the activity of TFs. Such approaches have revealed the regulatory programs in distinct systems including the Drosophila brain (Davie et al , 2018) , cancer (Wouters et al., 2020) , during early mouse embryonic development (Peng et al , 2019) , in a mouse cell atlas (Suo et al., 2018 ) and a human cell atlas (Han et al., 2020) . abstract: Cellular identity during development is under the control of transcription factors that form gene regulatory networks. However, the transcription factors and gene regulatory networks underlying cellular identity in the human adult pancreas remain largely unexplored. Here, we integrate multiple single-cell RNA sequencing datasets of the human adult pancreas, totaling 7393 cells, and comprehensively reconstruct gene regulatory networks. We show that a network of 142 transcription factors forms distinct regulatory modules that characterize pancreatic cell types. We present evidence that our approach identifies key regulators of cell identity in the human adult pancreas. We predict that HEYL and JUND are active in acinar and alpha cells, respectively, and show that these proteins are present in the human adult pancreas as well as in human induced pluripotent stem cell-derived pancreatic cells. The comprehensive gene regulatory network atlas can be explored interactively online. We anticipate our analysis to be the starting point for a more sophisticated dissection of how transcription factors regulate cell identity in the human adult pancreas. Furthermore, given that transcription factors are major regulators of embryo development and are often perturbed in diseases, a comprehensive understanding of how transcription factors work will be relevant in development and disease biology. HIGHLIGHTS - Reconstruction of gene regulatory networks for human adult pancreatic cell types - An interactive resource to explore and visualize gene expression and regulatory states - Predicting putative transcription factors driving pancreatic cell identity - HEYL and JUND as candidate regulators of acinar and alpha cell identity, respectively url: https://doi.org/10.1101/2020.09.23.310094 doi: 10.1101/2020.09.23.310094 id: cord-351472-ch004jxy author: Vashi, Yoya title: Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens date: 2020-04-10 words: 1335.0 sentences: 161.0 pages: flesch: 71.0 cache: ./cache/cord-351472-ch004jxy.txt txt: ./txt/cord-351472-ch004jxy.txt summary: The present study followed computational approaches to identify Band T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics. We identified 18 linear epitopes, predicted by ElliPro (IEDB), which contains regions from 128 19 of our selected peptides highlighted in red in Table 2 . Using the same module, B-cell discontinuous epitopes were predicted, which gave 16 133 epitope regions that contained regions from 18 of our selected peptides highlighted in red 134 (Table 3) . Regions from all of our selected peptides were found to be potential T-cell 7 epitope(s) with high binding affinity with HLA-A and HLA-B alleles, except one. IEDB ElliPro predicted discontinuous epitopes for spike protein of SARS-CoV-2. abstract: The 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface. Out of which twenty are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics. url: https://doi.org/10.1101/2020.04.08.013516 doi: 10.1101/2020.04.08.013516 id: cord-334300-hnrmaytm author: Ventura Fernandes, Bianca H title: Zebrafish studies on the vaccine candidate to COVID-19, the Spike protein: Production of antibody and adverse reaction date: 2020-10-20 words: 1799.0 sentences: 126.0 pages: flesch: 50.0 cache: ./cache/cord-334300-hnrmaytm.txt txt: ./txt/cord-334300-hnrmaytm.txt summary: Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus. 169 In the global task to develop the vaccine and possible therapeutic approaches for 170 COVID-19, several animal models have been proposed, such as mice 10 , hACE2 171 transgenic mice 11 , alpaca 12 , golden Syrian hamsters, ferrets, dogs, pigs, chickens, and 172 cats 9 , and species of non-human primates 10 . abstract: Establishing new experimental animal models to assess the safety and immune response to the antigen used in the development of COVID-19 vaccine is an imperative issue. Based on the advantages of using zebrafish as a model in research, herein we suggest doing this to test the safety of the putative vaccine candidates and to study immune response against the virus. We produced a recombinant N-terminal fraction of the Spike SARS-CoV-2 protein and injected it into adult female zebrafish. The specimens generated humoral immunity and passed the antibodies to the eggs. However, they presented adverse reactions and inflammatory responses similar to severe cases of human COVID-19. The analysis of the structure and function of zebrafish and human Angiotensin-converting enzyme 2, the main human receptor for virus infection, presented remarkable sequence similarities. Moreover, bioinformatic analysis predicted protein-protein interaction of the Spike SARS-CoV-2 fragment and the Toll-like receptor pathway. It might help in the choice of future therapeutic pharmaceutical drugs to be studied. Based on the in vivo and in silico results presented here, we propose the zebrafish as a model for translational research into the safety of the vaccine and the immune response of the vertebrate organism to the SARS-CoV-2 virus. url: https://doi.org/10.1101/2020.10.20.346262 doi: 10.1101/2020.10.20.346262 id: cord-103652-yjl7uj2h author: Vickaryous, Nicola title: Remote testing of vitamin D levels across the UK MS population – a case control study date: 2020-10-16 words: 3259.0 sentences: 183.0 pages: flesch: 52.0 cache: ./cache/cord-103652-yjl7uj2h.txt txt: ./txt/cord-103652-yjl7uj2h.txt summary: Data including baseline serum 25(OH)D levels, vitamin D supplementation (yes/no; no dose information available), oily fish consumption, time spent outdoors and UV sun protection usage were analysed. 72% (276/386) of the MS participants from the biological sampling group reported taking vitamin D supplements compared to 26% (79/305) of controls (p<0.001; Table 2 ). A lower proportion of people with MS took vitamin D supplementation at UKBB enrolment than in our current study, however they were still more likely to do so than the matched controls (14% vs 6%, p<0.001) (Supplementary table 5 ). Not only were MS participants more likely to take vitamin D supplements, but they also took them at higher doses, such that people with MS in the UK now have overall higher serum 25(OH)D levels than controls. Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study abstract: Objective The association between vitamin D deficiency and multiple sclerosis (MS) is well described. We set out to use remote sampling to ascertain vitamin D status and vitamin D supplementation in a cross-sectional study of people with MS across the UK. Methods People with MS and matched controls were recruited from across the UK. 1768 people with MS enrolled in the study; remote sampling kits were distributed to a subgroup. Dried blood spots (DBS) were used to assess serum 25(OH)D in people with MS and controls. Results 1768 MS participants completed the questionnaire; 388 MS participants and 309 controls provided biological samples. Serum 25(OH)D was higher in MS than controls (median 71nmol/L vs 49nmol/L). A higher proportion of MS participants than controls supplemented (72% vs 26%, p<0.001); people with MS supplemented at higher vD doses than controls (median 1600 vs 600 IU/day, p<0.001). People with MS who did not supplement had lower serum 25(OH)D levels than non-supplementing controls (median 38 nmol/L vs 44 nmol/L). Participants engaged well with remote sampling. Conclusions The UK MS population have higher serum 25(OH)D than controls, mainly as a result of vitamin D supplementation. Remote sampling is a feasible way of carrying out large studies. url: https://doi.org/10.1101/2020.10.16.342253 doi: 10.1101/2020.10.16.342253 id: cord-284102-rovyvv45 author: Wagner, Teresa R. title: NeutrobodyPlex - Nanobodies to monitor a SARS-CoV-2 neutralizing immune response date: 2020-09-28 words: 2910.0 sentences: 190.0 pages: flesch: 53.0 cache: ./cache/cord-284102-rovyvv45.txt txt: ./txt/cord-284102-rovyvv45.txt summary: Here we identified 11 unique nanobodies (Nbs) with high binding affinities to the SARS-CoV-2 spike receptor domain (RBD). Considering that Nbs targeting diverse epitopes within the RBD:ACE2 interface are beneficial 201 in both reducing viral infectivity and preventing mutational escape, we next combined the most 202 potent inhibitory and neutralizing candidates derived from Nb-Set1 (NM1226, NM1228) and 203 We incubated our previously generated color-coded beads 232 comprising RBD, S1 domain or homotrimeric spike with serum samples from patients or non-233 infected individuals, in addition to dilution series of the combinations NM1226/ NM1230 or 234 NM1228/ NM1230 and used this to detect patient-derived IgGs bound to the respective 235 antigens. As a result, we modified our previously described multiplex immunoassay 303 (MULTICOV-AB, 20 ) and developed a novel diagnostic test called NeutrobodyPlex to monitor 304 the presence and the emergence of neutralizing antibodies in serum samples of SARS-CoV-2 305 infected individuals. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block 681 interaction with ACE2 abstract: As the COVID-19 pandemic escalates, the need for effective vaccination programs, diagnosis tools and therapeutic intervention ever increases. Neutralizing binding molecules have become important tools for acute treatment of COVID-19 and also provide a unique possibility to monitor the emergence and presence of a neutralizing immune response in infected or vaccinated individuals. Here we identified 11 unique nanobodies (Nbs) with high binding affinities to the SARS-CoV-2 spike receptor domain (RBD). Of these, 8 effectively block the RBD:ACE2 interface. Via competitive binding analysis and detailed epitope mapping, we grouped all Nbs into 3 sets and demonstrated their neutralizing effect. Combinations from different sets showed a profound synergistic effect by simultaneously targeting different epitopes within the RBD. Finally, we established a competitive multiplex binding assay (“NeutrobodyPlex”) enabling the detection of neutralizing antibodies in serum of infected patients. Overall, our Nbs have high potential for prophylactic and therapeutic options and provide a novel approach to screen for a neutralizing immune response in infected or vaccinated individuals, helping to monitor immune status or guide vaccine design. url: https://doi.org/10.1101/2020.09.22.308338 doi: 10.1101/2020.09.22.308338 id: cord-261855-qpbgq5d8 author: Walker, Susanne N. title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients date: 2020-06-18 words: 2533.0 sentences: 166.0 pages: flesch: 57.0 cache: ./cache/cord-261855-qpbgq5d8.txt txt: ./txt/cord-261855-qpbgq5d8.txt summary: title: SARS-CoV-2 assays to detect functional antibody responses that block ACE2 recognition in vaccinated animals and infected patients Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients. Here, we describe a competition ELISA assay and a SPR 100 assay developed to rapidly detect ACE2 receptor blocking antibodies in IgGs and sera of 101 vaccinated mice, guinea pigs, rabbits and non-human primates, as well as, human samples (Fig. 1B) . Next, using Enzyme-Linked Immunosorbent Assays (ELISAs) we immobilized full-length 120 SARS-CoV-2 spike protein (containing both the S1 and S2 subunits) and incubated a dilution 121 series of ACE2-IgHu (Fig. 1D) . The proof-of-concept competition ELISA displayed a full blocking curve, so we sought to utilize 140 this assay for animals immunized with SARS-CoV-2 spike protein. abstract: SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has caused a global pandemic of COVID-19 resulting in cases of mild to severe respiratory distress and significant mortality. The global outbreak of this novel coronavirus has now infected >8 million people worldwide with >2 million cases in the US (June 17th, 2020). There is an urgent need for vaccines and therapeutics to combat the spread of this coronavirus. Similarly, the development of diagnostic and research tools to determine infection and vaccine efficacy are critically needed. Molecular assays have been developed to determine viral genetic material present in patients. Serological assays have been developed to determine humoral responses to the spike protein or receptor binding domain (RBD). Detection of functional antibodies can be accomplished through neutralization of live SARS-CoV2 virus, but requires significant expertise, an infectible stable cell line, a specialized BioSafety Level 3 (BSL-3) facility. As large numbers of people return from quarantine, it is critical to have rapid diagnostics that can be widely adopted and employed to assess functional antibody levels in the returning workforce. This type of surrogate neutralization diagnostic can also be used to assess humoral immune responses induced in patients from the large number of vaccine and immunotherapy trials currently on-going. Here we describe a rapid serological diagnostic assay for determining antibody receptor blocking and demonstrate the broad utility of the assay by measuring the antibody functionality of sera from small animals and non-human primates immunized with an experimental SARS-CoV-2 vaccine and using sera from infected patients. url: https://doi.org/10.1101/2020.06.17.158527 doi: 10.1101/2020.06.17.158527 id: cord-308428-zw26usmh author: Walter, Justin D. title: Highly potent bispecific sybodies neutralize SARS-CoV-2 date: 2020-11-10 words: 10526.0 sentences: 580.0 pages: flesch: 54.0 cache: ./cache/cord-308428-zw26usmh.txt txt: ./txt/cord-308428-zw26usmh.txt summary: Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We identified a sybody pair (Sb#15 and Sb#68) that can bind simultaneously to the RBD, and block ACE2 binding, thereby neutralizing pseudotyped and live SARS-CoV-2 viruses. However, binders of the isolated RBD may not effectively engage the aforementioned pre-fusion conformation of the spike protein, which could account for the poor neutralization ability of recently described single-domain antibodies that were raised against the RBD of SARS-CoV-2 spike protein [29] . Since Sb#15 and Sb#68 can bind simultaneously to the RBD and the full-length spike protein, we mixed Sb#15 and Sb#68 together to investigate potential additive or synergistic neutralizing activity of these two independent sybodies. To gain structural insights into how Sb#15 and Sb#68 recognize the RBD, we performed single particle cryo-EM analysis of the spike protein in complex with the sybodies. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 abstract: The COVID-19 pandemic has resulted in a global crisis. Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2 spike protein. We identified a sybody pair (Sb#15 and Sb#68) that can bind simultaneously to the RBD, and block ACE2 binding, thereby neutralizing pseudotyped and live SARS-CoV-2 viruses. Cryo-EM analyses of the spike protein in complex with both sybodies revealed symmetrical and asymmetrical conformational states. In the symmetric complex each of the three RBDs were bound by both sybodies, and adopted the up conformation. The asymmetric conformation, with three Sb#15 and two Sb#68 bound, contained one down RBD, one up-out RBD and one up RBD. Bispecific fusions of the sybodies increased the neutralization potency 100-fold, as compared to the single binders. Our work demonstrates that linking two binders that recognize spatially-discrete binding sites result in highly potent SARS-CoV-2 inhibitors for potential therapeutic applications. url: https://doi.org/10.1101/2020.11.10.376822 doi: 10.1101/2020.11.10.376822 id: cord-318444-sgm24q1i author: Walter, Justin D. title: Sybodies targeting the SARS-CoV-2 receptor-binding domain date: 2020-05-16 words: 5902.0 sentences: 416.0 pages: flesch: 49.0 cache: ./cache/cord-318444-sgm24q1i.txt txt: ./txt/cord-318444-sgm24q1i.txt summary: Two independently prepared RBD constructs were used for in vitro sybody selections, and resulting single clones that could bind the full spike ectodomain were sequenced, expressed, and purified. Six unique sybodies show favorable binding affinity to the SARS-CoV-2 spike, and five of these were also found to substantially attenuate the interaction between the viral RBD and human ACE2. While this purified pre-fusion spike (PFS) had not yet been available for binder selections and characterization by grating-coupled interferometry, it was used to conduct ELISAs in order to identify selected sybodies which recognize the RBD in the pre-fusion context (see below). Since virulence of SARS-CoV-2 is dependent on the ability of the viral RBD to bind to human ACE2 (hACE2), we sought to determine which of the 57 selected sybodies that were well-behaved upon purification could inhibit interaction between the isolated RBD and purified hACE2. abstract: The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has resulted in a global health and economic crisis of unprecedented scale. The high transmissibility of SARS-CoV-2, combined with a lack of population immunity and prevalence of severe clinical outcomes, urges the rapid development of effective therapeutic countermeasures. Here, we report the generation of synthetic nanobodies, known as sybodies, against the receptor-binding domain (RBD) of SARS-CoV-2. In an expeditious process taking only twelve working days, sybodies were selected entirely in vitro from three large combinatorial libraries, using ribosome and phage display. We obtained six strongly enriched sybody pools against the isolated RBD and identified 63 unique anti-RBD sybodies which also interact in the context of the full-length SARS-CoV-2 spike ectodomain. Among the selected sybodies, six were found to bind to the viral spike with double-digit nanomolar affinity, and five of these also showed substantial inhibition of RBD interaction with human angiotensin-converting enzyme 2 (ACE2). Additionally, we identified a pair of anti-RBD sybodies that can simultaneously bind to the RBD. It is anticipated that compact binders such as these sybodies could feasibly be developed into an inhalable drug that can be used as a convenient prophylaxis against COVID-19. Moreover, generation of polyvalent antivirals, via fusion of anti-RBD sybodies to additional small binders recognizing secondary epitopes, could enhance the therapeutic potential and guard against escape mutants. We present full sequence information and detailed protocols for the identified sybodies, as a freely accessible resource. url: https://doi.org/10.1101/2020.04.16.045419 doi: 10.1101/2020.04.16.045419 id: cord-285088-krim73zt author: Wang, Deguo title: One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay date: 2020-04-21 words: 1792.0 sentences: 82.0 pages: flesch: 57.0 cache: ./cache/cord-285088-krim73zt.txt txt: ./txt/cord-285088-krim73zt.txt summary: title: One-pot Detection of COVID-19 with Real-time Reverse-transcription Loop-mediated Isothermal Amplification (RT-LAMP) Assay and Visual RT-LAMP Assay Objective This study was to establish one-pot real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay and one-pot visual RT-LAMP assay for the detection of COVID-19. The analytic sensitivities of the newly developed real-time RT-LAMP assay and visual RT-LAMP assay were determined with pUC57-N DNA ranging from 2-0.02 fg, and the reaction mixtures were heated at the optimal temperature for 60 min in a StepOneTM System (Applied Biosystems, Foster City, CA, USA) or in a water bath, when water bath was used, the reaction tube was sunk into water. The detection limits of the one-pot real-time RT-LAMP assay and the one-pot visual RT-LAMP assay were determined using pUC57-N DNA ranging from 2-0.02 fg at 59 °C for 60 min in a StepOneTM System (Applied Biosystems, Foster City, CA, USA) or in a water bath. abstract: Background Rapid and reliable diagnostic assays were critical for prevention and control of the coronavirus pneumonia caused by COVID-19. Objective This study was to establish one-pot real-time reverse-transcription loop-mediated isothermal amplification (RT-LAMP) assay and one-pot visual RT-LAMP assay for the detection of COVID-19. Methods Six specific LAMP primers targeting the N gene of COVID-19 were designed, the RT-LAMP reaction system was optimized with plasmid pUC57 containing N gene sequence, the detection limit was determined with a serial dilution of the plasmid pUC57 containing N gene sequence, and the one-pot real-time RT-LAMP assay and one-pot visual RT-LAMP assay for the detection of COVID-19 were established. Results Our results showed that the one-pot RT-LAMP assays can detect COVID-19 with a limit of ≥ 6 copies per μl−1 of pUC57 containing N gene sequence. Conclusion This study provides rapid, reliable and sensitive tools for facilitating preliminary and cost-effective prevention and control of COVID-19. url: https://doi.org/10.1101/2020.04.21.052530 doi: 10.1101/2020.04.21.052530 id: cord-320417-01l27d99 author: Wang, Hai-Long title: The emergence of inter-clade hybrid SARS-CoV-2 lineages revealed by 2D nucleotide variation mapping date: 2020-10-14 words: 5013.0 sentences: 257.0 pages: flesch: 52.0 cache: ./cache/cord-320417-01l27d99.txt txt: ./txt/cord-320417-01l27d99.txt summary: I proposed a novel illustrating method using a 2D map to display populations of co-occurring nucleotide variants for intraand inter-viral clades. Using this method, I revealed the emergence of inter-clade hybrid SARS-CoV-2 lineages that are potentially caused by homologous genetic recombination. SARS-CoV-2 is an RNA virus with limited genome length, but its high mutation rate and homologous genetic recombination nonetheless gave rise to exponentially increased variants. This is why all previously reported recombination events of SARS-Cov-2 have relied on clade-defining SNPs. The 2D co-occurring variant mapping is a simple way to display inter-clade hybrid lineages, and it can be used to directly compare distributions of populations for intra-and inter-clade from different geographic locations or the same location but at a different time point. I downloaded ~18,000 SARS-CoV-2 genome sequences from NCBI (on September 2 nd ) and used the same criterion as before to search for inter-clade co-occurring SNP pairs (see method for details). abstract: I performed whole-genome sequencing on SARS-CoV-2 collected from COVID-19 samples at Mayo Clinic Rochester in mid-April, 2020, generated 85 consensus genome sequences and compared them to other genome sequences collected worldwide. I proposed a novel illustrating method using a 2D map to display populations of co-occurring nucleotide variants for intra- and inter-viral clades. This method is highly advantageous for the new era of “big-data” when high-throughput sequencing is becoming readily available. Using this method, I revealed the emergence of inter-clade hybrid SARS-CoV-2 lineages that are potentially caused by homologous genetic recombination. url: https://doi.org/10.1101/2020.10.13.338038 doi: 10.1101/2020.10.13.338038 id: cord-103648-g50g17ti author: Wang, Hao-Yuan title: Total synthesis and biological characterization of SR-A3, a ternatin-related eEF1A inhibitor with enhanced cellular residence time date: 2020-10-08 words: 2175.0 sentences: 124.0 pages: flesch: 48.0 cache: ./cache/cord-103648-g50g17ti.txt txt: ./txt/cord-103648-g50g17ti.txt summary: Ternatin and related cyclic peptides inhibit the elongation phase of protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A), a potential therapeutic vulnerability in cancer and viral infections. Based on our hypothesis that A3 is structurally related to the anti-adipogenic cyclic heptapeptide, ternatin, 9 we previously designed and synthesized "ternatin-4", which incorporates the dehydromethyl leucine (dhML) and pipecolic acid residues found in A3, yet lacks the b-hydroxy group attached to N-Me-Leu ( Figure 1 ). Similar to ternatin-4, SR-A3 potently inhibited cell proliferation and protein synthesis by targeting eEF1A. Whereas protein synthesis rates partially recovered in cells treated with ternatin-4 or SS-A3 (~30% of DMSO control levels, 24 h post-washout), transient exposure of cells to SR-A3 resulted in sustained inhibition (Figure 6a ). Rather, SR-A3 exhibits a dramatic increase in cellular residence time, as revealed by washout experiments followed by assessment of protein synthesis and cell proliferation rates. abstract: Ternatin and related cyclic peptides inhibit the elongation phase of protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A), a potential therapeutic vulnerability in cancer and viral infections. The cyclic peptide natural product “A3” appears to be related to ternatin, but its complete structure is unknown and only 4 of its 11 stereocenters have been assigned. Hence, A3 could be any one of 128 possible stereoisomers. Guided by the stereochemistry of ternatin and more potent structural variants, we synthesized two A3 epimers, “SR-A3” and “SS-A3”. We found that synthetic SR-A3 is indistinguishable from naturally derived A3 and potently inhibits cancer cell proliferation. Relative to SS-A3 and previously characterized ternatin variants, SR-A3 exhibits a dramatically enhanced duration of action. This increase in cellular residence time is conferred, stereospecifically, by a single β-hydroxy group attached to N-methyl leucine. SR-A3 thus exemplifies a mechanism for enhancing the pharmacological potency of cyclic peptide natural products via side-chain hydroxylation. url: https://doi.org/10.1101/2020.10.06.325498 doi: 10.1101/2020.10.06.325498 id: cord-260508-z11exbyu author: Wang, Hongru title: Synonymous mutations and the molecular evolution of SARS-Cov-2 origins date: 2020-10-12 words: 4698.0 sentences: 272.0 pages: flesch: 58.0 cache: ./cache/cord-260508-z11exbyu.txt txt: ./txt/cord-260508-z11exbyu.txt summary: Phylogenetic analyses (Fig. 2 ) in genomic regions with all recombination tracts 6 (Supplementary Table 5 ) masked using Maximum-likelihood (Fig. 2a) and Neighbor-joining 7 based on synonymous (Fig. 2b ) or non-synoymous (Fig. 2c ) mutation distance metrics, 8 consistently support RmYN02 as the nearest outgroup to human SARS-CoV-2, in contrast to 9 previous analyses before the discovery of RmYN02, which instead found RaTG13 to be the 10 nearest outgroup ). Notice that the divergences 14 between human SARS-CoV-2 and the bat viral sequences, RaTG13 and RmYN02, in most 15 regions of the genome, are quite low compared to the other comparisons. While the overall divergence in the S gene encoding the spike protein could suggest the 10 presence of recombination in the region, previous study ) reported that the tree 11 based on synonymous substitutions supported RaTG13 as the sister taxon to the human SARS-12 abstract: Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively. url: https://doi.org/10.1101/2020.04.20.052019 doi: 10.1101/2020.04.20.052019 id: cord-103688-n7hzpbyf author: Wang, Lina title: VirusDIP: Virus Data Integration Platform date: 2020-06-09 words: 1286.0 sentences: 81.0 pages: flesch: 47.0 cache: ./cache/cord-103688-n7hzpbyf.txt txt: ./txt/cord-103688-n7hzpbyf.txt summary: Results To facilitate virus research and promote the global sharing of virus data, we present here VirusDIP, a one-stop service platform for archive, integration, access, analysis of virus data. It accepts the submission of viral sequence data from all over the world and currently integrates data resources from the National GeneBank Database (CNGBdb), Global initiative on sharing all influenza data (GISAID), and National Center for Biotechnology Information (NCBI). Moreover, based on the comprehensive data resources, BLAST sequence alignment tool and multi-party security computing tools are deployed for multi-sequence alignment, phylogenetic tree building and global trusted sharing. For data compatibility, the virus data standard integrates the virus and pathogen sample data standard of The International Nucleotide Sequence Database Collaboration (INSDC) (Karsch-Mizrachi et al., 2018) , the hCoV-19 data standard of GISAID, and the sample data standard of COVID-19 Genomics UK (COG-UK) Consortium. VirusDIP is committed to building a comprehensive virus data platform for archive, integration, access, and analysis. abstract: Motivation The Coronavirus Disease 2019 (COVID-19) pandemic poses a huge threat to human public health. Viral sequence data plays an important role in the scientific prevention and control of epidemics. A comprehensive virus database will be vital useful for virus data retrieval and deep analysis. To promote sharing of virus data, several virus databases and related analyzing tools have been created. Results To facilitate virus research and promote the global sharing of virus data, we present here VirusDIP, a one-stop service platform for archive, integration, access, analysis of virus data. It accepts the submission of viral sequence data from all over the world and currently integrates data resources from the National GeneBank Database (CNGBdb), Global initiative on sharing all influenza data (GISAID), and National Center for Biotechnology Information (NCBI). Moreover, based on the comprehensive data resources, BLAST sequence alignment tool and multi-party security computing tools are deployed for multi-sequence alignment, phylogenetic tree building and global trusted sharing. VirusDIP is gradually establishing cooperation with more databases, and paving the way for the analysis of virus origin and evolution. All public data in VirusDIP are freely available for all researchers worldwide. Availability https://db.cngb.org/virus/ Contact weixiaofeng@cngb.org url: https://doi.org/10.1101/2020.06.08.139451 doi: 10.1101/2020.06.08.139451 id: cord-263780-8jejswuk author: Wang, Nan title: Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus date: 2020-08-14 words: 1584.0 sentences: 103.0 pages: flesch: 66.0 cache: ./cache/cord-263780-8jejswuk.txt txt: ./txt/cord-263780-8jejswuk.txt summary: title: Chloroquine and hydroxychloroquine as ACE2 blockers to inhibit viropexis of 2019-nCoV Spike pseudotyped virus Purpose The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. Conclusions CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. In this study, we found that CQ and HCQ can antagonize ACE2 and inhibit the entry of 2019-nCoV 103 spike pseudotyped virus into ACE2 expressed HEK293T cells (ACE2 h cells). It can be concluded that the toxicity 216 of HCQ was higher than that of CQ on ACE2 h cells at different time points at the same 217 concentrations (Figure 1C) . abstract: Background The novel coronavirus disease (2019-nCoV) has been affecting global health since the end of 2019 and there is no sign that the epidemic is abating. The major issue for controlling the infectious is lacking efficient prevention and therapeutic approaches. Chloroquine (CQ) and Hydroxychloroquine (HCQ) have been reported to treat the disease, but the underlying mechanism remains controversial. Purpose The objective of this study is to investigate whether CQ and HCQ could be ACE2 blockers and used to inhibit 2019-nCoV virus infection. Methods In our study, we used CCK-8 staining, flow cytometry and immunofluorescent staining to evaluate the toxicity and autophagy of CQ and HCQ, respectively, on ACE2 high-expressing HEK293T cells (ACE2h cells). We further analyzed the binding character of CQ and HCQ to ACE2 by molecular docking and surface plasmon resonance (SPR) assays, 2019-nCoV spike pseudotyped virus was also used to observe the viropexis effect of CQ and HCQ in ACE2h cells. Results Results showed that HCQ is slightly more toxic to ACE2h cells than CQ. Both CQ and HCQ could bind to ACE2 with KD =(7.31±0.62)e−7 M and (4.82±0.87)e−7 M, respectively. They exhibit equivalent suppression effect for the entrance of 2019-nCoV spike pseudotyped virus into ACE2h cells. Conclusions CQ and HCQ both inhibit the entrance 2019-nCoV into cells by blocking the binding of the virus with ACE2. Our findings provide novel insights into the molecular mechanism of CQ and HCQ treatment effect on virus infection. url: https://doi.org/10.1101/2020.06.22.164665 doi: 10.1101/2020.06.22.164665 id: cord-103462-z3d9lcar author: Wang, Shiyu title: CD4+ T cell subsets present stable relationships in their T cell receptor repertoires date: 2020-11-02 words: 2934.0 sentences: 158.0 pages: flesch: 59.0 cache: ./cache/cord-103462-z3d9lcar.txt txt: ./txt/cord-103462-z3d9lcar.txt summary: Here, we examined the features of TCR beta (TCRB) repertoire of the top clones within naïve, memory and regular T cell (Treg) subsets: repertoire structure, gene usage, length distribution and sequence composition. To unveil the influence of differentiation on TCR repertoire, we analyzed the sequencing 68 data of TCR beta (TCRB) chain of NT, ET, EMT, CMT, Tscm and Treg. It suggests 232 that the length distribution of TCRB repertoire of NT is highly skewed in these less-233 differentiated memory cells ( Figure 4B ). We detected the 320 relationships among the TCRB repertoire of top1000 clones of naïve, memory and Treg subsets 321 (including NT, ET, Tcm, Tem, Tscm ET and Treg) by estimating the repertoire structure, the 322 germline gene usage, the sequence composition (K-mer) and public CDR3 clone usage. In our study, public clones from NT are less maintained in 359 differentiated subsets, and SVM analyses indicate that sequence composition in memory 360 abstract: CD4+ T cells are key components of adaptive immunity. The cell differentiation equips CD4+ T cells with new functions. However, the effect of cell differentiation on T cell receptor (TCR) repertoire is not investigated. Here, we examined the features of TCR beta (TCRB) repertoire of the top clones within naïve, memory and regular T cell (Treg) subsets: repertoire structure, gene usage, length distribution and sequence composition. First, we found that memory subsets and Treg would be discriminated from naïve by the features of TCRB repertoire. Second, we found that the correlations between the features of memory subsets and naïve were positively related to differentiation levels of memory subsets. Third, we found that public clones presented a reduced proportion and a skewed sequence composition in differentiated subsets. Furthermore, we found that public clones led naïve to recognize a broader spectrum of antigens than other subsets. Our findings suggest that TCRB repertoire of CD4+ T cell subsets is skewed in a differentiation-depended manner. Our findings show that the variations of public clones contribute to these changes. Our findings indicate that the reduce of public clones in differentiation trim the antigen specificity of CD4+ T cells. The study unveils the physiological effect of memory formation and facilitates the selection of proper CD4+ subset for cellular therapy. url: https://doi.org/10.1101/2020.11.01.364224 doi: 10.1101/2020.11.01.364224 id: cord-104001-5clslvqb author: Wang, Xiaoqi title: selfRL: Two-Level Self-Supervised Transformer Representation Learning for Link Prediction of Heterogeneous Biomedical Networks date: 2020-10-21 words: 5522.0 sentences: 292.0 pages: flesch: 49.0 cache: ./cache/cord-104001-5clslvqb.txt txt: ./txt/cord-104001-5clslvqb.txt summary: The meta path detection-based self-supervised learning task is proposed to learn representation vectors that can capture the global-level structure and semantic feature in HBNs. The vertex entity mask-based self-supervised learning mechanism is designed to enhance local association of vertices. First, a meta path detection self-supervised learning mechanism is developed to train a deep Transformer encoder for learning low-dimensional representations that capture the path-level information on HBNs. Meanwhile, sel-fRL integrates the vertex entity mask task to learn local association of vertices in HBNs. Finally, the representations from the entity mask and meta path detection is concatenated for generating the embedding vectors of nodes in HBNs. The results of link prediction on six datasets show that the proposed selfRL is superior to 25 state-of-the-art methods. • We proposed a two-level self-supervised representation learning method for HBNs, where this study integrates the meta path detection and vertex entity mask selfsupervised learning task based on a great number of unlabeled data to learn high quality representation vector of vertices. abstract: Predicting potential links in heterogeneous biomedical networks (HBNs) can greatly benefit various important biomedical problem. However, the self-supervised representation learning for link prediction in HBNs has been slightly explored in previous researches. Therefore, this study proposes a two-level self-supervised representation learning, namely selfRL, for link prediction in heterogeneous biomedical networks. The meta path detection-based self-supervised learning task is proposed to learn representation vectors that can capture the global-level structure and semantic feature in HBNs. The vertex entity mask-based self-supervised learning mechanism is designed to enhance local association of vertices. Finally, the representations from two tasks are concatenated to generate high-quality representation vectors. The results of link prediction on six datasets show selfRL outperforms 25 state-of-the-art methods. In particular, selfRL reveals great performance with results close to 1 in terms of AUC and AUPR on the NeoDTI-net dataset. In addition, the PubMed publications demonstrate that nine out of ten drugs screened by selfRL can inhibit the cytokine storm in COVID-19 patients. In summary, selfRL provides a general frame-work that develops self-supervised learning tasks with unlabeled data to obtain promising representations for improving link prediction. url: https://doi.org/10.1101/2020.10.20.347153 doi: 10.1101/2020.10.20.347153 id: cord-103618-cl7evbr3 author: Wang, Yingxue title: The WD and linker domains of ATG16L1 required for non-canonical autophagy limit lethal respiratory infection by influenza A virus at epithelial surfaces date: 2020-05-07 words: 5685.0 sentences: 324.0 pages: flesch: 51.0 cache: ./cache/cord-103618-cl7evbr3.txt txt: ./txt/cord-103618-cl7evbr3.txt summary: Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high Introduction Influenza A virus (IAV) is a respiratory pathogen of major global public health concern (Yamayoshi & Kawaoka, 2019). These mice, which lack non-canonical autophagy in phagocytic cells ( δWD mice infected with IAV appeared to be unable to resolve inflammatory responses resulting in sustained expression of pro-inflammatory cytokines, morbidity and 10 a striking lung pathology characterized by profuse migration of neutrophils into the airway at day 3 followed by macrophages on day 7. abstract: Respiratory viruses such as influenza A virus (IAV) and SARS-CoV-2 (Covid-19) cause pandemic infections where cytokine storm syndrome, lung inflammation and pneumonia lead to high mortality. Given the high social and economic cost of these viruses, there is an urgent need for a comprehensive understanding of how the airways defend against virus infection. Viruses entering cells by endocytosis are killed when delivered to lysosomes for degradation. Lysosome delivery is facilitated by non-canonical autophagy pathways that conjugate LC3 to endo-lysosome compartments to enhance lysosome fusion. Here we use mice lacking the WD and linker domains of ATG16L1 to demonstrate that non-canonical autophagy protects mice from lethal IAV infection of the airways. Mice with systemic loss of non-canonical autophagy are exquisitely sensitive to low-pathogenicity murine-adapted IAV where extensive viral replication throughout the lungs, coupled with cytokine amplification mediated by plasmacytoid dendritic cells, leads to fulminant pneumonia, lung inflammation and high mortality. IAV infection was controlled within epithelial barriers where non-canonical autophagy slowed fusion of IAV with endosomes and reduced activation of interferon signalling. This was consistent with conditional mouse models and ex vivo analysis showing that protection against IAV infection of lung was independent of phagocytes and other leukocytes. This establishes non-canonical autophagy pathways in airway epithelial cells as a novel innate defence mechanism that can restrict IAV infection and lethal inflammation at respiratory surfaces. url: https://doi.org/10.1101/2020.01.15.907873 doi: 10.1101/2020.01.15.907873 id: cord-104073-vsa5y7ip author: Warner, Emily F. title: Cross kingdom analysis of putative quadruplex-forming sequences in fungal genomes: novel antifungal targets to ameliorate fungal pathogenicity? date: 2020-09-23 words: 3218.0 sentences: 207.0 pages: flesch: 54.0 cache: ./cache/cord-104073-vsa5y7ip.txt txt: ./txt/cord-104073-vsa5y7ip.txt summary: PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. Using a computational approach, we identified putative quadruplex-forming 30 sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential 31 involvement in virulence, drug resistance, and pathogenicity. PQS in the 35 clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida 36 albicans were located within genes (particularly coding regions), mRNA, repeat regions, 37 abstract: Fungi contribute to upwards of 1.5 million human deaths annually, are involved in the spoilage of up to a third of food crops, and have a devastating effect on plant and animal biodiversity. Moreover, this already significant issue is exacerbated by a rise in antifungal resistance and a critical requirement for novel drug targets. Quadruplexes are four-stranded secondary structures in nucleic acids which can regulate processes such as transcription, translation, replication, and recombination. They are also found in genes linked to virulence in microbes, and quadruplex-binding ligands have been demonstrated to eliminate drug resistant pathogens. Using a computational approach, we identified putative quadruplex-forming sequences (PQS) in 1362 genomes across the fungal kingdom and explored their potential involvement in virulence, drug resistance, and pathogenicity. Here we present the largest analysis of PQS in fungi and identified significant heterogeneity of these sequences throughout phyla, genera, and species. Moreover, PQS were genetically conserved. Notably, loss of PQS in cryptococci and aspergilli was associated with pathogenicity. PQS in the clinically important pathogens Aspergillus fumigatus, Cryptococcus neoformans, and Candida albicans were located within genes (particularly coding regions), mRNA, repeat regions, mobile elements, tRNA, ncRNA, rRNA, and the centromere. Genes containing PQS in these organisms were found to be primarily associated with metabolism, nucleic acid binding, transporter activity, and protein modification. Finally, PQS were found in over 100 genes associated with virulence, drug resistance, or key biological processes in these pathogenic fungi and were found in genes which were highly upregulated during germination, hypoxia, oxidative stress, iron limitation, and in biofilms. Taken together, quadruplexes in fungi could present interesting novel targets to ameliorate fungal virulence and overcome drug resistance. url: https://doi.org/10.1101/2020.09.23.310581 doi: 10.1101/2020.09.23.310581 id: cord-103876-2rg2qtdq author: Watkins, Laura C. title: Influenza A M2 Inhibitor Binding Understood through Mechanisms of Excess Proton Stabilization and Channel Dynamics date: 2020-06-20 words: 5528.0 sentences: 249.0 pages: flesch: 47.0 cache: ./cache/cord-103876-2rg2qtdq.txt txt: ./txt/cord-103876-2rg2qtdq.txt summary: In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. Along with an earlier qualitative MD simulation study that guided the design of the spiro-adamantyl amine inhibitors, 41 the crystallographic analysis provided potential insights into the mechanism of inhibition, suggesting that the backbone carbonyls of pore-lining residues act as physiochemical chameleons, able to engage in both hydrophobic and hydrophilic interactions, and that the drug is tilted off the channel''s axis and interacts with waters in the Ala30 layer. Most recently, we further analyzed the MS-RMD simulations to explore the detailed interactions between the hydrated excess proton and the channel and found that the proton dynamically, as a function of its position, alters several properties of the protein and pore waters, including the hydrogen-bonding network and the protein structure. abstract: Prevalent resistance to inhibitors that target the influenza A M2 proton channel has necessitated a continued drug design effort, supported by a sustained study of the mechanism of channel function and inhibition. Recent high-resolution X-ray crystal structures present the first opportunity to see how the adamantyl-amine class of inhibitors bind to M2 and disrupt and interact with the channel’s water network, providing insight into the critical properties that enable their effective inhibition in wildtype M2. In this work, we test the hypothesis that these drugs act primarily as mechanism-based inhibitors by comparing hydrated excess proton stabilization during proton transport in M2 with the interactions revealed in the crystal structures, using the Multiscale Reactive Molecular Dynamics (MS-RMD) methodology. MS-RMD, unlike classical molecular dynamics, models the hydrated proton (hydronium-like cation) as a dynamic excess charge defect and allows bonds to break and form, capturing the intricate interactions between the hydrated excess proton, protein atoms, and water. Through this, we show that the ammonium group of the inhibitors is effectively positioned to take advantage of the channel’s natural ability to stabilize an excess protonic charge and is thus acting as a hydronium-mimic. Additionally, we show that the channel is especially stable in the drug binding region, highlighting the importance of this property for binding the adamantane group. Finally, we characterize an additional hinge point near Val27, which dynamically responds to charge and inhibitor binding. Altogether, this work further illuminates a dynamic understanding of the mechanism of drug inhibition in M2, grounded in the fundamental properties that enable the channel to transport and stabilize excess protons, with critical implications for future drug design efforts. TOC Graphic url: https://doi.org/10.1101/2020.06.19.162248 doi: 10.1101/2020.06.19.162248 id: cord-103853-ar09nzmw author: Wayment-Steele, Hannah K. title: RNA secondary structure packages ranked and improved by high-throughput experiments date: 2020-05-31 words: 4328.0 sentences: 201.0 pages: flesch: 42.0 cache: ./cache/cord-103853-ar09nzmw.txt txt: ./txt/cord-103853-ar09nzmw.txt summary: 20 In this work, we evaluate the performance of commonly-used packages capable of making thermodynamic predictions in two tasks that have been crowdsourced on Eterna and are emerging as central to RNA characterization and design: 1) predicting chemical reactivity data through calculating probabilities that nucleotides are unpaired, and 2) predicting relative stabilities of multiple structural states that underlie the functions of riboswitch molecules, a task that involves predicting affinities of both small molecules and proteins of interest. We evaluated commonly used secondary structure modeling packages in their ability to make thermodynamic predictions on a compilation of large datasets of diverse synthetic molecules from Eterna, which we termed EternaBench ( Figure 1A ). We trained models with a variety of combinations of data types to explore interactions in multitask training (Table 1) and evaluated performance on held-out test sets for single-structure prediction accuracy, chemical mapping prediction accuracy, and riboswitch fold change prediction. abstract: The computer-aided study and design of RNA molecules is increasingly prevalent across a range of disciplines, yet little is known about the accuracy of commonly used structure prediction packages in real-world tasks. Here, we evaluate the performance of current packages using EternaBench, a dataset comprising 23 in vitro structure mapping and 11 riboswitch activity datasets involving 18,509 synthetic sequences from the crowdsourced RNA design project Eterna. We find that CONTRAfold and RNAsoft, packages with parameters derived through statistical learning, achieve consistently higher accuracy than more widely used packages like the ViennaRNA software, which derive parameters primarily from thermodynamic experiments. Motivated by these results, we develop a multitask-learning-based model, EternaFold, which demonstrates improved performance that generalizes to diverse external datasets, including complete viral genomes probed in vivo and synthetic designs modeling mRNA vaccines. url: https://doi.org/10.1101/2020.05.29.124511 doi: 10.1101/2020.05.29.124511 id: cord-327520-qj7coqfr author: Wei, Yulong title: Coronavirus genomes carry the signatures of their habitats date: 2020-06-13 words: 1395.0 sentences: 93.0 pages: flesch: 54.0 cache: ./cache/cord-327520-qj7coqfr.txt txt: ./txt/cord-327520-qj7coqfr.txt summary: Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Here we compared the CpG and U content 327 of these coronaviruses and found that viruses that regularly infect AVP-rich tissues tend to Based on global sequence comparison, figure 4a shows that most SNPs are C->U substitutions. abstract: Coronaviruses such as SARS-CoV-2 regularly infect host tissues that express antiviral proteins (AVPs) in abundance. Understanding how they evolve to adapt or evade host immune responses is important in the effort to control the spread of COVID-19. Two AVPs that may shape viral genomes are the zinc finger antiviral protein (ZAP) and the apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3 protein (APOBEC3). The former binds to CpG dinucleotides to facilitate the degradation of viral transcripts while the latter deaminates C into U residues leading to dysfunctional transcripts. We tested the hypothesis that both APOBEC3 and ZAP may act as primary selective pressures that shape the genome of an infecting coronavirus by considering a comprehensive number of publicly available genomes for seven coronaviruses (SARS-CoV-2, SARS-CoV, MERS, Bovine CoV, Murine MHV, Porcine HEV, and Canine CoV). We show that coronaviruses that regularly infect tissues with abundant AVPs have CpG-deficient and U-rich genomes; whereas viruses that do not infect tissues with abundant AVPs do not share these sequence hallmarks. In SARS-CoV-2, CpG is most deficient in the S protein region to evaded ZAP-mediated antiviral defense during cell entry. Furthermore, over four months of SARS-CoV-2 evolutionary history, we observed a marked increase in C to U substitutions in the 5’ UTR and ORF1ab regions. This suggests that the two regions could be under constant C to U deamination by APOBEC3. The evolutionary pressures exerted by host immune systems onto viral genomes may motivate novel strategies for SARS-CoV-2 vaccine development. url: https://doi.org/10.1101/2020.06.13.149591 doi: 10.1101/2020.06.13.149591 id: cord-314329-rzda8x62 author: Wells, Stephen A. title: Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure date: 2020-03-12 words: 4108.0 sentences: 208.0 pages: flesch: 50.0 cache: ./cache/cord-314329-rzda8x62.txt txt: ./txt/cord-314329-rzda8x62.txt summary: A judicious combination of simplified methodologiesrigidity analysis, elastic network modelling, and geometric simulation of flexible motioncan work together to extract valuable information on the large-amplitude, low-frequency motions of a protein structure, at a fraction of the computational cost (in resources and time) of molecular dynamics (MD) approaches [3] . The simulations reported here suggest that the protease structure is capable of substantial flexible motions which alter domain orientations, open and close clefts, and affect the geometry of an inhibitor-binding site. The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. abstract: The rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. This computational investigation of the viral protease follows protocols that have been effective in studying other homodimeric enzymes. The protease is predicted to display flexible motions in vivo which directly affect the geometry of a known inhibitor binding site and which open new potential binding sites elsewhere in the structure. A database of generated PDB files representing natural flexible variations on the crystal structures has been produced and made available for download from an institutional data archive. This information may inform structure-based drug design and fragment screening efforts aimed at identifying specific antiviral therapies for the treatment of COVID-19. url: https://doi.org/10.1101/2020.03.10.986190 doi: 10.1101/2020.03.10.986190 id: cord-103029-nc5yf6x4 author: Wichmann, Stefan title: Computational design of genes encoding completely overlapping protein domains: Influence of genetic code and taxonomic rank date: 2020-09-25 words: 8665.0 sentences: 387.0 pages: flesch: 52.0 cache: ./cache/cord-103029-nc5yf6x4.txt txt: ./txt/cord-103029-nc5yf6x4.txt summary: In this study the artificially designed sequences are compared to their original sequences in terms of amino acid identity, amino acid similarity, Hidden Markov Model profile and secondary structure in order to determine the impact of OLG construction and which sequences are potentially functional. While the previous study [30] tried to estimate an upper limit of how many domains can be successfully overlapped in at least one reading frame and position, here the average success rate for OLG construction is determined instead, which is more relevant in relation to both understanding constraints on the formation rate of naturally occuring OLGs and in assessing the likelihood of successful synthetic creation of OLGs. These results in one sense give an upper estimate of the ease of creating overlaps as the difficulty of obtaining an overlapping gene pair naturally is not directly addressed here. abstract: Overlapping genes (OLGs) with long protein-coding overlapping sequences are often excluded by genome annotation programs, with the exception of virus genomes. A recent study used a novel algorithm to construct OLGs from arbitrary protein domain pairs and concluded that virus genes are best suited for creating OLGs, a result which fitted with common assumptions. However, improving sequence evaluation using Hidden Markov Models shows that the previous result is an artifact originating from dataset-database biases. When parameters for OLG design and evaluation are optimized we find that 94.5% of the constructed OLG pairs score at least as highly as naturally occurring sequences, while 9.6% of the artificial OLGs cannot be distinguished from typical sequences in their protein family. Constructed OLG sequences are also indistinguishable from natural sequences in terms of amino acid identity and secondary structure, while the minimum nucleotide change required for overprinting an overlapping sequence can be as low as 1.8% of the sequence. Separate analysis of datasets containing only sequences from either archaea, bacteria, eukaryotes or viruses showed that, surprisingly, virus genes are much less suitable for designing OLGs than bacterial or eukaryotic genes. An important factor influencing OLG design is the structure of the standard genetic code. Success rates in different reading frames strongly correlate with their code-determined respective amino acid constraints. There is a tendency indicating that the structure of the standard genetic code could be optimized in its ability to create OLGs while conserving mutational robustness. The findings reported here add to the growing evidence that OLGs should no longer be excluded in prokaryotic genome annotations. Determining the factors facilitating the computational design of artificial overlapping genes may improve our understanding of the origin of these remarkable genetic constructs and may also open up exciting possibilities for synthetic biology. url: https://doi.org/10.1101/2020.09.25.312959 doi: 10.1101/2020.09.25.312959 id: cord-103297-4stnx8dw author: Widrich, Michael title: Modern Hopfield Networks and Attention for Immune Repertoire Classification date: 2020-08-17 words: 14093.0 sentences: 926.0 pages: flesch: 57.0 cache: ./cache/cord-103297-4stnx8dw.txt txt: ./txt/cord-103297-4stnx8dw.txt summary: In this work, we present our novel method DeepRC that integrates transformer-like attention, or equivalently modern Hopfield networks, into deep learning architectures for massive MIL such as immune repertoire classification. DeepRC sets out to avoid the above-mentioned constraints of current methods by (a) applying transformer-like attention-pooling instead of max-pooling and learning a classifier on the repertoire rather than on the sequence-representation, (b) pooling learned representations rather than predictions, and (c) using less rigid feature extractors, such as 1D convolutions or LSTMs. In this work, we contribute the following: We demonstrate that continuous generalizations of binary modern Hopfield-networks (Krotov & Hopfield, 2016 Demircigil et al., 2017) have an update rule that is known as the attention mechanisms in the transformer. We evaluate the predictive performance of DeepRC and other machine learning approaches for the classification of immune repertoires in a large comparative study (Section "Experimental Results") Exponential storage capacity of continuous state modern Hopfield networks with transformer attention as update rule abstract: A central mechanism in machine learning is to identify, store, and recognize patterns. How to learn, access, and retrieve such patterns is crucial in Hopfield networks and the more recent transformer architectures. We show that the attention mechanism of transformer architectures is actually the update rule of modern Hop-field networks that can store exponentially many patterns. We exploit this high storage capacity of modern Hopfield networks to solve a challenging multiple instance learning (MIL) problem in computational biology: immune repertoire classification. Accurate and interpretable machine learning methods solving this problem could pave the way towards new vaccines and therapies, which is currently a very relevant research topic intensified by the COVID-19 crisis. Immune repertoire classification based on the vast number of immunosequences of an individual is a MIL problem with an unprecedentedly massive number of instances, two orders of magnitude larger than currently considered problems, and with an extremely low witness rate. In this work, we present our novel method DeepRC that integrates transformer-like attention, or equivalently modern Hopfield networks, into deep learning architectures for massive MIL such as immune repertoire classification. We demonstrate that DeepRC outperforms all other methods with respect to predictive performance on large-scale experiments, including simulated and real-world virus infection data, and enables the extraction of sequence motifs that are connected to a given disease class. Source code and datasets: https://github.com/ml-jku/DeepRC url: https://doi.org/10.1101/2020.04.12.038158 doi: 10.1101/2020.04.12.038158 id: cord-264031-0y7xbgun author: Wierbowski, Shayne D. title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions date: 2020-10-13 words: 5066.0 sentences: 291.0 pages: flesch: 42.0 cache: ./cache/cord-264031-0y7xbgun.txt txt: ./txt/cord-264031-0y7xbgun.txt summary: title: A 3D Structural Interactome to Explore the Impact of Evolutionary Divergence, Population Variation, and Small-molecule Drugs on SARS-CoV-2-Human Protein-Protein Interactions This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. Further, we explore the utility of our interactome modeling approach in identifying key 99 interactions undergoing evolution along viral protein interfaces, highlighting population variants on 100 human interfaces that could modulate the strength of viral-host interactions to confer protection from or 101 susceptibility to COVID-19, and prioritizing drug candidates predicted to bind competitively at viral-102 human interaction interfaces. abstract: The recent COVID-19 pandemic has sparked a global public health crisis. Vital to the development of informed treatments for this disease is a comprehensive understanding of the molecular interactions involved in disease pathology. One lens through which we can better understand this pathology is through the network of protein-protein interactions between its viral agent, SARS-CoV-2, and its human host. For instance, increased infectivity of SARS-CoV-2 compared to SARS-CoV can be explained by rapid evolution along the interface between the Spike protein and its human receptor (ACE2) leading to increased binding affinity. Sequence divergences that modulate other protein-protein interactions may further explain differences in transmission and virulence in this novel coronavirus. To facilitate these comparisons, we combined homology-based structural modeling with the ECLAIR pipeline for interface prediction at residue resolution, and molecular docking with PyRosetta. This enabled us to compile a novel 3D structural interactome meta-analysis for the published interactome network between SARS-CoV-2 and human. This resource includes docked structures for all interactions with protein structures, enrichment analysis of variation along interfaces, predicted ΔΔG between SARS-CoV and SARS-CoV-2 variants for each interaction, predicted impact of natural human population variation on binding affinity, and a further prioritized set of drug repurposing candidates predicted to overlap with protein interfaces†. All predictions are available online† for easy access and are continually updated when new interactions are published. † Some sections of this pre-print have been redacted to comply with current bioRxiv policy restricting the dissemination of purely in silico results predicting potential therapies for SARS-CoV-2 that have not undergone thorough peer-review. The results section titled “Prioritization of Candidate Inhibitors of SARS-CoV-2-Human Interactions Through Binding Site Comparison,” Figure 4, Supplemental Table 9, and all links to our web resource have been removed. Blank headers left in place to preserve structure and item numbering. Our full manuscript will be published in an appropriate journal following peer-review. url: https://doi.org/10.1101/2020.10.13.308676 doi: 10.1101/2020.10.13.308676 id: cord-291677-zcbyhsf1 author: Wilamowski, M. title: Methylation of RNA Cap in SARS-CoV-2 captured by serial crystallography date: 2020-08-16 words: 5348.0 sentences: 308.0 pages: flesch: 56.0 cache: ./cache/cord-291677-zcbyhsf1.txt txt: ./txt/cord-291677-zcbyhsf1.txt summary: To investigate the 2′-O methyltransferase activity of SARS-CoV-2 Nsp10/16, we applied fixed-target serial synchrotron crystallography (SSX) which allows for physiological temperature data collection from thousands of crystals, significantly reducing the x-ray dose while maintaining a biologically relevant temperature. We conducted serial synchrotron crystallography (SSX) experiments at 297 K to test whether low radiation dose could help uncover the structure of Nsp10/16 in a complex with Cap-1. The SARS-CoV-2 Nsp10/16 2′-O MTase complex provides a molecular arrangement for binding of the mRNA Cap-0 and subsequent methylation of the first transcribed nucleotide. The further development of SSX and implementation of time-resolved SSX crystallography is an approach that could visualize chemical processes and protein molecular dynamics -such as of the transfer of the methyl group catalyzed by Nsp10/16 2′O-MTase from SARS-CoV-2. Crystal structure and functional analysis of the SARS-coronavirus RNA cap 2′-o-methyltransferase nsp10/nsp16 complex abstract: The genome of the SARS-CoV-2 coronavirus contains 29 proteins, of which 15 are nonstructural. Nsp10 and Nsp16 form a complex responsible for the capping of mRNA at the 5′ terminus. In the methylation reaction the S-adenosyl-L-methionine serves as the donor of the methyl group that is transferred to Cap-0 at the first transcribed nucleotide to create Cap-1. The presence of Cap-1 makes viral RNAs mimic the host transcripts and prevents their degradation. To investigate the 2′-O methyltransferase activity of SARS-CoV-2 Nsp10/16, we applied fixed-target serial synchrotron crystallography (SSX) which allows for physiological temperature data collection from thousands of crystals, significantly reducing the x-ray dose while maintaining a biologically relevant temperature. We determined crystal structures of Nsp10/16 that revealed the states before and after the methylation reaction, for the first time illustrating coronavirus Nsp10/16 complexes with the m7GpppAm2′-O Cap-1, where 2′OH of ribose is methylated. We compare these structures with structures of Nsp10/16 at 297 K and 100 K collected from a single crystal. This data provide important mechanistic insight and can be used to design small molecules that inhibit viral RNA maturation making SARS-CoV-2 sensitive to host innate response. url: https://doi.org/10.1101/2020.08.14.251421 doi: 10.1101/2020.08.14.251421 id: cord-102634-0n42h72w author: Willforss, Jakob title: OmicLoupe: Facilitating biological discovery by interactive exploration of multiple omic datasets and statistical comparisons date: 2020-10-22 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Visual exploration of gene product behavior across multiple omic datasets can pinpoint technical limitations in data and reveal biological trends. The OmicLoupe software was developed to facilitate such exploration and provides more than 15 interactive cross-dataset visualizations for omic data. It expands visualizations to multiple datasets for quality control, statistical comparisons and overlap and correlation analyses, while allowing for rapid inspection and downloading of selected features. The usage of OmicLoupe is demonstrated in three diverse studies, including an analysis of SARS-CoV-2 infection across omic layers, based on previously published proteomics and transcriptomics studies. OmicLoupe is available at quantitativeproteomics.org/omicloupe url: https://doi.org/10.1101/2020.10.22.349944 doi: 10.1101/2020.10.22.349944 id: cord-102145-bi8jyz6r author: Wilson, Audrey E title: Spatial heterogeneity in resources alters selective dynamics in Drosophila melanogaster date: 2020-09-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Environmental features can alter the behaviours and phenotypes of organisms and populations evolving within them including the dynamics between natural and sexual selection. Experimental environmental manipulation, particularly when conducted in experiments where the dynamics of the purging of deleterious alleles are compared, has demonstrated both direct and indirect effects on the strength and direction of selection. However, many of these experiments are conducted with fairly simplistic environments when it is not always clear how or why particular forms of spatial heterogeneity may influence behaviour or selection. Using Drosophila melanogaster, we tested three different spatial environments designed to determine if spatial constraint of critical resources influences the efficiency of natural and sexual selection. We conducted two allele purging experiments to 1) assess the effects of these spatial treatments on the selective dynamics of six recessive mutations, and 2) determine how these dynamics changed when sexual selection was relaxed and the spatial area was reduced. We found that allele purging dynamics depended on spatial environment, however the patterns of purging rates between the environments differed across distinct deleterious mutations. We also found that for two of the mutations, the addition of sexual selection increased the purging rate. url: https://doi.org/10.1101/2020.09.05.283705 doi: 10.1101/2020.09.05.283705 id: cord-289367-zna8qkkv author: Wirden, Marc title: Multicenter comparison of the Cobas 6800 system with the RealStar RT-PCR kit for the detection of SARS-CoV-2 date: 2020-06-30 words: 1193.0 sentences: 72.0 pages: flesch: 61.0 cache: ./cache/cord-289367-zna8qkkv.txt txt: ./txt/cord-289367-zna8qkkv.txt summary: Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct. Conclusions In this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Then, each laboratory selected 45 to 49 samples firstly detected 88 using the Cobas 6800 with a stratification according to the Ct of the E gene Cobas results, 89 allowing to cover the whole linear range of the assays. This 207 is a limitation of our study as we did not assessed comparatively the limit of detection of the 208 two methods but the reliability of their Ct values among COBAS 6800 positive samples, 209 excluding those that could be negative with COBAS 6800 and positive with RealStar in this 210 range of low viral loads. RT-PCR assay for the detection of the emerging coronavirus SARS-CoV-2 using a high 278 throughput system abstract: Background RT-PCR testing is crucial in the diagnostic of SARS-CoV-2 infection. The use of reliable and comparable PCR assays is a cornerstone to allow use of different PCR assays depending on the local equipment. In this work, we provide a comparison of the Cobas® (Roche) and the RealStar® assay (Altona). Methods Assessment of the two assays was performed prospectively in three reference Parisians hospitals, using 170 clinical samples. They were tested with the Cobas® assay, selected to obtain a distribution of cycle threshold (Ct) as large as possible, and tested with the RealStar assay with three largely available extraction platforms: QIAsymphony (Qiagen), MagNAPure (Roche) and NucliSENS-easyMag (BioMérieux). Results Overall, the agreement (positive for at least one gene) was 76%. This rate differed considerably depending on the Cobas Ct values for gene E: below 35 (n = 91), the concordance was 99%. Regarding the positive Ct values, linear regression analysis showed a determination correlation (R2) of 0.88 and the Deming regression line revealed a strong correlation with a slope of 1.023 and an intercept of -3.9. Bland-Altman analysis showed that the mean difference (Cobas® minus RealStar®) was + 3.3 Ct, with a SD of + 2.3 Ct. Conclusions In this comparison, both RealStar® and Cobas® assays provided comparable qualitative results and a high correlation when both tests were positive. Discrepancies exist after 35 Ct and varied depending on the extraction system used for the RealStar® assay, probably due to a low viral load close to the detection limit of both assays. url: https://doi.org/10.1101/2020.06.29.179184 doi: 10.1101/2020.06.29.179184 id: cord-306924-dw35dlx3 author: Wohlers, Inken title: COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans date: 2020-11-03 words: 798.0 sentences: 59.0 pages: flesch: 54.0 cache: ./cache/cord-306924-dw35dlx3.txt txt: ./txt/cord-306924-dw35dlx3.txt summary: title: COVID-19 risk haplogroups differ between populations, deviate from Neanderthal haplotypes and compromise risk assessment in non-Europeans Recent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. We show that (i) COVID-19-related genetic factors of Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic. However, as two positions carry protective alleles the risk probability of the 51 previously assessed Vindija Neanderthal haplotype is only 52%. 82 83 All human risk haplogroups differ from Neanderthal haplotypes (Fig. 1c) If this variant was causal (2% probability) using lead variants such as rs11385942 or 120 rs35044562 would incorrectly classify individuals carrying these haplogroups to be at 121 risk. The major genetic risk factor for severe COVID-19 is 142 inherited from Neanderthals abstract: Recent genome wide association studies (GWAS) have identified genetic risk factors for developing severe COVID-19 symptoms. The studies reported a 1bp insertion rs11385942 on chromosome 31 and furthermore two single nucleotide variants (SNVs) rs35044562 and rs679599192, all three correlated with each other. Zeberg and Pääbo3 subsequently traced them back to Neanderthal origin. They found that a 49.4 kb genomic region including the risk allele of rs35044562 is inherited from Neanderthals of Vindija in Croatia. Here we add a differently focused evaluation of this major genetic risk factor to these recent analyses. We show that (i) COVID-19-related genetic factors of Neanderthals deviate from those of modern humans and that (ii) they differ among world-wide human populations, which compromises risk prediction in non-Europeans. Currently, caution is thus advised in the genetic risk assessment of non-Europeans during this world-wide COVID-19 pandemic. url: https://doi.org/10.1101/2020.11.02.365551 doi: 10.1101/2020.11.02.365551 id: cord-103509-hynnba03 author: Wong, Ten-Tsao title: A self-assembled protein nanoparticle serving as a one-shot vaccine carrier date: 2020-09-18 words: 3187.0 sentences: 148.0 pages: flesch: 48.0 cache: ./cache/cord-103509-hynnba03.txt txt: ./txt/cord-103509-hynnba03.txt summary: From these two clues, it was hypothesized that AH3-GFP fusion protein form stable protein complex through hydrophobic interaction mediated by N-terminal AH3 peptide. Using the same protocol, AH3-GFP was found to co-sedimented with the bacterial membrane (Fig. S3A) as well as the AH3-sfGFP-hM2e fusion protein but not a free GFP protein (Fig S3B) These results are consistent with our protein structure modeling that Arg11 serves as a main contact point for dimer stacking also it mediates the electrostatic interaction with mutated Glu13 (Fig. 3E ). These results suggest that the two point mutations of AH3 in I8L and K13E enable the formation of a stable, high antigenic protein complex that stimulates long lasting immune responses in a single immunization. The result suggests that although carrier protein AH3-sfGFP also has high antigenicity, it did not interfere with the immune response against the heterologous protein, hM2e (Fig. 5B, 5C) abstract: In this paper, we are exploring the role of an amphipathic helical peptide in mediating the self-assembly of a fusion protein into a protein nanoparticle and the application of the nanoparticle as a one-shot vaccine carrier. Out of several candidates, an amphipathic helical peptide derived from M2 protein of type A influenza virus is found to stimulate high antigenicity when fused to a fluorescent protein genetically. This fusion protein was found to form protein nanoparticle spontaneously when expressed and purified protein stimulates long-lasting antibody responses in single immunization. Through modeling peptide structure and nanoparticle assembly, we have improved this vaccine carrier in complex stability. The revised vaccine carrier is able to stimulate constant antibody titer to a heterologous antigen for at least six months in single immunization. The immune response against a heterologous antigen can be boosted further by additional immunization in spite of high immune responses to carrier protein. url: https://doi.org/10.1101/2020.09.16.299149 doi: 10.1101/2020.09.16.299149 id: cord-102891-0z397ppn author: Wren, Brandi title: Social contact behaviors are associated with infection status for whipworm (Trichuris sp.) in wild vervet monkeys (Chlorocebus pygerythrus) date: 2020-10-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Social grooming in the animal kingdom is common and serves several functions, from removing ectoparasites to maintaining social bonds between conspecifics. We examined whether time spent grooming with others in a highly social mammal species was associated with infection status for gastrointestinal parasites. Of six parasites detected, one (Trichuris sp.) was associated with social grooming behaviors, but more specifically with direct physical contact with others. Individuals infected with Trichuris sp. spent significantly less time grooming conspecifics than those not infected, and time in direct contact with others was the major predictor of infection status. One model correctly predicted infection status for Trichuris sp. with a reliability of 95.17% overall when the variables used were time spent in direct contact and time spent grooming others. This decrease in time spent grooming and interacting with others is likely a sickness behavior displayed by individuals with less energy or motivation for non-essential behaviors. This study highlights the need for an understanding of a study population’s parasitic infections when attempting to interpret animal behavior. url: https://doi.org/10.1101/2020.10.07.329409 doi: 10.1101/2020.10.07.329409 id: cord-103041-ymr3e60k author: Wu, Yue title: Homeostatic mechanisms regulate distinct aspects of cortical circuit dynamics date: 2019-10-02 words: 7957.0 sentences: 423.0 pages: flesch: 42.0 cache: ./cache/cord-103041-ymr3e60k.txt txt: ./txt/cord-103041-ymr3e60k.txt summary: To understand how neural circuits exploit various synaptic plasticity and homeostatic mechanisms to decrease and recover both firing rates and correlations during MD, we built a plastic recurrent network model consisting of randomly connected excitatory and inhibitory spiking neurons (Methods). Based on these experimental findings, besides Hebbian plasticity during training, we modeled these two distinct homeostatic mechanisms following MD: (1) synaptic scaling which acts only on excitatory synapses (Turrigiano et al., 1998; Hengen et al., 2013) , and (2) intrinsic plasticity which modifies the intrinsic excitability of both excitatory and inhibitory neurons (Grubb and Burrone, 2010; Campanac et al., 2013) (Methods) . We speculated that this failure to recover correlations in the model network, despite the recovery of firing rates, could be the result of perturbing the structured connectivity between excitatory neurons within assemblies generated through training (Fig. 3B) . abstract: Homeostasis is indispensable to counteract the destabilizing effects of Hebbian plasticity. Although it is commonly assumed that homeostasis modulates synaptic strength, membrane excitability and firing rates, its role at the neural circuit and network level is unknown. Here, we identify changes in higher-order network properties of freely behaving rodents during prolonged visual deprivation. Strikingly, our data reveal that pairwise functional correlations and their structure are subject to homeostatic regulation. Using a computational model, we demonstrate that the interplay of different plasticity and homeostatic mechanisms can capture the initial drop and delayed recovery of firing rates and correlations observed experimentally. Moreover, our model indicates that synaptic scaling is crucial for the recovery of correlations and network structure, while intrinsic plasticity is essential for the rebound of firing rates, suggesting that synaptic scaling and intrinsic plasticity can serve distinct functions in homeostatically regulating network dynamics. url: https://doi.org/10.1101/790410 doi: 10.1101/790410 id: cord-102842-51n5mnjb author: Węglarz-Tomczak, Ewelina title: Ebselen as a highly active inhibitor of PLProCoV2 date: 2020-05-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Since December 2019 a novel a coronavirus identified as SARS-CoV-2 or COV2 has been spreading around the world. On the 16th of May around 4.5 million people got infected and over 300,000 died due to the infection of COV2. The effective treatment remains a challenge. Targeted therapeutics are still under investigation. The papain-like protease (PLPro) from the human SARS-CoV-2 coronavirus is a cysteine protease that plays a critical role in virus replication. Its activity is required to process the viral polyprotein into functional, mature subunits. Moreover, COV2 uses this enzyme to modulate the host’s immune system to its own benefit. Therefore, it represents a highly promising target for the development of antiviral drugs. In this work, we discovered that ebselen, a synthetic organoselenium drug molecule with anti-inflammatory, anti-oxidant and cytoprotective activity in mammalian cells and cytotoxicity in lower organisms, is a highly active inhibitor of PLProCoV2. We proved that ebselen is a covalent, fast-binding inhibitor of PLProCoV2 exhibiting a low micromolar potency. Furthermore, we identified a difference between PLPro from SARS-CoV-1 (the corona virus which caused the 2002–2004 outbreak, SARS) and SARS-CoV-2 that allows to explain the difference in dynamics of the replication, and, thus, the disease progression. Namely, we present that they show differences in the binding affinity of substrates that we observed through kinetics and molecular docking studies. Using a novel Approximate Bayesian Computation method we were able to find kinetic constants for both enzymes. Molecular modeling study on the structure of the active site and binding mode of the ebselen with SARS and COV2 showed also significant differences that could explain our observation that ebselen is less active and slower bounding with SARS than COV2. In conclusion, we show that ebselen inhibits the activity of the essential viral enzyme papain-like protease (PLpro) from SARS-COV-2 in low micromolar range. url: https://doi.org/10.1101/2020.05.17.100768 doi: 10.1101/2020.05.17.100768 id: cord-355811-aq7p1uxo author: Węglarz-Tomczak, Ewelina title: Discovery of potent inhibitors of PLproCoV2 by screening a library of selenium-containing compounds date: 2020-05-21 words: 2008.0 sentences: 151.0 pages: flesch: 57.0 cache: ./cache/cord-355811-aq7p1uxo.txt txt: ./txt/cord-355811-aq7p1uxo.txt summary: A collection of twelve organoselenium compounds, structural analogues of antioxidant drug ebselen were screened for inhibition of the papain-like protease (PLpro) from the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, CoV2). In recent studies, peptide analogues [11] and ebselen [12] have been identified as highly active inhibitors for PL pro . We show that some of them indeed possess higher activity than ebselen, that has been recently reported as PL pro CoV2 inhibitor [12] , and, thus, could be considered as novel potential drugs against COVID-19. In this work, we used the ebselen derivatives/analogues library and performed a comprehensive inhibition study of PL pro CoV2. In the case of PL pro SARS, none of the presented ebselen derivatives was able to block the enzyme. Activity profiling and structures of inhibitor-bound SARS-CoV-2-PLpro protease provides a framework for anti-COVID-19 drug design Ebselen as a highly active inhibitor of PL pro CoV2 abstract: A collection of twelve organoselenium compounds, structural analogues of antioxidant drug ebselen were screened for inhibition of the papain-like protease (PLpro) from the acute respiratory syndrome coronavirus 2 (SARS-CoV-2, CoV2). This cysteine protease, being responsible for the hydrolysis of peptide bonds between specific amino acids, plays a critical role in CoV2 replication and in assembly of new viral particles within human cells. The activity of the PLpro CoV2 is essential for the progression of coronavirus disease 2019 (COVID-19) and it constitutes a key target for the development of anti-COVID-19 drugs. Here, we identified four strong inhibitors that bind favorably to the PLpro CoV2 with the IC50 in the nanomolar range. url: https://doi.org/10.1101/2020.05.20.107052 doi: 10.1101/2020.05.20.107052 id: cord-329118-0gq5yusk author: Xiang, Boyu title: ScRNA-seq discover cell cluster change under OAB: ACE2 expression reveal possible alternation of 2019-nCoV infectious pathway date: 2020-06-06 words: 1545.0 sentences: 83.0 pages: flesch: 55.0 cache: ./cache/cord-329118-0gq5yusk.txt txt: ./txt/cord-329118-0gq5yusk.txt summary: The purpose of our study is to explore cell cluster structure and ACE2 expression pattern in the bladder and use scRNA-seq to infer the effects of human senile lesions, OAB, on umbrella cells and intermediate cells in the bladder epithelium from the results of mice. Because this potential urinary tract infection pathway may be critical to prevent 2019n-Cov, here we used two scRNA-Seq transcriptomes to analyze bladder tissue from normal and OAB mice and combined human and mouse bladder ACE2 expression data from public data base to analyze the impact of underlying disease on this potential infectious system 7 . Single-cell Analysis of ACE2 Expression in Human Kidneys and Bladders Reveals a Potential Route of 2019-nCoV Infection abstract: Objective Previous study indicated that bladder cells which express ACE2 were a potential infection route of 2019-nCov. This study observed some differences of bladder cell cluster and their ACE2 expression between OAB mice and healthy mice, indicating the change of infectious possibility and pathway under overactive bladder (OAB) circumstance. Material and method Pubic dataset acquisition was used to get ACE2 expression in normal human bladder and mice bladder (GSE129845). We built up over OAB model and studied the impact on cell typing and ACE2 expression. By way of using single-cell RNA sequencing (scRNA-seq) technique, bladder cell clustering and ACE2 expression in various cell types were measured respectively. Result In pubic database (healthy human and mice bladder), ACE2 expression in humans and mice is concentrated in bladder epithelial cells. The disappearance of umbrella cells, a component of bladder epithelial, was found in our OAB model. In the two mouse bladder samples, ACE2 expression of epithelial cells is 34.1%, also the highest of all cell types. Conclusion The disappearance of umbrella cell may alternate the infection pathway of 2019-nCov and relate to the onset and progression of OAB. url: https://doi.org/10.1101/2020.06.05.137380 doi: 10.1101/2020.06.05.137380 id: cord-312228-wbyqmvhs author: Xiao, Minfeng title: Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples date: 2020-03-19 words: 3236.0 sentences: 194.0 pages: flesch: 56.0 cache: ./cache/cord-312228-wbyqmvhs.txt txt: ./txt/cord-312228-wbyqmvhs.txt summary: Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. 90 Therefore, we aim to comprehensively compare the sensitivity, inter-individual (variant) and 91 intra-individual (iSNV) accuracy, and other general features of different approaches by sys-92 tematically utilizing ultra-high-throughput metatranscriptomic, hybrid capture-based, and 93 amplicon-based sequencing approaches to obtain genomic information of HCoV-19 from 94 serial dilutions of a cultured isolate and directly from clinical samples. We assessed the correlations between the HCoV-19 genome copies per mL in diluted 396 samples of cultured isolates and the minimum amount of sequencing data for amplicon-397 and capture-based methods using Pearson correlation coefficient (R) with the function 398 scatter from the R package ggpubr (v3.6.1) 38 . abstract: COVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses. url: https://doi.org/10.1101/2020.03.16.993584 doi: 10.1101/2020.03.16.993584 id: cord-325420-e9fjo7tl author: Xiao, Xia title: Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2 date: 2020-07-06 words: 1282.0 sentences: 78.0 pages: flesch: 58.0 cache: ./cache/cord-325420-e9fjo7tl.txt txt: ./txt/cord-325420-e9fjo7tl.txt summary: Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Positive compounds from the initial screen were tested for their antiviral 120 efficacy against SARS-CoV-2 in Vero cells. Our data show that 24 of these compounds show significant 124 efficacy in inhibiting SARS-CoV-2 replication with sub micromolar IC50 for many of these 125 drugs such as nilotinib, clofazimine and raloxifene. This screen identified five new compounds that 187 are highly efficacious in inhibiting the viral replication of SARS-CoV-2 with SI >600. The positively identified drugs from this screen were used to perform dose response curves 220 against OC43 on LLC-MK2 and against SARS-CoV-2 using Vero cells as described below. abstract: COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic. url: https://doi.org/10.1101/2020.07.06.188953 doi: 10.1101/2020.07.06.188953 id: cord-337701-56tmg38b author: Xiao, Yan title: Comparison of three TaqMan Real-Time Reverse Transcription-PCR assays in detecting SARS-CoV-2 date: 2020-07-06 words: 2122.0 sentences: 120.0 pages: flesch: 57.0 cache: ./cache/cord-337701-56tmg38b.txt txt: ./txt/cord-337701-56tmg38b.txt summary: In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). No effect of the 152 co-existed other viral nucleic acids on the LOD and the linear detection range was 153 observed, although higher Ct values were generated than those of RNA transcript 154 alone as template in all of the three qRT-PCR assays. Although most of the evaluated 232 assays exhibited good sensitivity, specificity, reproducibility and wide linear detection 233 range, performance test with clinical specimens from suspected COVID-19 patients 234 suggested that the N gene assay in IPBCAMS assays and CCDC assays, and the ORF 235 1b gene assays in IPBCAMS assays were the preferred qRT-PCR assays for accurate 236 detection of SARS-CoV-2. abstract: Quick and accurate detection of SARS-CoV-2 is critical for COVID-19 control. Dozens of real-time reverse transcription PCR (qRT-PCR) assays have been developed to meet the urgent need of COVID-19 control. However, methodological comparisons among the developed qRT-PCR assays are limited. In the present study, we evaluated the sensitivity, specificity, amplification efficiency, and linear detection ranges of three qRT-PCR assays, including the assays developed by our group (IPBCAMS), and the assays recommended by WHO and China CDC (CCDC). The three qRT-PCR assays exhibited similar sensitivities, with the limit of detection (LOD) at about 10 copies per reaction (except the ORF 1b gene assay in CCDC assays with a LOD at about 100 copies per reaction). No cross reaction with other respiratory viruses were observed in all of the three qRT-PCR assays. Wide linear detection ranges from 106 to 101 copies per reaction and acceptable reproducibility were obtained. By using 25 clinical specimens, the N gene assay of IPBCAMS assays and CCDC assays performed better (with detection rates of 92% and 100%, respectively) than that of the WHO assays (with a detection rate of 60%), and the ORF 1b gene assay in IPBCAMS assays performed better (with a detection rate of 64%) than those of the WHO assays and the CCDC assays (with detection rates of 48% and 20%, respectively). In conclusion, the N gene assays of CCDC assays and IPBCAMS assays and the ORF 1b gene assay of IPBCAMS assays were recommended for qRT-PCR screening of SARS-CoV-2. url: https://doi.org/10.1101/2020.07.06.189860 doi: 10.1101/2020.07.06.189860 id: cord-345299-4k7qymqd author: Xiong, Hua-Long title: Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro date: 2020-06-05 words: 1471.0 sentences: 88.0 pages: flesch: 47.0 cache: ./cache/cord-345299-4k7qymqd.txt txt: ./txt/cord-345299-4k7qymqd.txt summary: To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. In this study, the anti-SARS-Cov-2 potentiality of 1403 FDA approved drugs were quantitatively evaluated by the pseudovirus-based assay. In the second round of screening, inhibition of VSV-SARS-CoV-2-Sdel18 virus infection and cell cytotoxicity were both detected (Supplementary Figure 1) . The robust assay based on VSV-SARS-CoV-2-Sdel18 pseudovirus screened out the potential drugs with high efficiency, then the inhibitory effect was confirmed by authentic SARS-CoV-2 assay. The relative value or inhibition rate of candidate drugs were calculated according to the decrease of GFP positive cell number (for pseudovirus-based assay) or cytopathic effect (for authentic SARS-CoV-2-based assay). abstract: To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 μM. url: https://doi.org/10.1101/2020.06.05.135996 doi: 10.1101/2020.06.05.135996 id: cord-345499-hq5um68k author: Xiong, Rui title: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 date: 2020-03-12 words: 5275.0 sentences: 317.0 pages: flesch: 53.0 cache: ./cache/cord-345499-hq5um68k.txt txt: ./txt/cord-345499-hq5um68k.txt summary: title: Novel and potent inhibitors targeting DHODH, a rate-limiting enzyme in de novo pyrimidine biosynthesis, are broad-spectrum antiviral against RNA viruses including newly emerged coronavirus SARS-CoV-2 Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. We identified that targeting DHODH offers broad-spectrum antiviral efficacies against various RNA viruses, including the DAA-resistant influenza virus and the newly emerged coronavirus SARS-CoV-2. abstract: Emerging and re-emerging RNA viruses occasionally cause epidemics and pandemics worldwide, such as the on-going outbreak of coronavirus SARS-CoV-2. Existing direct-acting antiviral (DAA) drugs cannot be applied immediately to new viruses because of virus-specificity, and the development of new DAA drugs from the beginning is not timely for outbreaks. Thus, host-targeting antiviral (HTA) drugs have many advantages to fight against a broad spectrum of viruses, by blocking the viral replication and overcoming the potential viral mutagenesis simultaneously. Herein, we identified two potent inhibitors of DHODH, S312 and S416, with favorable drug-like and pharmacokinetic profiles, which all showed broad-spectrum antiviral effects against various RNA viruses, including influenza A virus (H1N1, H3N2, H9N2), Zika virus, Ebola virus, and particularly against the recent novel coronavirus SARS-CoV-2. Our results are the first to validate that DHODH is an attractive host target through high antiviral efficacy in vivo and low virus replication in DHODH knocking-out cells. We also proposed the drug combination of DAA and HTA was a promising strategy for anti-virus treatment and proved that S312 showed more advantageous than Oseltamivir to treat advanced influenza diseases in severely infected animals. Notably, S416 is reported to be the most potent inhibitor with an EC50 of 17nM and SI value >5882 in SARS-CoV-2-infected cells so far. This work demonstrates that both our self-designed candidates and old drugs (Leflunomide/Teriflunomide) with dual actions of antiviral and immuno-repression may have clinical potentials not only to influenza but also to COVID-19 circulating worldwide, no matter such viruses mutate or not. url: https://doi.org/10.1101/2020.03.11.983056 doi: 10.1101/2020.03.11.983056 id: cord-261877-4y37676n author: Xu, Cong title: Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM date: 2020-06-30 words: 8754.0 sentences: 505.0 pages: flesch: 60.0 cache: ./cache/cord-261877-4y37676n.txt txt: ./txt/cord-261877-4y37676n.txt summary: Recent cryoelectron microscopy (cryo-EM) studies on the stabilized ectodomain of SARS-CoV-2 S protein revealed a closed state of S trimer with three RBD domains in "down" conformation (Walls et al., 2020) , as well as an open state with one RBD in the "up" conformation, corresponding to the receptor-accessible state (Walls et al., 2020; Wrapp et al., 2020) . To gain a thorough picture on how the receptor ACE2 binding induces conformational dynamics of the SARS-CoV-2 S trimer and triggers transition towards the postfusion state, we determine the cryo-EM structure of SARS-CoV-2 S trimer in complex with human ACE2 PD domain to 3.8 Å resolution (termed SARS-CoV-2 S-ACE2, Figs. Based on the data, we put forward a mechanism of ACE2 binding-induced conformational transitions of SARS-CoV-2 S trimer from the tightly closed ground prefusion state transforming towards the postfusion state (Fig. 6) . Cryo-electron microscopy structures of the SARS-CoV spike glycoprotein reveal a prerequisite conformational state for receptor binding abstract: The recent outbreaks of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its rapid international spread pose a global health emergency. The trimeric spike (S) glycoprotein interacts with its receptor human ACE2 to mediate viral entry into host-cells. Here we present cryo-EM structures of an uncharacterized tightly closed SARS-CoV-2 S-trimer and the ACE2-bound-S-trimer at 2.7-Å and 3.8-Å-resolution, respectively. The tightly closed S-trimer with inactivated fusion peptide may represent the ground prefusion state. ACE2 binding to the up receptor-binding domain (RBD) within S-trimer triggers continuous swing-motions of ACE2-RBD, resulting in conformational dynamics of S1 subunits. Noteworthy, SARS-CoV-2 S-trimer appears much more sensitive to ACE2-receptor than SARS-CoV S-trimer in terms of receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. We defined the RBD T470-T478 loop and residue Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2, and provided structural basis of the spike D614G-mutation induced enhanced infectivity. Our findings offer a thorough picture on the mechanism of ACE2-induced conformational transitions of S-trimer from ground prefusion state towards postfusion state, thereby providing important information for development of vaccines and therapeutics aimed to block receptor binding. url: https://doi.org/10.1101/2020.06.30.177097 doi: 10.1101/2020.06.30.177097 id: cord-328257-kl4wh2zg author: Xu, H title: Hydroxychloroquine increased psychiatric-like behaviors and disrupted the expression of related genes in the mouse brain date: 2020-09-28 words: 4851.0 sentences: 217.0 pages: flesch: 54.0 cache: ./cache/cord-328257-kl4wh2zg.txt txt: ./txt/cord-328257-kl4wh2zg.txt summary: Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. Less attention has been paid to the effects of HCQ on mental health, although multiple studies have reported severe psychiatric symptoms, including agitation, hallucinations, anxiety, depression, and suicidal ideation, in patients treated with HCQ or chloroquine (9) (10) (11) (12) . To the best of our knowledge, this study is the first to test the psychiatric effect of HCQ in an animal model, and our results suggest that, in healthy mice, HCQ administration can induce persistent behavioral changes and disrupt gene expression in the brain. Our results did not reveal a significant effect of HCQ treatment on working memory, but total exploration time was decreased after HCQ administration, which also suggests that the drugs increased anxiety. abstract: Hydroxychloroquine (HCQ), which has been proposed as a therapeutic or prophylactic drug for SARS-COV-2, has been administered to thousands of individuals with varying efficacy; however, our understanding of its adverse effects is insufficient. It was reported that HCQ induced psychiatric symptoms in a few patients with autoimmune diseases, but it is still uncertain whether HCQ poses a risk to mental health. Therefore, in this study, we treated healthy mice with two different doses of HCQ that are comparable to clinically administered doses for 7 days. Psychiatric-like behaviors and the expression of related molecules in the brain were evaluated at two time points, i.e., 24 h and 10 days after drug administration. We found that HCQ increased anxiety behavior at both 24 h and 10 days and enhanced depressive behavior at 24 h. Furthermore, HCQ decreased the mRNA expression of interleukin-1beta and corticotropin-releasing hormone (Crh) in the hippocampus and decreased the mRNA expression of brain-derived neurotrophic factor (Bdnf) in both the hippocampus and amygdala. Most of these behavioral and molecular changes were sustained beyond 10 days after drug administration, and some of them were dose-dependent. Although this animal study does not prove that HCQ has a similar effect in humans, it indicates that HCQ poses a significant risk to mental health and suggests that further clinical investigation is essential. According to our data, we recommend that HCQ be carefully used as a prophylactic drug in people who are susceptible to mental disorders. url: https://doi.org/10.1101/2020.09.27.316158 doi: 10.1101/2020.09.27.316158 id: cord-317523-idji1l0a author: Xu, Huanzhou title: SARS-CoV-2 viroporin triggers the NLRP3 inflammatory pathway date: 2020-10-27 words: 1192.0 sentences: 59.0 pages: flesch: 42.0 cache: ./cache/cord-317523-idji1l0a.txt txt: ./txt/cord-317523-idji1l0a.txt summary: With the selective NLRP3 inhibitor MCC950 able to block ORF3a-mediated inflammasome activation and key ORF3a residues needed for virus release and inflammasome activation conserved in SARS-CoV-2 isolates across continents, ORF3a and NLRP3 present prime targets for intervention. In a pared-down system, we investigate the influence of ORF3a, an essential SARS-CoV-2 protein, on the inflammatory machinery and find that it activates NLRP3, the most prominent inflammasome by causing potassium loss across the cell membrane. To assess if ORF3a also 135 mediates activation of other prominent inflammasomes including NLRP1 and NLRC4, we 136 depleted each of these molecules but were unable to block cleavage of pro-caspase 1 (Fig.2G) , 137 indicating that ORF3a predominantly activates the NLRP3 inflammasome. In summary, an essential viroporin required for release of SARS-CoV-2 from infected cells is also 178 able to prime and activate the NLRP3 inflammasome, the machinery responsible for much of the abstract: Cytokine storm resulting from a heightened inflammatory response is a prominent feature of severe COVID-19 disease. This inflammatory response results from assembly/activation of a cell-intrinsic defense platform known as the inflammasome. We report that the SARS-CoV-2 viroporin encoded by ORF3a activates the NLRP3 inflammasome, the most promiscuous of known inflammasomes. ORF3a triggers IL-1β expression via NFκB, thus priming the inflammasome while also activating it via ASC-dependent and -independent modes. ORF3a-mediated inflammasome activation requires efflux of potassium ions and oligomerization between NEK7 and NLRP3. With the selective NLRP3 inhibitor MCC950 able to block ORF3a-mediated inflammasome activation and key ORF3a residues needed for virus release and inflammasome activation conserved in SARS-CoV-2 isolates across continents, ORF3a and NLRP3 present prime targets for intervention. Summary Development of anti-SARS-CoV-2 therapies is aimed predominantly at blocking infection or halting virus replication. Yet, the inflammatory response is a significant contributor towards disease, especially in those severely affected. In a pared-down system, we investigate the influence of ORF3a, an essential SARS-CoV-2 protein, on the inflammatory machinery and find that it activates NLRP3, the most prominent inflammasome by causing potassium loss across the cell membrane. We also define key amino acid residues on ORF3a needed to activate the inflammatory response, and likely to facilitate virus release, and find that they are conserved in virus isolates across continents. These findings reveal ORF3a and NLRP3 to be attractive targets for therapy. url: https://doi.org/10.1101/2020.10.27.357731 doi: 10.1101/2020.10.27.357731 id: cord-103422-ys846i99 author: Xu, Xinhui title: CRISPR-Assisted DNA Detection, a novel dCas9-based DNA detection technique date: 2020-05-13 words: 4258.0 sentences: 308.0 pages: flesch: 60.0 cache: ./cache/cord-103422-ys846i99.txt txt: ./txt/cord-103422-ys846i99.txt summary: In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. When target DNA is bound by a pair of dCas9-sgRNA complexes, the dCas9-sgRNA-DNA complex will be captured on surface of beads or microplate via annealing between an oligonucleotide coupled on solid supports and capture sequence of sgRNAa. Then the captured dCas9-sgRNA-DNA complex is reported by a kind of signal reporter captured by the capture sequence of sgRNAb. This method was validated by detecting DNA of bacteria, cancer cell and virus. We compared the HPV detection results of these 31 clinical samples tested by Beads-HCR CADD and PCR-reverse dot hybridization method that was performed by Jinling Hospital (Fig. 4C ). These results indicate that Beads-HCR CADD can be used to detect hrHPV infections in clinical samples with high sensitivity and specificity. abstract: Nucleic acid detection techniques are always critical to diagnosis, especially in the background of the present COVID-19 pandemic. The simple and rapid detection techniques with high sensitivity and specificity are always urgently needed. However, the current nucleic acid detection techniques are still limited the traditional amplification and hybridization. To overcome the limitation, we here develop a CRISPR/Cas9-assisted DNA detection (CADD). In this detection, DNA sample is incubated with a pair of capture sgRNAs (sgRNAa and sgRNAb) specific to a target DNA, dCas9, a signal readout-related probe, and an oligo-coated solid support beads or microplate at room temperature for 15 min. During this incubation, the dCas9-sgRNA-DNA complex is formed and captured on solid support by the capture sequence of sgRNAa and the signal readout-related probe is captured by the capture sequence of sgRNAb. Finally the detection result is reported by a fluorescent or colorimetric signal readout. This detection was verified by detecting DNA of bacteria, cancer cell and virus. Especially, by designing a set of sgRNAs specific to 15 high-risk human papillomaviruses (HPVs), the HPV infection in 64 clinical cervical samples were successfully detected by the method. All detections can be finished in 30 minutes at room temperature. This detection holds promise for rapid on-the-spot detection or point-of-care testing (POCT). url: https://doi.org/10.1101/2020.05.13.093062 doi: 10.1101/2020.05.13.093062 id: cord-344560-662pfa61 author: Yamamoto, Norio title: Nelfinavir inhibits replication of severe acute respiratory syndrome coronavirus 2 in vitro date: 2020-04-08 words: 1419.0 sentences: 96.0 pages: flesch: 71.0 cache: ./cache/cord-344560-662pfa61.txt txt: ./txt/cord-344560-662pfa61.txt summary: After the outbreak of severe acute respiratory syndrome (SARS) in 2003, screening of approved drugs identified at least two human immunodeficiency virus type-1 (HIV-1) protease inhibitors, lopinavir and nelfinavir, as compounds that inhibited SARS-CoV replication in vitro 3, 4 . Among these inhibitors tested, the high concentrations of drugs were required to inhibit SARS-CoV-2 replication in amprenavir (EC 50 = 31.32 µM, CC 50 > 81 µM, SI > 2.59), darunavir (EC 50 = 46.41 µM, CC 50 > 81 µM, SI > 1.75), and indinavir (EC 50 = 59.14 µM CC 50 > 81 µM, SI > 1.37) (Fig. 1g , h, i, j). Lopinavir, which has been clinically tested in patients with SARS and COVID-19, blocked SARS-CoV-2 replication at a low concentration range and its SI was relatively high among nine inhibitors (EC 50 = 5.73 µM, CC 50 = 74.44 µM, SI = 12.99) (Fig. 1b, j) . These results suggest that nelfinavir, lopinavir, and tipranavir can achieve EC 50 of each drug in human and are effective in the treatment of COVID-19 patients. abstract: In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against coronavirus disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the treatment of this disease, and several approved drugs such as lopinavir have been evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication of SARS-CoV-2. The effective concentrations for 50% and 90% inhibition (EC50 and EC90) of nelfinavir were 1.13 µM and 1.76 µM respectively, the lowest of the nine HIV-1 protease inhibitors including lopinavir. The trough and peak serum concentrations of nelfinavir were three to six times higher than EC50 of this drug. These results suggest that nelfinavir is a potential candidate drug for the treatment of COVID-19 and should be assessed in patients with COVID-19. url: https://doi.org/10.1101/2020.04.06.026476 doi: 10.1101/2020.04.06.026476 id: cord-295560-0rpguepv author: Yan, Kexin title: Simple rapid in vitro screening method for SARS-CoV-2 anti-virals that identifies potential cytomorbidity-associated false positives date: 2020-10-14 words: 1883.0 sentences: 99.0 pages: flesch: 55.0 cache: ./cache/cord-295560-0rpguepv.txt txt: ./txt/cord-295560-0rpguepv.txt summary: The assay clearly illustrated the anti-viral activity of remdesivir, a drug known to inhibit SARS-CoV-2 replication. Here we describe a simple rapid bioassay for drug screening using Vero 20 E6 cells and inhibition of cytopathic effects (CPE) measured using crystal violet staining. A key refinement involves a simple growth assay to identify drug concentrations that 23 cause cellular stress or "cytomorbidity", as distinct from cytotoxicity or loss of viability. A key refinement involves a simple growth assay to identify drug concentrations that 23 cause cellular stress or "cytomorbidity", as distinct from cytotoxicity or loss of viability. Thus a drug that has no specific anti-viral activity, but that 52 is able to induce cellular stress, may therefore inhibit virus replication non-specifically and generate 53 a potential false positive in the screening assay. A simple rapid bioassay for screening drugs for potential antiviral activity against SARS-CoV-2 72 is to determine whether the drug can inhibit virus-induced cytopathic effects (CPE) in Vero E6 cells. abstract: The international SARS-CoV-2 pandemic has resulted in an urgent need to identify new anti-viral drugs for treatment of COVID-19 patients. The initial step to identifying potential candidates usually involves in vitro screening. Here we describe a simple rapid bioassay for drug screening using Vero E6 cells and inhibition of cytopathic effects (CPE) measured using crystal violet staining. The assay clearly illustrated the anti-viral activity of remdesivir, a drug known to inhibit SARS-CoV-2 replication. A key refinement involves a simple growth assay to identify drug concentrations that cause cellular stress or “cytomorbidity”, as distinct from cytotoxicity or loss of viability. For instance, hydroxychloroquine shows anti-viral activity at concentrations that slow cell growth, arguing that its purported in vitro anti-viral activity arises from non-specific impairment of cellular activities. url: https://doi.org/10.1101/2020.10.13.338541 doi: 10.1101/2020.10.13.338541 id: cord-259620-qigfstxt author: Yang, Chen title: Kidney injury molecule-1 is a potential receptor for SARS-CoV-2 date: 2020-10-10 words: 3373.0 sentences: 205.0 pages: flesch: 54.0 cache: ./cache/cord-259620-qigfstxt.txt txt: ./txt/cord-259620-qigfstxt.txt summary: Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Studies have indicated direct infection of SARS-CoV-2 in kidney in addition to lung 5, 31 , however, ACE2 remains the only confirmed receptor which may mediate this invasion. Notably, our results suggest that SARS-CoV-2-RBD binds KIM1 and ACE2 via two distinct pockets, implicating that KIM1 and ACE2 may synergistically mediate the invasion of SARS-CoV-2 in kidney cells; which may explain the strong renal tropism, as well as the high incidence of acute kidney injury in COVID-19 patients 5 . ACE2 is the most well-studied receptor for SARS-CoV-2 so far, yet it is not an ideal therapeutic target for COVID-19 since it is widely expresses in multiple organs, and plays crucial roles in regulating blood pressure and preventing heart/kidney injury 36, 37 . abstract: COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and high mortality. Identification of SARS-CoV-2 in kidney of COVID-19 patients suggests renal tropism and direct infection. Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Kidney injury molecule-1 (KIM1) is a transmembrane protein that drastically up-regulated after renal injury. Here, binding between SARS-CoV2-RBD and the extracellular Ig V domain of KIM1 was identified by molecular simulations and co-immunoprecipitation, which was comparable in affinity to that of ACE2 to SARS-CoV-2. Moreover, KIM1 facilitated cell entry of SARS-CoV2-RBD, which was potently blockaded by a rationally designed KIM1-derived polypeptide. Together, the findings suggest KIM1 may mediate and exacerbate SARS-CoV-2 infection in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target. url: https://doi.org/10.1101/2020.10.09.334052 doi: 10.1101/2020.10.09.334052 id: cord-293428-8hj06hzt author: Yang, Jianling title: Cytotoxicity evaluation of chloroquine and hydroxychloroquine in multiple cell lines and tissues by dynamic imaging system and PBPK model date: 2020-04-24 words: 1855.0 sentences: 88.0 pages: flesch: 53.0 cache: ./cache/cord-293428-8hj06hzt.txt txt: ./txt/cord-293428-8hj06hzt.txt summary: To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung. Recent 99 publications have demonstrated that chloroquine (CQ) and hydroxychloroquine (HCQ) 100 efficiently inhibited SARS-CoV-2 infection in vitro assay (7-9). The data suggest that HCQ was 127 demonstrated to be much less toxic than CQ, at least at certain key tissues (heart, liver, 128 kidney, and lung). However, the tissue trough concentration of 197 HCQ in lung is the highest level (25.633 μg/ml) compared with liver, kidney and heart 198 (Table 2 and Figure 4 ). Hydroxychloroquine, a less toxic derivative of chloroquine, is effective in inhibiting 286 SARS-CoV-2 infection in vitro abstract: Chloroquine (CQ) and hydroxychloroquine (HCQ) have been used in treating COVID-19 patients recently. However, both drugs have some contradictions and rare but severe side effects, such as hypoglycemia, retina and cardiac toxicity. To further uncover the toxicity profile of CQ and HCQ in different tissues, we evaluated the cytotoxicity of them in 8 cell lines, and further adopted the physiologically-based pharmacokinetic models (PBPK) to predict the tissue risk respectively. Retina, myocardium, lung, liver, kidney, vascular endothelium and intestinal epithelium originated cells were included in the toxicity evaluation of CQ and HCQ respectively. The proliferation pattern was monitored in 0-72 hours by IncuCyte S3, which could perform long-term continuous image and video of cells upon CQ or HCQ treatment. CC50 and the ratio of tissue trough concentrations to CC50 (RTTCC) were brought into predicted toxicity profiles. The CC50 at 24 h, 48 h, 72 h of CQ and HCQ decreased in the time-dependent manner, which indicates the accumulative cytotoxic effect. HCQ was found to be less toxic in 7 cell types except cardiomyocytes H9C2 cells (CC50-48 h=29.55 μM; CC50-72 h=15.26 μM). In addition, RTTCC is significant higher in CQ treatment group compared to HCQ group, which indicates that relative safety of HCQ. Both CQ and HCQ have certain cytotoxicity in time dependent manner which indicates the necessity of short period administration clinically. HCQ has the less impact in 7 cell lines proliferation and less toxicity compared to CQ in heart, liver, kidney and lung. url: https://doi.org/10.1101/2020.04.22.056762 doi: 10.1101/2020.04.22.056762 id: cord-103869-ii6qi1bp author: Yang, Liu title: Defining a Global Map of Functional Group Based 3D Ligand-binding Motifs date: 2020-09-28 words: 7435.0 sentences: 386.0 pages: flesch: 51.0 cache: ./cache/cord-103869-ii6qi1bp.txt txt: ./txt/cord-103869-ii6qi1bp.txt summary: Current methods based on structural comparison or alignment of protein pockets have identified many well-defined 3D motifs that are conserved across different protein pockets and widely used for protein function annotation, pockets classification and ligand-binding prediction (Gao and Skolnick, 2013; Hoffmann et al., 2010; Hwang et al., 2017; Pires et al., 2013; Pu et al., 2019; Yeturu and Chandra, 2008) . To systematically identify and evaluate 3D binding motifs at FG level, we developed AFTME, an alignment-free method that automatically maps functional atoms to different FGs from a set of protein pockets binding the same ligand using two-dimensional clustering approach. We have developed AFTME, a computational method to dissect protein pockets binding a specific ligand into sectors that interact with different functional groups (FGs). The basic assumption of this method is simple: if conserved binding pattern for a specific FG exists, the pattern-forming atoms should be spatially proximal to the corresponding FG and frequently co-appear, thus can be detected through clustering analysis of functional atoms from diverse protein pockets binding the same ligand. abstract: Uncovering conserved 3D protein-ligand binding patterns at the basis of functional groups (FGs) shared by a variety of small molecules can greatly expand our knowledge of protein-ligand interactions. Despite that conserved binding patterns for a few commonly used FGs have been reported in the literature, large-scale identification and evaluation of FG-based 3D binding motifs are still lacking. Here, we developed AFTME, an alignment-free method for automatic mapping of 3D motifs to different FGs of a specific ligand through two-dimensional clustering. Applying our method to 233 nature-existing ligands, we defined 481 FG-binding motifs that are highly conserved across different ligand-binding pockets. Systematic analysis further reveals four main classes of binding motifs corresponding to distinct sets of FGs. Combinations of FG-binding motifs facilitate proteins to bind a wide spectrum of ligands with various binding affinities. Finally, we showed that these general binding patterns are also applicable to target-drug interactions, providing new insights into structure-based drug design. url: https://doi.org/10.1101/2020.09.27.315762 doi: 10.1101/2020.09.27.315762 id: cord-261688-njlxrxv6 author: Yang, Ziwei title: Suppression of MDA5-mediated antiviral immune responses by NSP8 of SARS-CoV-2 date: 2020-08-12 words: 2508.0 sentences: 166.0 pages: flesch: 52.0 cache: ./cache/cord-261688-njlxrxv6.txt txt: ./txt/cord-261688-njlxrxv6.txt summary: Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. Here, we revealed that NSP8 protein of SARS-CoV-2 directly blocks the activation of the cytosolic viral dsRNA sensor MDA5 and significantly downregulates antiviral immune responses. Our study contributes to our understanding of the direct immune evasion mechanism of SARS-CoV-2 by showing that NSP8 suppresses the most upstream sensor of innate immune responses involved in the recognition of viral dsRNA. Based on our existing experimental data, we propose a simple working model to illustrate how NSP8 218 negatively regulates innate immune responses by inhibiting MDA5 K63-linked polyubiquitination (Fig.5c) . abstract: Melanoma differentiation-associated gene-5 (MDA5) acts as a cytoplasmic RNA sensor to detect viral dsRNA and mediates type I interferon (IFN) signaling and antiviral innate immune responses to infection by RNA viruses. Upon recognition of viral dsRNA, MDA5 is activated with K63-linked polyubiquitination and then triggers the recruitment of MAVS and activation of TBK1 and IKK, subsequently leading to IRF3 and NF-κB phosphorylation. Great numbers of symptomatic and severe infections of SARS-CoV-2 are spreading worldwide, and the poor efficacy of treatment with type I interferon and antiviral agents indicates that SARS-CoV-2 escapes from antiviral immune responses via an unknown mechanism. Here, we report that SARS-CoV-2 nonstructural protein 8 (NSP8) acts as an innate immune suppressor and inhibits type I IFN signaling to promote infection of RNA viruses. It downregulates the expression of type I IFNs, IFN-stimulated genes and proinflammatory cytokines by binding to MDA5 and impairing its K63-linked polyubiquitination. Our findings reveal that NSP8 mediates innate immune evasion during SARS-CoV-2 infection and may serve as a potential target for future therapeutics for SARS-CoV-2 infectious diseases. Importance The large-scale spread of COVID-19 is causing mass casualties worldwide, and the failure of antiviral immune treatment suggests immune evasion. It has been reported that several nonstructural proteins of severe coronaviruses suppress antiviral immune responses; however, the immune suppression mechanism of SARS-CoV-2 remains unknown. Here, we revealed that NSP8 protein of SARS-CoV-2 directly blocks the activation of the cytosolic viral dsRNA sensor MDA5 and significantly downregulates antiviral immune responses. Our study contributes to our understanding of the direct immune evasion mechanism of SARS-CoV-2 by showing that NSP8 suppresses the most upstream sensor of innate immune responses involved in the recognition of viral dsRNA. url: https://doi.org/10.1101/2020.08.12.247767 doi: 10.1101/2020.08.12.247767 id: cord-102364-t5bt2eb4 author: Yao, Dehui title: Human H-ferritin presenting RBM of spike glycoprotein as potential vaccine of SARS-CoV-2 date: 2020-06-08 words: 1852.0 sentences: 104.0 pages: flesch: 54.0 cache: ./cache/cord-102364-t5bt2eb4.txt txt: ./txt/cord-102364-t5bt2eb4.txt summary: In an effort of utilizing human ferritin as nanoplatform for drug delivery, we engineered a fusion protein by presenting receptor-binding motif (RBM) of SARS-CoV-2 virus spike glycoprotein on the N-terminus of ferritin subunits. The designed fusion protein with a cage-like structure, similar to that of corona virus, is a potential anti-SARS-CoV-2 vaccine. We hereby show the construction, preparation, and characterization of the fusion protein RBM-HFtn. Our initial affinity study confirmed its biological activity towards ACE2 receptor which suggests its mode of action against SARS-CoV-2 could be either through vaccine therapy or blocking the cellular entry of virus as antagonist of ACE2 receptor. Antibodies targeting the spike glycoprotein of SARS-CoV and MERS-CoV, especially its receptor-binding domain (RBD), was found to efficiently neutralize virus infection [1, 2] . In this work, we engineered a human ferritin heavy chain (HFtn) by fusing and presenting the RBM of its spike glycoprotein as potential vaccine of SARS-CoV-2. abstract: The outbreak of COVID-19 has so far inflicted millions of people all around the world and will have a long lasting effect on every aspect of everyone’s life. Yet there is no effective approved treatment for the disease. In an effort of utilizing human ferritin as nanoplatform for drug delivery, we engineered a fusion protein by presenting receptor-binding motif (RBM) of SARS-CoV-2 virus spike glycoprotein on the N-terminus of ferritin subunits. The designed fusion protein with a cage-like structure, similar to that of corona virus, is a potential anti-SARS-CoV-2 vaccine. We hereby show the construction, preparation, and characterization of the fusion protein RBM-HFtn. Our initial affinity study confirmed its biological activity towards ACE2 receptor which suggests its mode of action against SARS-CoV-2 could be either through vaccine therapy or blocking the cellular entry of virus as antagonist of ACE2 receptor. url: https://doi.org/10.1101/2020.05.25.115618 doi: 10.1101/2020.05.25.115618 id: cord-354868-pqn59ojj author: Yao, Hebang title: A high-affinity RBD-targeting nanobody improves fusion partner’s potency against SARS-CoV-2 date: 2020-09-25 words: 3231.0 sentences: 236.0 pages: flesch: 58.0 cache: ./cache/cord-354868-pqn59ojj.txt txt: ./txt/cord-354868-pqn59ojj.txt summary: title: A high-affinity RBD-targeting nanobody improves fusion partner''s potency against SARS-CoV-2 Considerable research have been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. A high-affinity RBD binder without neutralizing activity 85 Previously, we generated 99 sybodies from three highly diverse synthetic libraries by ribosome and phage display with in vitro selections against the SARS-CoV-2 RBD. Consistent with its inability to neutralize SARS-CoV-2 pseudovirus, SR31 did not affect RBD-ACE2 binding (Fig. 1C) . Most RBD-targeting neutralizing antibodies, including neutralizing nanobodies characterized so far (8, 13-15, 19, 20, 22-24, 26-28, 34, 35, 37) , engage the RBD at the receptor-binding motif (RBM) (Fig. 3A) , thus competing off ACE2 and preventing viral entry. Taken together, the structural data rationalize the high-affinity binding between SR31 and RBD, and its inability to neutralize SARS-CoV-2. Neutralizing nanobodies bind SARS-CoV-2 spike RBD and block interaction with ACE2 abstract: A key step to the SARS-CoV-2 infection is the attachment of its Spike receptor-binding domain (S RBD) to the host receptor ACE2. Considerable research have been devoted to the development of neutralizing antibodies, including llama-derived single-chain nanobodies, to target the receptor-binding motif (RBM) and to block ACE2-RBD binding. Simple and effective strategies to increase potency are desirable for such studies when antibodies are only modestly effective. Here, we identify and characterize a high-affinity synthetic nanobody (sybody, SR31) as a fusion partner to improve the potency of RBM-antibodies. Crystallographic studies reveal that SR31 binds to RBD at a conserved and ‘greasy’ site distal to RBM. Although SR31 distorts RBD at the interface, it does not perturb the RBM conformation, hence displaying no neutralizing activities itself. However, fusing SR31 to two modestly neutralizing sybodies dramatically increases their affinity for RBD and neutralization activity against SARS-CoV-2 pseudovirus. Our work presents a tool protein and an efficient strategy to improve nanobody potency. url: https://doi.org/10.1101/2020.09.24.312595 doi: 10.1101/2020.09.24.312595 id: cord-356005-zhwtlik6 author: Yazhini, Arangasamy title: D614G substitution enhances the stability of trimeric SARS-CoV-2 spike protein date: 2020-11-02 words: 2626.0 sentences: 142.0 pages: flesch: 47.0 cache: ./cache/cord-356005-zhwtlik6.txt txt: ./txt/cord-356005-zhwtlik6.txt summary: Here, using in-silico mutagenesis and energy calculations, we analyzed inter-residue interaction energies and thermodynamic stability of the dominant (G614) and the ancestral (D614) variants of spike protein trimer in ''closed'' and ''partially open'' conformations. Such changes in the local interaction energies enhance the thermodynamic stability of the spike protein trimer as free energy difference (ΔΔG) upon glycine substitution is −2.6 kcal/mol for closed conformation and −2.0 kcal/mol for open conformation. Our results on the structural and energetic basis of enhanced stability hint that G614 may confer increased availability of functional form of spike protein trimer and consequent in higher infectivity than the D614 variant. To study the effect of D614G variation on the thermodynamic stability of the spike protein trimer, we calculated free energy changes upon aspartate to glycine substitution using buildmodel function in FoldX (Schymkowitz et al., 2005) . The table contains details of frustration index of inter-residue contacts present at 614th position of spike protein trimer in closed and partially open conformations. abstract: SARS-CoV-2 spike protein with D614G substitution has become the dominant variant in the ongoing COVID-19 pandemic. Several studies to characterize the new virus expressing G614 variant show that it exhibits increased infectivity compared to the ancestral virus having D614 spike protein. Here, using in-silico mutagenesis and energy calculations, we analyzed inter-residue interaction energies and thermodynamic stability of the dominant (G614) and the ancestral (D614) variants of spike protein trimer in ‘closed’ and ‘partially open’ conformations. We find that the local interactions mediated by aspartate at the 614th position are energetically frustrated and create unfavourable environment. Whereas, glycine at the same position confers energetically favourable environment and strengthens intra-as well as inter-protomer association. Such changes in the local interaction energies enhance the thermodynamic stability of the spike protein trimer as free energy difference (ΔΔG) upon glycine substitution is −2.6 kcal/mol for closed conformation and −2.0 kcal/mol for open conformation. Our results on the structural and energetic basis of enhanced stability hint that G614 may confer increased availability of functional form of spike protein trimer and consequent in higher infectivity than the D614 variant. url: https://doi.org/10.1101/2020.11.02.364273 doi: 10.1101/2020.11.02.364273 id: cord-291012-y0ufzx93 author: Ye, Qing title: SARS-CoV-2 infection causes transient olfactory dysfunction in mice date: 2020-11-10 words: 1846.0 sentences: 125.0 pages: flesch: 51.0 cache: ./cache/cord-291012-y0ufzx93.txt txt: ./txt/cord-291012-y0ufzx93.txt summary: Robust viral nucleocapsid (N) protein was detected in the 89 lung from SARS-CoV-2 infected hACE2 mice, but not from the control animals 90 ( Figure S1B ). Remarkably, a significantly increased latency (152.8 s v.s. 81.8 s; p=0.022) to locate 103 food pellets was observed in SARS-CoV-2 infected mice as compared with the control 104 animals on 2 dpi ( Figure 1D ). Further RT-qPCR assay showed a dozen of 211 OR genes were significantly down regulated in response to SARS-CoV-2 infection 212 ( Figure 5E ), which may also attribute to the observed olfactory dysfunction. Interestingly, SARS-CoV-2 positive signals were also observed in mOSNs and HBCs 245 of infected animals, although we didn''t detect any hACE2 expression in these cells. A) Representative multiplex immunofluorescent staining shows SARS-CoV-2 674 (SARS-CoV-2 N protein-positive) infects sustentacular cells (CK8-positive, yellow 675 arrows), Bowman''s gland cells (Sox9/CK8-positive, white arrows), microvillar cells 676 (CD73/CK8-positive, cyan arrows), HBCs (CK5-postitive, gold arrows) and iOSNs 677 (GAP43-positive abstract: Olfactory dysfunction caused by SARS-CoV-2 infection represents as one of the most predictive and common symptoms in COVID-19 patients. However, the causal link between SARS-CoV-2 infection and olfactory disorders remains lacking. Herein we demonstrate intranasal inoculation of SARS-CoV-2 induces robust viral replication in the olfactory epithelium (OE), resulting in transient olfactory dysfunction in humanized ACE2 mice. The sustentacular cells and Bowman’s gland cells in OE were identified as the major targets of SARS-CoV-2 before the invasion into olfactory sensory neurons. Remarkably, SARS-CoV-2 infection triggers cell death and immune cell infiltration, and impairs the uniformity of OE structure. Combined transcriptomic and proteomic analyses reveal the induction of antiviral and inflammatory responses, as well as the downregulation of olfactory receptors in OE from the infected animals. Overall, our mouse model recapitulates the olfactory dysfunction in COVID-19 patients, and provides critical clues to understand the physiological basis for extrapulmonary manifestations of COVID-19. url: https://doi.org/10.1101/2020.11.10.376673 doi: 10.1101/2020.11.10.376673 id: cord-321427-bwcpd6im author: Yee, Min title: Neonatal hyperoxia enhances age-dependent expression of SARS-CoV-2 receptors in mice date: 2020-07-22 words: 2154.0 sentences: 114.0 pages: flesch: 58.0 cache: ./cache/cord-321427-bwcpd6im.txt txt: ./txt/cord-321427-bwcpd6im.txt summary: Instead, we made the surprising discovery that expression of Ace2 and Tmprss2 mRNA increases as mice age and is accelerated by exposing mice to neonatal hyperoxia. Our finding that early life insults such as hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in the respiratory epithelium helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities. When quantified, neonatal hyperoxia increased the number of alveolar cells expressing ACE2 by 148 approximately 50% at 2, 6 and 12 months of age (Figure 4b) . The levels of Tmprss2 mRNA and protein were examined in the lungs of 2-, 12-and 18-month-old mice that were exposed to neonatal hyperoxia and room air from PND0-4 by qRT-PCR 168 and western blotting. As observed for Ace2 expression, 173 exposure to ≥ 60% oxygen from PND4-0 was required to significantly increase the levels of Tmprss2 174 mRNA in the lungs of mice at 2 months of age (Figure 6c ). abstract: The severity of COVID-19 lung disease is higher in the elderly and people with pre-existing co-morbidities. People who were born preterm may be at greater risk for COVID-19 because their early exposure to oxygen at birth increases their risk of being hospitalized when infected with RSV and other respiratory viruses. Our prior studies in mice showed how high levels of oxygen (hyperoxia) between postnatal days 0–4 increases the severity of influenza A virus infections by reducing the number of alveolar epithelial type 2 (AT2) cells. Because AT2 cells express the SARS-CoV-2 receptors angiotensin converting enzyme (ACE2) and transmembrane protease/serine subfamily member 2 (TMPRSS2), we expected their expression would decline as AT2 cells were depleted by hyperoxia. Instead, we made the surprising discovery that expression of Ace2 and Tmprss2 mRNA increases as mice age and is accelerated by exposing mice to neonatal hyperoxia. ACE2 is primarily expressed at birth by airway Club cells and becomes detectable in AT2 cells by one year of life. Neonatal hyperoxia increases ACE2 expression in Club cells and makes it detectable in 2-month-old AT2 cells. This early and increased expression of SARS-CoV-2 receptors was not seen in adult mice who had been administered the mitochondrial superoxide scavenger mitoTEMPO during hyperoxia. Our finding that early life insults such as hyperoxia enhances the age-dependent expression of SARS-CoV-2 receptors in the respiratory epithelium helps explain why COVID-19 lung disease is greater in the elderly and people with pre-existing co-morbidities. url: https://doi.org/10.1101/2020.07.22.215962 doi: 10.1101/2020.07.22.215962 id: cord-103540-x18pz2uz author: Yellman, Christopher M. title: Precise replacement of Saccharomyces cerevisiae proteasome genes with human orthologs by an integrative targeting method date: 2020-03-26 words: 6426.0 sentences: 335.0 pages: flesch: 49.0 cache: ./cache/cord-103540-x18pz2uz.txt txt: ./txt/cord-103540-x18pz2uz.txt summary: title: Precise replacement of Saccharomyces cerevisiae proteasome genes with human orthologs by an integrative targeting method We used the IT method to introduce phosphorylation site mutations into the gene SPO12 from oligonucleotide repair templates, and to precisely replace essential yeast proteasome genes with their human orthologs. The cassettes, amplified by PCR with flanking target identity, can be integrated into a yeast chromosomal target locus by high-efficiency transformation 36 and selected for by complementation of a ura3 mutation in the host strain. We have previously shown, in plasmid-based complementation tests, that many human genes encoding subunits of the proteasome can functionally replace their yeast orthologs under the control of a strong constitutive yeast promoter and terminator 30 . The IT4 cassettes were then replaced by inducing I-SceI and transforming with PCR-amplified human ORFs, flanked by homology to the promoter and terminator of the yeast gene. abstract: Artificial induction of a chromosomal double-strand break in Saccharomyces cerevisiae enhances the frequency of integration of homologous DNA fragments into the broken region by up to several orders of magnitude. The process of homologous repair can be exploited to integrate, in principle, any foreign DNA into a target site, provided the introduced DNA is flanked at both the 5’ and 3’ ends by sequences homologous to the region surrounding the double-strand break. We have developed a tool set that requires a minimum of steps to induce double-strand breaks at chromosomal target sites with the meganuclease I-SceI and select integration events at those sites. We demonstrate this method in two different applications. First, the introduction of site-specific single-nucleotide phosphorylation site mutations into the S. cerevisiae gene SPO12. Second, the precise chromosomal replacement of eleven S. cerevisiae proteasome genes with their human orthologs. Placing the human genes under S. cerevisiae transcriptional control allowed us to update our of model of functional replacement. Our experience suggests that using native promoters may be a useful general strategy for the coordinated expression of foreign genes in S. cerevisiae. We provide an integrative targeting toolset that will facilitate a variety of precision genome engineering applications. url: https://doi.org/10.1101/2020.03.25.006262 doi: 10.1101/2020.03.25.006262 id: cord-263008-w6twrjzr author: Yin, Rui title: Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide date: 2020-07-15 words: 3684.0 sentences: 213.0 pages: flesch: 48.0 cache: ./cache/cord-263008-w6twrjzr.txt txt: ./txt/cord-263008-w6twrjzr.txt summary: title: Alignment-free machine learning approaches for the lethality prediction of potential novel human-adapted coronavirus using genomic nucleotide We developed alignment-free machine learning approaches for an ultra-fast and highly accurate prediction of the lethality of potential human-adapted coronavirus using genomic nucleotide. We performed extensive experiments through six different feature transformation and machine learning algorithms in combination with digital signal processing to infer the lethality of possible future novel coronaviruses using previous existing strains. The results demonstrate that, for any novel human coronavirus strains, this alignment-free machine learning-based approach can offer a reliable real-time estimation for its viral lethality. In this paper, we propose alignment-free machine learning-based approaches to infer 81 2/18 the lethality of potential novel human-adapted coronavirus using genomic sequences. We provide a comprehensive analysis through alignment-free machine learning-based 385 methods for the prediction of the lethality of potential human-adapted coronavirus. abstract: A newly emerging novel coronavirus appeared and rapidly spread worldwide and World Health Organization declared a pandemic on March 11, 2020. The roles and characteristics of coronavirus have captured much attention due to its power of causing a wide variety of infectious diseases, from mild to severe on humans. The detection of the lethality of human coronavirus is key to estimate the viral toxicity and provide perspective for treatment. We developed alignment-free machine learning approaches for an ultra-fast and highly accurate prediction of the lethality of potential human-adapted coronavirus using genomic nucleotide. We performed extensive experiments through six different feature transformation and machine learning algorithms in combination with digital signal processing to infer the lethality of possible future novel coronaviruses using previous existing strains. The results tested on SARS-CoV, MERS-Cov and SARS-CoV-2 datasets show an average 96.7% prediction accuracy. We also provide preliminary analysis validating the effectiveness of our models through other human coronaviruses. Our study achieves high levels of prediction performance based on raw RNA sequences alone without genome annotations and specialized biological knowledge. The results demonstrate that, for any novel human coronavirus strains, this alignment-free machine learning-based approach can offer a reliable real-time estimation for its viral lethality. url: https://doi.org/10.1101/2020.07.15.176933 doi: 10.1101/2020.07.15.176933 id: cord-102350-e1vc2q4j author: Yoon, Hye-Jin title: Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation date: 2020-06-09 words: 4968.0 sentences: 269.0 pages: flesch: 50.0 cache: ./cache/cord-102350-e1vc2q4j.txt txt: ./txt/cord-102350-e1vc2q4j.txt summary: title: Signature of N-terminal domain (NTD) structural re-orientation in NPC1 for proper alignment of cholesterol transport: Molecular dynamics study with mutation We report the extensive molecular dynamics simulations to gain insight into the structure and motions of NPC1 lumenal domain for cholesterol transport and disease behind the mutation (R518W). In this paper, we present extensive molecular dynamics simulations of NPC1 to understand the structural and dynamical characteristics upon R518W mutation and its effects on overall cholesterol transport efficiency in connection with possible re-location or orientation of NTD and interaction of NPC1 with NPC2. The recent molecular dynamics simulation [30] with full NPC1 when cholesterol is present in NPC1 inhibiting itraconazole binding site, [28] which is at the interface between membrane and lumenal region, shows there is non-negligible distance correlation coefficient between TMD and the rest of the domains. abstract: The lysosomal membrane protein NPC1 (Niemann-Pick type C1) and NPC2 (Niemann-Pick type C2) are main players of cholesterol control in lysosome and it is known that mutation on these proteins leads to cholesterol trafficking related disease, called Niemann-Pick disease type C (NPC) disease. The mutation R518W or R518Q on NPC1 is one of such disease-related mutations, causing reduced cholesterol transport by half, resulting in accumulation of cholesterol and lipids in late endosomal/lysosomal region of the cell. Even though there has been significant progress in understanding cholesterol transport by NPC1 in combination with NPC2, especially after the structural determination of full length NPC1 in 2016, many details such as interaction of full length NPC1 with NPC2, molecular motions responsible for cholesterol transport during and after this interaction, and structure and function relations of many mutations are still not well understood. We report the extensive molecular dynamics simulations to gain insight into the structure and motions of NPC1 lumenal domain for cholesterol transport and disease behind the mutation (R518W). It is found that the mutation induces structural shift of NTD (N-terminal domain), toward the loop region in MLD (middle lumenal domain), which is believed to play central role in interaction with NPC2 protein, such that the interaction with NPC2 protein might be less favorable compare to wild NPC1. Also, the simulation indicates the possible re-orientation of the NTD, aligning to form an internal tunnel, after receiving the cholesterol from NPC2 with wild NPC1 unlike the mutated one, a possible pose for further action in cholesterol trafficking. We believe the current study can provide better understanding on the cholesterol transport by NPC1, especially the role of NTD of NPC1, in combination with NPC2 interaction. Synopsis modeling study of cholesterol binding protein NPC1 url: https://doi.org/10.1101/2020.06.09.141630 doi: 10.1101/2020.06.09.141630 id: cord-282372-nmii30mc author: Youk, Jeonghwan title: Robust three-dimensional expansion of human adult alveolar stem cells and SARS-CoV-2 infection date: 2020-07-10 words: 5124.0 sentences: 294.0 pages: flesch: 53.0 cache: ./cache/cord-282372-nmii30mc.txt txt: ./txt/cord-282372-nmii30mc.txt summary: Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Although basic molecular mechanisms in SARS-CoV-2 infection have been identified [5] [6] [7] [8] , most findings have been obtained from experiments using non-physiological cell lines 9 , model animals, such as transgenic mice expressing human angiotensin-converting enzyme 2 (ACE2) 10 , ferrets 11 and golden hamsters 12 , or from observation in clinical cohorts 13 and/or inference from in-silico computational methods [14] [15] [16] . Immunostaining for double-stranded viral RNA (dsRNA) and nucleocapsid protein (NP) of SARS-CoV-2 identified widespread viral infection in hAT2 cells co-expressing pro-SFTPC and ACE2 in hAOs ( Fig. 2a and 2b; Extended Data Fig. 3) . abstract: Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), which is the cause of a present global pandemic, infects human lung alveolar cells (hACs). Characterising the pathogenesis is crucial for developing vaccines and therapeutics. However, the lack of models mirroring the cellular physiology and pathology of hACs limits the study. Here, we develop a feeder-free, long-term three-dimensional (3D) culture technique for human alveolar type 2 (hAT2) cells, and investigate infection response to SARS-CoV-2. By imaging-based analysis and single-cell transcriptome profiling, we reveal rapid viral replication and the increased expression of interferon-associated genes and pro-inflammatory genes in infected hAT2 cells, indicating robust endogenous innate immune response. Further tracing of viral mutations acquired during transmission identifies full infection of individual cells effectively from a single viral entry. Our study provides deep insights into the pathogenesis of SARS-CoV-2, and the application of long-term 3D hAT2 cultures as models for respiratory diseases. url: https://doi.org/10.1101/2020.07.10.194498 doi: 10.1101/2020.07.10.194498 id: cord-298242-iuskpoug author: Yu, Alvin title: A Multiscale Coarse-grained Model of the SARS-CoV-2 Virion date: 2020-10-02 words: 3604.0 sentences: 204.0 pages: flesch: 47.0 cache: ./cache/cord-298242-iuskpoug.txt txt: ./txt/cord-298242-iuskpoug.txt summary: Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. In this paper, we construct a largely "bottom-up" coarse-grained (CG) model of the SARS-CoV-2 virion from the currently available structural and atomistic simulation data on SARS-CoV-2 proteins. In this work, we detail several of our CG methods used to iteratively develop a CG model for the full SARS-CoV-2 virion, in which molecular interactions between CG particles are derived using a combination of phenomenological, experimental, and atomistic simulation approaches. In recent cryo-EM images of SARS-CoV-2 particles, the S1 domain of the S protein was found to transiently open and close in order to bind the ACE-2 receptor (3, 5) , which are subtle conformational changes that are difficult to sample in atomistic simulations. abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the COVID-19 pandemic. Computer simulations of complete viral particles can provide theoretical insights into large-scale viral processes including assembly, budding, egress, entry, and fusion. Detailed atomistic simulations, however, are constrained to shorter timescales and require billion-atom simulations for these processes. Here, we report the current status and on-going development of a largely “bottom-up” coarse-grained (CG) model of the SARS-CoV-2 virion. Structural data from a combination of cryo-electron microscopy (cryo-EM), x-ray crystallography, and computational predictions were used to build molecular models of structural SARS-CoV-2 proteins, which were then assembled into a complete virion model. We describe how CG molecular interactions can be derived from all-atom simulations, how viral behavior difficult to capture in atomistic simulations can be incorporated into the CG models, and how the CG models can be iteratively improved as new data becomes publicly available. Our initial CG model and the detailed methods presented are intended to serve as a resource for researchers working on COVID-19 who are interested in performing multiscale simulations of the SARS-CoV-2 virion. Significance Statement This study reports the construction of a molecular model for the SARS-CoV-2 virion and details our multiscale approach towards model refinement. The resulting model and methods can be applied to and enable the simulation of SARS-CoV-2 virions. url: https://www.ncbi.nlm.nih.gov/pubmed/33024966/ doi: 10.1101/2020.10.02.323915 id: cord-330743-o11d0aa1 author: Yu, Xi title: Broad-spectrum virucidal activity of bacterial secreted lipases against flaviviruses, SARS-CoV-2 and other enveloped viruses date: 2020-05-25 words: 4470.0 sentences: 245.0 pages: flesch: 54.0 cache: ./cache/cord-330743-o11d0aa1.txt txt: ./txt/cord-330743-o11d0aa1.txt summary: Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Incubation of the culture supernatant but not the bacterial lysates resulted in significant suppression of DENV ( Figure 1B ) and ZIKV ( Figure 1C ) infectivity in Vero cells, indicating that an extracellular effector(s) secreted by Csp_BJ was responsible for viral inhibition. DENV, ZIKV, HSV-1 and SARS-CoV-2 virus stocks were diluted to 50 plaque-forming units (pfu) per ml and incubated untreated or with a serial dilution of the CbAEs in five-fold steps at 37°C for 1 hr before being added onto Vero cell monolayers for 2 hr of infection. abstract: Viruses are the major aetiological agents of acute and chronic severe human diseases that place a tremendous burden on global public health and economy; however, for most viruses, effective prophylactics and therapeutics are lacking, in particular, broad-spectrum antiviral agents. Herein, we identified 2 secreted bacterial lipases from a Chromobacterium bacterium, named Chromobacterium antiviral effector-1 (CbAE-1) and CbAE-2, with a broad-spectrum virucidal activity against dengue virus (DENV), Zika virus (ZIKV), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The CbAEs potently blocked viral infection in the extracellular milieu through their lipase activity. Mechanistic studies showed that this lipase activity directly disrupted the viral envelope structure, thus inactivating infectivity. A mutation of CbAE-1 in its lipase motif fully abrogated the virucidal ability. Furthermore, CbAE-2 presented low toxicity in vivo and in vitro, highlighting its potential as a broad-spectrum antiviral drug. url: https://doi.org/10.1101/2020.05.22.109900 doi: 10.1101/2020.05.22.109900 id: cord-330473-f03ka7bd author: Yuan, Meng title: A highly conserved cryptic epitope in the receptor-binding domains of SARS-CoV-2 and SARS-CoV date: 2020-03-14 words: 1563.0 sentences: 107.0 pages: flesch: 65.0 cache: ./cache/cord-330473-f03ka7bd.txt txt: ./txt/cord-330473-f03ka7bd.txt summary: In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain. A recent study has shown that CR3022, which is a human 49 neutralizing antibody that targets the receptor-binding domain (RBD) of SARS-CoV (4), Nonetheless, despite having a 70 high conservation in the epitope residues, CR3022 Fab binds to SARS-CoV RBD (K d = 1 71 nM) with a much higher affinity than to SARS-CoV-2 RBD (K d = 115 nM) (Table 1 Previous cryo-EM studies have also shown that the recombinant SARS-CoV S 121 protein is mostly found in the none-"up", single-"up", or double-"up" conformations (19, 122 21), but rarely in the triple-"up" conformation, even with ACE2 receptor bound (21, 22) . abstract: The outbreak of COVID-19, which is caused by SARS-CoV-2 virus, continues to spread globally, but there is currently very little understanding of the epitopes on the virus. In this study, we have determined the crystal structure of the receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein in complex with CR3022, a neutralizing antibody previously isolated from a convalescent SARS patient. CR3022 targets a highly conserved epitope that enables cross-reactive binding between SARS-CoV-2 and SARS-CoV. Structural modeling further demonstrates that the binding site can only be accessed when at least two RBDs on the trimeric S protein are in the “up” conformation. Overall, this study provides structural and molecular insight into the antigenicity of SARS-CoV-2. ONE SENTENCE SUMMARY Structural study of a cross-reactive SARS antibody reveals a conserved epitope on the SARS-CoV-2 receptor-binding domain. url: https://doi.org/10.1101/2020.03.13.991570 doi: 10.1101/2020.03.13.991570 id: cord-320054-wqpr8v3p author: Yuan, Xianlin title: The influence of major S protein mutations of SARS-CoV-2 on the potential B cell epitopes date: 2020-08-24 words: 2588.0 sentences: 156.0 pages: flesch: 58.0 cache: ./cache/cord-320054-wqpr8v3p.txt txt: ./txt/cord-320054-wqpr8v3p.txt summary: In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. To explore these questions, here we report 94 to used these immuno-bioinformatic tools from the IEDB and related resources to 95 predict the B cell epitopes of S protein from the prototype and mutated strains of 96 SARS-CoV-2 and compare the changes of the likely epitope sites from dominant and 97 rare mutations of S protein. The major variation sequences were available 409 from The Global Initiative for Sharing All Influenza Data (GISAID) [26] and GenBank 446 We used the sequence from early onset SARS-CoV-2 as the wildtype or prototype and 447 the recent variant virus as mutation strains to predict the B-cell epitopes of S protein. abstract: SARS-CoV-2 has rapidly transmitted worldwide and results in the COVID-19 pandemic. Spike glycoprotein on surface is a key factor of viral transmission, and has appeared a lot of variants due to gene mutations, which may influence the viral antigenicity and vaccine efficacy. Here, we used bioinformatic tools to analyze B-cell epitopes of prototype S protein and its 9 common variants. 12 potential linear and 53 discontinuous epitopes of B-cells were predicted from the S protein prototype. Importantly, by comparing the epitope alterations between prototype and variants, we demonstrate that B-cell epitopes and antigenicity of 9 variants appear significantly different alterations. The dominant D614G variant impacts the potential epitope least, only with moderately elevated antigenicity, while the epitopes and antigenicity of some mutants(V483A, V367F, etc.) with small incidence in the population change greatly. These results suggest that the currently developed vaccines should be valid for a majority of SARS-CoV-2 infectors. This study provides a scientific basis for large-scale application of SARS-CoV-2 vaccines and for taking precautions against the probable appearance of antigen escape induced by genetic variation after vaccination. Author Summary The global pandemic of SARS-CoV-2 has lasted for more than half a year and has not yet been contained. Until now there is no effective treatment for SARS-CoV-2 caused disease (COVID-19). Successful vaccine development seems to be the only hope. However, this novel coronavirus belongs to the RNA virus, there is a high mutation rate in the genome, and these mutations often locate on the Spike proteins of virus, the gripper of the virus entering the cells. Vaccination induce the generation of antibodies, which block Spike protein. However, the Spike protein variants may change the recognition and binding of antibodies and make the vaccine ineffective. In this study, we predict neutralizing antibody recognition sites (B cell epitopes) of the prototype S protein of SARS-COV2, along with several common variants using bioinformatics tools. We discovered the variability in antigenicity among the mutants, for instance, in the more widespread D614G variant the change of epitope was least affected, only with slight increase of antigenicity. However, the antigenic epitopes of some mutants change greatly. These results could be of potential importance for future vaccine design and application against SARS-CoV2 variants. url: https://doi.org/10.1101/2020.08.24.264895 doi: 10.1101/2020.08.24.264895 id: cord-286001-pu1fetq7 author: Zang, Ruochen title: TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes date: 2020-04-23 words: 2049.0 sentences: 145.0 pages: flesch: 50.0 cache: ./cache/cord-286001-pu1fetq7.txt txt: ./txt/cord-286001-pu1fetq7.txt summary: In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. Importantly, we found that 160 expression of TMPRSS4 but not ST14 also resulted in a significant increase in the levels of viral RNA and infectious virus titers in the presence of ACE2 ( Fig. 3B and S3C) . Collectively, we have shown that TMPRSS2 and TMPRSS4 activate SARS-CoV-2 S and 187 enhance membrane fusion and viral endocytosis into host cells. Importantly, abrogating TMPRSS4 expression led 209 to a 4-fold reduction in SARS-CoV-2 chimera virus replication in human enteroid, even 210 more significant than TMPRSS2 knockout (Fig. 4B) , highlighting its importance in 211 mediating virus replication in primary cells. It is possible that in the 293 small intestine, whereas SARS-CoV-2 is relatively stable, additional proteases such as 294 trypsin likely enhance viral pathogenesis by triggering more robust IEC fusion (Fig. S2A) . abstract: Both gastrointestinal symptoms and fecal shedding of SARS-CoV-2 RNA have been frequently observed in COVID-19 patients. However, whether SARS-CoV-2 replicate in the human intestine and its clinical relevance to potential fecal-oral transmission remain unclear. Here, we demonstrate productive infection of SARS-CoV-2 in ACE2+ mature enterocytes in human small intestinal enteroids. In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. However, newly synthesized viruses released into the intestinal lumen were rapidly inactivated by human colonic fluids and no infectious virus was recovered from the stool specimens of COVID-19 patients. Our results highlight the intestine as a potential site of SARS-CoV-2 replication, which may contribute to local and systemic illness and overall disease progression. url: https://doi.org/10.1101/2020.04.21.054015 doi: 10.1101/2020.04.21.054015 id: cord-103895-dt0ers70 author: Zeng, Xiangrui title: Comparative Pathway Integrator: a framework of meta-analytic integration of multiple transcriptomic studies for consensual and differential pathway analysis date: 2018-10-16 words: 4508.0 sentences: 269.0 pages: flesch: 54.0 cache: ./cache/cord-103895-dt0ers70.txt txt: ./txt/cord-103895-dt0ers70.txt summary: Methods and Results We present a meta-analytic integration tool, Comparative Pathway Integrator (CPI), to address these issues using adaptively weighted Fisher''s method to discover consensual and differential enrichment patterns, consensus clustering to reduce pathway redundancy, and a novel text mining algorithm to assist interpretation of the pathway clusters. In light of this, we proposed a framework of meta-analytical integration of multiple transcriptomic studies for consensual and differential pathway analysis, wrapped in a tool named Comparative Pathway Integrator (CPI). In order to identify both commonly and study-specifically enriched pathways, we applied the adaptively weighted Fisher''s method [14] , which is originally developed to combine p-values from multiple genomic studies for detecting homogeneous and heterogeneous differentially expressed genes. In summary, CPI is a meta-analytic tool for discovering commonly expressed and study specific pattern in transcriptomic studies, that will also reduce pathway redundancy and conduct text mining to increase interpretability of the results. abstract: Motivation Pathway analysis provides a knowledge-driven approach to interpret differentially expressed genes associated with disease status. Many tools have been developed to analyze a single study. When multiple studies of different conditions are jointly analyzed, novel integrative tools are needed. In addition, pathway redundancy issue introduced by combining public pathway databases hinders knowledge discovery. Methods and Results We present a meta-analytic integration tool, Comparative Pathway Integrator (CPI), to address these issues using adaptively weighted Fisher’s method to discover consensual and differential enrichment patterns, consensus clustering to reduce pathway redundancy, and a novel text mining algorithm to assist interpretation of the pathway clusters. We applied CPI to jointly analyze six psychiatric disorder transcriptomic studies to demonstrate its effectiveness, and found functions confirmed by previous biological studies as well novel enrichment patterns. Availability CPI is accessible online: http://tsenglab.biostat.pitt.edu/software.htm. Contact xiangruz@andrew.cmu.edu url: https://doi.org/10.1101/444604 doi: 10.1101/444604 id: cord-253447-4w6caxwu author: Zeng, Xin title: Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy date: 2020-04-20 words: 2866.0 sentences: 161.0 pages: flesch: 54.0 cache: ./cache/cord-253447-4w6caxwu.txt txt: ./txt/cord-253447-4w6caxwu.txt summary: title: Blocking antibodies against SARS-CoV-2 RBD isolated from a phage display antibody library using a competitive biopanning strategy SARS-CoV-2 relies on its spike protein, in particular the receptor binding domain (RBD), to bind human cell receptor angiotensin-converting enzyme 2 (ACE2) for viral entry, and thus targeting RBD holds the promise for preventing SARS-CoV-2 infection. In this work, a competitive biopanning strategy of a phage display antibody library was applied to screen blocking antibodies against RBD. It was proved to competitively block the binding of RBD to ACE2 protein, and potently inhibit SARS-CoV-2 pseudovirus infection of ACE2-overexpressing Hela cells with IC50 values of 12nM. Several high-affinity antibodies targeting SARS-CoV-2 RBD and blocking its binding to ACE2 were isolated, and the top 1 lead exhibited a neutralization activity of SARS-CoV-2 pseudotyped VSV infection. A high-affinity antibody against the target protein can be screened from a phage display antibody library using the standard biopanning process, but its binding epitopes are identified by some extra steps, such as epitope mapping and competitive ELISA. abstract: The infection of the novel coronavirus SARS-CoV-2 have caused more than 150,000 deaths, but no vaccine or specific therapeutic antibody is currently available. SARS-CoV-2 relies on its spike protein, in particular the receptor binding domain (RBD), to bind human cell receptor angiotensin-converting enzyme 2 (ACE2) for viral entry, and thus targeting RBD holds the promise for preventing SARS-CoV-2 infection. In this work, a competitive biopanning strategy of a phage display antibody library was applied to screen blocking antibodies against RBD. High-affinity antibodies were enriched after the first round using a standard panning process in which RBD-His recombinant protein was immobilized as a bait. At the next two rounds, immobilized ACE2-Fc and free RBD-His proteins were mixed with the enriched phage antibodies. Antibodies binding to RBD at epitopes different from ACE2-binding site were captured by the immobilized ACE2-Fc, forming a “sandwich” complex. Only antibodies competed with ACE2 for recognizing RBD at the same or similar epitopes can bind to the free RBD-His in the supernatant and be subsequently separated by the Ni-NTA magnetic beads. Top 1 lead from the competitive biopanning of a synthetic antibody library, Lib AB1, was produced as the full-length IgG1 format. It was proved to competitively block the binding of RBD to ACE2 protein, and potently inhibit SARS-CoV-2 pseudovirus infection of ACE2-overexpressing Hela cells with IC50 values of 12nM. Nevertheless, top 1 lead from the standard biopanning of Lib AB1, can only bind to RBD in vitro but not have the blocking or neutralization activity. Our strategy can efficiently isolate the blocking antibodies of RBD, and it would speed up the discovery of neutralizing antibodies against SARS-CoV-2. url: https://doi.org/10.1101/2020.04.19.049643 doi: 10.1101/2020.04.19.049643 id: cord-102631-a8fsr6ys author: Zeng, Zipeng title: Generation of kidney ureteric bud and collecting duct organoids that recapitulate kidney branching morphogenesis date: 2020-04-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Kidney organoids model development and diseases of the nephron but not the contiguous epithelial network of the kidney’s collecting duct (CD) system. Here, we report the generation of an expandable, 3D branching ureteric bud (UB) organoid culture model that can be derived from primary UB progenitors from mouse and human fetal kidneys, or generated de novo from pluripotent human stem cells. UB organoids differentiate into CD organoids in vitro, with differentiated cell types adopting spatial assemblies reflective of the adult kidney collecting system. Aggregating 3D-cultured nephron progenitor cells with UB organoids in vitro results in a reiterative process of branching morphogenesis and nephron induction, similar to kidney development. Combining efficient gene editing with the UB organoid model will facilitate an enhanced understanding of development, regeneration and diseases of the mammalian collecting system. One sentence summary Collecting duct organoids derived from primary mouse and human ureteric bud progenitor cells and human pluripotent stem cells provide an in vitro platform for genetic dissection of development, regeneration and diseases of the mammalian collecting system. url: https://doi.org/10.1101/2020.04.27.049031 doi: 10.1101/2020.04.27.049031 id: cord-308310-wtmjt3hf author: Zha, Lisha title: Development of a COVID-19 vaccine based on the receptor binding domain displayed on virus-like particles date: 2020-05-14 words: 2012.0 sentences: 110.0 pages: flesch: 54.0 cache: ./cache/cord-308310-wtmjt3hf.txt txt: ./txt/cord-308310-wtmjt3hf.txt summary: Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro. The receptor binding domain (RBD) of the SARS spike protein binds to ACE2 and is an important target for neutralizing antibodies [5] [6] [7] . Hence, the RBD-CuMVTT vaccine candidate is able to induce high levels of SARS-CoV-2 neutralizing antibodies. Receptor-binding domain of SARS-CoV spike protein induces highly potent neutralizing antibodies: implication for developing subunit vaccine abstract: The recently ermerging disease COVID-19 is caused by the new SARS-CoV-2 virus first detected in the city of Wuhan, China. From there it has been rapidly spreading inside and outside China. With initial death rates around 4%, COVID-19 patients at longer distances from Wuhan showed reduced mortality as was previously observed for the SARS coronavirus. However, the new coronavirus spreads more strongly, as it sheds long before onset of symptoms or may be transmitted by people without symptoms. Rapid development of a protective vaccine against COVID-19 is therefore of paramount importance. Here we demonstrate that recombinantly expressed receptor binding domain (RBD) of the spike protein homologous to SARS binds to ACE2, the viral receptor. Higly repetitive display of RBD on immunologically optimized virus-like particles derived from cucumber mosaic virus resulted in a vaccine candidate (RBD-CuMVTT) that induced high levels of specific antibodies in mice which were able to block binding of spike protein to ACE2 and potently neutralized the SARS-CoV-2 virus in vitro. url: https://doi.org/10.1101/2020.05.06.079830 doi: 10.1101/2020.05.06.079830 id: cord-104162-fe51v2pt author: Zhang, Chiyu title: Potential Achilles heels of SARS-CoV-2 displayed by the base order-dependent component of RNA folding energy date: 2020-11-02 words: 3745.0 sentences: 208.0 pages: flesch: 49.0 cache: ./cache/cord-104162-fe51v2pt.txt txt: ./txt/cord-104162-fe51v2pt.txt summary: Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions – such as the ribosomal frameshifting element (FSE) that facilitates differential expression of 1a and 1ab polyproteins – can be considered potential "Achilles heels" for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. Assays of the base order-dependent component of the folding energy have shown that a highly conserved region, in otherwise rapidly mutating HIV-1 genomes, associates with an RNA structure corresponding, not to a protein-encoding function, but to an RNA packaging signal. This high GC% value can obscure the contribution of the base order-dependent component of the folding energy, which provides a sensitive indicator of local intraspecies pressures for the conservation of function within a population (i.e. a mutated organism is eliminated by natural selection so no longer can be assayed for function in the population). abstract: Base order, not composition, best reflects local evolutionary pressure for folding of single-stranded nucleic acids. The base order-dependent component of folding energy has revealed a highly conserved region in HIV-1 genomes that associates with RNA structure. This corresponds to a packaging signal that is recognized by the nucleocapsid domain of the Gag polyprotein. Long viewed as a potential HIV-1 “Achilles heel,” the signal can be targeted by a recently described antiviral compound (NSC 260594) or by synthetic oligonucleotides. Thus, a conserved base-order-rich region of HIV-1 may facilitate therapeutic attack. Although SARS-CoV-2 differs in many respects from HIV-1, the same technology displays regions with a high base order-dependent folding energy component, which are also highly conserved. This indicates structural invariance (SI) sustained by natural selection. While the regions are often also protein-encoding (e.g. NSP3, ORF3a), we suggest that their nucleic acid level functions – such as the ribosomal frameshifting element (FSE) that facilitates differential expression of 1a and 1ab polyproteins – can be considered potential “Achilles heels” for SARS-CoV-2, perhaps susceptible to therapies like those envisaged for AIDS. The region of the FSE scored well, but higher SI scores were obtained in other regions, including those encoding NSP13 and the nucleocapsid (N) protein. url: https://doi.org/10.1101/2020.10.22.343673 doi: 10.1101/2020.10.22.343673 id: cord-103709-86hv27vh author: Zhang, Dong Yan title: Prefusion spike protein stabilization through computational mutagenesis date: 2020-06-19 words: 3243.0 sentences: 184.0 pages: flesch: 53.0 cache: ./cache/cord-103709-86hv27vh.txt txt: ./txt/cord-103709-86hv27vh.txt summary: The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We subject the selected residues to computational redesign using Eris to find the stabilizing mutations by calculating the change in free energy ∆∆ = ∆ − ∆ , where ∆ and ∆ are the free energies of the mutant protein and wild type proteins correspondingly. After the designation of the mutation sites, the pipeline utilizes Eris to determine the changes in free energies of the mutants. We analyze the conservation score, RMSF, and SASA of residues in the spike protein through the pipeline. Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes abstract: A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines’ developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants. url: https://doi.org/10.1101/2020.06.17.157081 doi: 10.1101/2020.06.17.157081 id: cord-325348-yi6yu5l1 author: Zhang, G. title: Investigation of ACE2 N-terminal fragments binding to SARS-CoV-2 Spike RBD date: 2020-06-17 words: 2664.0 sentences: 160.0 pages: flesch: 54.0 cache: ./cache/cord-325348-yi6yu5l1.txt txt: ./txt/cord-325348-yi6yu5l1.txt summary: Recent cryo-electron microscopy (cryo-EM) structural studies of the SARS-CoV-2 spike protein 68 receptor binding domain (RBD) in complex with full-length human ACE2 receptor revealed key 69 amino acid residues at the contact interface between the two proteins and estimated the binding 70 affinity at ~15 nM [7, 8] . The results of this MD simulation suggest 108 that SBP1 and SBP2 peptides derived from the ACE-PD α1 helix may alone potentially bind the 109 SARS-CoV-2 spike RBD protein with sufficient affinity to disrupt the associated PPI. However, competition was not observed when using non-biotinylated SBP1 pre-140 mixed in solution with Sino Biological insect-derived SARS-CoV-2-RBD, even with a 1000-fold 141 excess of the peptide (Fig. 3C, 3E ). In conclusion, a biotinylated peptide sequence derived from human ACE2 was found to 205 bind Sino Biological insect-derived SARS-CoV-2 spike protein RBD with micromolar affinity, but 206 did not associate with SARS-CoV-2-RBD variants obtained from other commercial sources. abstract: Coronavirus disease 19 (COVID-19) is an emerging global health crisis. With over 7 million confirmed cases to date, this pandemic continues to expand, spurring research to discover vaccines and therapies. SARS-CoV-2 is the novel coronavirus responsible for this disease. It initiates entry into human cells by binding to angiotensin-converting enzyme 2 (ACE2) via the receptor binding domain (RBD) of its spike protein (S). Disrupting the SARS-CoV-2-RBD binding to ACE2 with designer drugs has the potential to inhibit the virus from entering human cells, presenting a new modality for therapeutic intervention. Peptide-based binders are an attractive solution to inhibit the RBD-ACE2 interaction by adequately covering the extended protein contact interface. Using molecular dynamics simulations based on the recently solved cryo-EM structure of ACE2 in complex with SARS-CoV-2-RBD, we observed that the ACE2 peptidase domain (PD) α1 helix is important for binding SARS-CoV-2-RBD. Using automated fast-flow peptide synthesis, we chemically synthesized a 23-mer peptide fragment of the ACE2 PD α1 helix (SBP1) composed entirely of proteinogenic amino acids. Chemical synthesis of SBP1 was complete in 1.5 hours, and after work up and isolation >20 milligrams of pure material was obtained. Bio-layer interferometry (BLI) revealed that SBP1 associates with micromolar affinity to insect-derived SARS-CoV-2-RBD protein obtained from Sino Biological. Association of SBP1 was not observed to an appreciable extent to HEK cell-expressed SARS-CoV-2-RBD proteins and insect-derived variants acquired from other vendors. Moreover, competitive BLI assays showed SBP1 does not outcompete ACE2 binding to Sino Biological insect-derived SARS-CoV-2-RBD. Further investigations are ongoing to gain insight into the molecular and structural determinants of the variable binding behavior to different SARS-CoV-2-RBD protein variants. url: https://doi.org/10.1101/2020.03.19.999318 doi: 10.1101/2020.03.19.999318 id: cord-321155-dty18esg author: Zhang, Rongxin title: Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2 date: 2020-06-05 words: 4927.0 sentences: 331.0 pages: flesch: 57.0 cache: ./cache/cord-321155-dty18esg.txt txt: ./txt/cord-321155-dty18esg.txt summary: We also found that the SUD-like sequence is retained in the SARS-CoV-2 genome, while some other coronaviruses that can infect humans are depleted. To get the potential G-quadruplexes in the SARS-CoV-2 genome, we took the strategy described as follows ( Fig. 2A) : (i) Predicting the PG4s with three software independently. To further characterize the potential canonical secondary structures competitive with Gquadruplexes, the landscape of thermodynamic stability of the SARS-CoV-2 genome was depicted by using ΔG°z-score [55] . The distributions of loop length between the SARS-CoV-2 PG4s and the human two-quartet Gquadruplexes did not show discrepancies (Fig. S1 , Wilcoxon test, p-value = 0.4552). Recent research revealed that the G-quadruplexes in human UTRs (Untranslated Regions) are under selective pressures [58] , and some coronaviruses on bats and pangolins are closely related to SARS-CoV-2. Thus, we started to explore whether the SARS-CoV-2 genome contains the protein-coding sequence similar to SUD and whether SARS-CoV-2 retains the ability to bind RNA G-quadruplexes. abstract: The Coronavirus Disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) quickly become a global public health emergency. G-quadruplex, one of the non-canonical secondary structures, has shown potential antiviral values. However, little is known about G-quadruplexes on the emerging SARS-CoV-2. Herein, we characterized the potential G-quadruplexes both in the positive and negative-sense viral stands. The identified potential G-quadruplexes exhibits similar features to the G-quadruplexes detected in the human transcriptome. Within some bat and pangolin related beta coronaviruses, the G-quartets rather than the loops are under heightened selective constraints. We also found that the SUD-like sequence is retained in the SARS-CoV-2 genome, while some other coronaviruses that can infect humans are depleted. Further analysis revealed that the SARS-CoV-2 SUD-like sequence is almost conserved among 16,466 SARS-CoV-2 samples. And the SARS-CoV-2 SUDcore-like dimer displayed similar electrostatic potential pattern to the SUD dimer. Considering the potential value of G-quadruplexes to serve as targets in antiviral strategy, we hope our fundamental research could provide new insights for the SARS-CoV-2 drug discovery. url: https://doi.org/10.1101/2020.06.05.135749 doi: 10.1101/2020.06.05.135749 id: cord-332185-a96r1k7a author: Zhang, Shuyuan title: Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution date: 2020-09-22 words: 1228.0 sentences: 103.0 pages: flesch: 63.0 cache: ./cache/cord-332185-a96r1k7a.txt txt: ./txt/cord-332185-a96r1k7a.txt summary: title: Bat and pangolin coronavirus spike glycoprotein structures provide insights into SARS-CoV-2 evolution Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. Cryo-electron microscopy structures of the SARS-CoV spike 464 glycoprotein reveal a prerequisite conformational state for receptor binding Cryo-EM structure of the SARS 467 coronavirus spike glycoprotein in complex with its host cell receptor ACE2 Cryo-EM structures of MERS-CoV and SARS-CoV spike 495 glycoproteins reveal the dynamic receptor binding domains abstract: In recognizing the host cellular receptor and mediating fusion of virus and cell membranes, the spike (S) glycoprotein of coronaviruses is the most critical viral protein for cross-species transmission and infection. Here we determined the cryo-EM structures of the spikes from bat (RaTG13) and pangolin (PCoV_GX) coronaviruses, which are closely related to SARS-CoV-2. All three receptor-binding domains (RBDs) of these two spike trimers are in the “down” conformation, indicating they are more prone to adopt this receptor-binding inactive state. However, we found that the PCoV_GX, but not the RaTG13, spike is comparable to the SARS-CoV-2 spike in binding the human ACE2 receptor and supporting pseudovirus cell entry. Through structure and sequence comparisons, we identified critical residues in the RBD that underlie the different activities of the RaTG13 and PCoV_GX/SARS-CoV-2 spikes and propose that N-linked glycans serve as conformational control elements of the RBD. These results collectively indicate that strong RBD-ACE2 binding and efficient RBD conformational sampling are required for the evolution of SARS-CoV-2 to gain highly efficient infection. url: https://doi.org/10.1101/2020.09.21.307439 doi: 10.1101/2020.09.21.307439 id: cord-328187-9zd79gai author: Zhang, Yali title: Virus-free and live-cell visualizing SARS-CoV-2 cell entry for studies of neutralizing antibodies and compound inhibitors date: 2020-07-22 words: 3018.0 sentences: 165.0 pages: flesch: 55.0 cache: ./cache/cord-328187-9zd79gai.txt txt: ./txt/cord-328187-9zd79gai.txt summary: The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. 22 On 293T-ACE2iRb3 cells, both the SARS-CoV2-RBG and SARS-CoV2-STG 23 probes showed effective-binding to the cells, as membrane-bound and hACE2-24 mRuby3-colocalized mGam signals were observed after a 6-min incubation with the 25 cells ( Figure 2C ). Compared with 3 samples from healthy donors (n=40), all COVID-19-convalescent plasmas showed 4 significant cMFI inhibition on CSBT assay, whereas only 12 samples (37.5%) had 5 detectable CRBT activity ( Figure 3A ). Among the antibody titers derived from various assays, the 10 CSBT titer showed the best correlation with LVppNAT ( Figure 3D and Table S2, 11 r=0.832, p<0.001), and it also well correlated (r=0.959, p<0.001, Figure 3D ) with the 12 neutralization activity against authentic SARS-CoV-2 virus in 12 representative 13 samples (Table S3) . abstract: The ongoing COVID-19 pandemic, caused by SARS-CoV-2 infection, has resulted in hundreds of thousands of deaths. Cellular entry of SARS-CoV-2, which is mediated by the viral spike protein and host ACE2 receptor, is an essential target for the development of vaccines, therapeutic antibodies, and drugs. Using a mammalian cell expression system, we generated a recombinant fluorescent protein (Gamillus)-fused SARS-CoV-2 spike trimer (STG) to probe the viral entry process. In ACE2-expressing cells, we found that the STG probe has excellent performance in the live-cell visualization of receptor binding, cellular uptake, and intracellular trafficking of SARS-CoV-2 under virus-free conditions. The new system allows quantitative analyses of the inhibition potentials and detailed influence of COVID-19-convalescent human plasmas, neutralizing antibodies and compounds, providing a versatile tool for high-throughput screening and phenotypic characterization of SARS-CoV-2 entry inhibitors. This approach may also be adapted to develop a viral entry visualization system for other viruses. url: https://doi.org/10.1101/2020.07.22.215236 doi: 10.1101/2020.07.22.215236 id: cord-102763-tc1z0nm9 author: Zhang, Yuan title: IgY antibodies against Ebola virus possess post-exposure protection and excellent thermostability date: 2020-05-21 words: 1764.0 sentences: 104.0 pages: flesch: 53.0 cache: ./cache/cord-102763-tc1z0nm9.txt txt: ./txt/cord-102763-tc1z0nm9.txt summary: Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. We developed a highly thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The newborn mice receiving passive transfer of IgY achieved complete protection against a lethal dose of virus challenge indicating that the anti-EBOV IgY provides a promising countermeasure to solve the current clinical application problems of Ebola antibody-based treatments in Africa. To obtain high titer EBOV NAbs, 5-month-old laying hens were vaccinated with five different 124 immunogens, including 10 3 or 10 4 TCID 50 VSVΔ G/EBOVGP, 100 μ g rEBOVGP, 100 μ g 125 pCAGGS/EBOVGP, 10 μg EBOV-VLP, and 10 11 virus particles (vp) Ad5/EBOVGP (Fig 2a) . Protective 546 monotherapy against lethal Ebola virus infection by a potently neutralizing antibody Protective 546 monotherapy against lethal Ebola virus infection by a potently neutralizing antibody abstract: Ebola virus (EBOV) is the most virulent pathogens that cause hemorrhagic fever with high mortality rates in humans and nonhuman primates. The postexposure antibody therapies to prevent EBOV infection are considered efficient. However, due to the poor thermal stability of mammalian antibody, their application in the tropics has been limited. Here, we developed a thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25°C for one year, in contrast to conventional polyclonal or monoclonal antibodies (MAbs). We immunized laying hens with a variety of EBOV vaccine candidates and confirmed that VSV Δ G/EBOVGP encoding the EBOV glycoprotein could induce high titer neutralizing antibodies against EBOV. The therapeutic efficacy of immune IgY antibodies in vivo was evaluated in the newborn Balb/c mice model. Lethal dose of virus challenged mice were treated 2 or 24 h post-infection with different doses of anti-EBOV IgY. The group receiving a high dose of 106 NAU/kg (neutralizing antibody units/kilogram) achieved complete protection with no signs of disease, while the low-dose group was only partially protected. In contrast, all mice receiving naïve IgY died within 10 days. In conclusion, the anti-EBOV IgY exhibits excellent thermostability and protective efficacy, and it is very promising to be developed as alternative therapeutic entities. Author Summary Although several Ebola virus therapeutic antibodies have been reported in recent years, however, due to the poor thermal stability of mammalian antibody, their application in tropical endemic areas has been limited. We developed a highly thermostable therapeutic antibody against EBOV based on chicken immunoglobulin Y (IgY). The IgY antibodies demonstrated excellent thermal stability, which retained their neutralizing activity at 25°C for one year. The newborn mice receiving passive transfer of IgY achieved complete protection against a lethal dose of virus challenge indicating that the anti-EBOV IgY provides a promising countermeasure to solve the current clinical application problems of Ebola antibody-based treatments in Africa. url: https://doi.org/10.1101/2020.05.21.108159 doi: 10.1101/2020.05.21.108159 id: cord-103504-ucqqpra5 author: Zhang, Zhe title: The conserved ER-transmembrane protein TMEM39 coordinates with COPII to promote collagen secretion and prevent ER stress date: 2020-09-20 words: 2877.0 sentences: 184.0 pages: flesch: 55.0 cache: ./cache/cord-103504-ucqqpra5.txt txt: ./txt/cord-103504-ucqqpra5.txt summary: From a genome-wide RNAi screen for 54 genes affecting ER stress response, we previously identified tmem-131 that defines a 55 broadly conserved family of proteins important for procollagen assembly and secretion 56 (22). RNAi knock-down of sec-23 and most other COPII genes 340 recapitulated the tmem-39 loss-of-function phenotypes in constitutively high ER stress 341 response, defective collagen secretion and sensitivity to osmolality stress in C. We also noticed that RNAi knock-down of many COPII related genes, such 343 as sec-23, sec-24.1, npp-20, sar-1, sec-12, rab-5 and trpp-8 caused more severe 344 phenotypes than tmem-39 RNAi, leading to lethality or developmental arrest that 345 prevent collagen phenotype analysis (Table 1) Recent work showed that TMEM39A facilitates the ER-to-Golgi transport of SAC1 and 355 regulates autophagosome formation (28). We found that RNAi knock-down of 356 autophagy related genes, such as sac-1 and let-363, caused autophagy induction but 357 did not affect the ER stress response or collagen secretion (Fig 6) . abstract: Dysregulation of collagen production and secretion contributes to aging and tissue fibrosis of major organs. How premature collagen proteins in the endoplasmic reticulum (ER) route as specialized cargos for secretion remains to be fully elucidated. Here, we report that TMEM39, an ER-localized transmembrane protein, regulates production and secretory cargo trafficking of procollagen. We identify the C. elegans ortholog TMEM-39 from an unbiased RNAi screen and show that deficiency of tmem-39 leads to striking defects in cuticle collagen production and constitutively high ER stress response. RNAi knockdown of the tmem-39 ortholog in Drosophila causes similar defects in collagen secretion from fat body cells. The cytosolic domain of human TMEM39A binds to Sec23A, a vesicle coat protein that drives collagen secretion and vesicular trafficking. TMEM-39 regulation of collagen secretion is independent of ER stress response and autophagy. We propose that roles of TMEM-39 in collagen secretion and preventing ER stress are likely evolutionarily conserved. url: https://doi.org/10.1101/2020.08.17.253450 doi: 10.1101/2020.08.17.253450 id: cord-353554-98uzivsk author: Zhang, Zheng title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors date: 2018-03-08 words: 2190.0 sentences: 122.0 pages: flesch: 56.0 cache: ./cache/cord-353554-98uzivsk.txt txt: ./txt/cord-353554-98uzivsk.txt summary: title: Membrane proteins with high N-glycosylation, high expression, and multiple interaction partners were preferred by mammalian viruses as receptors Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. 64 The virus-receptor interaction was reported to be a principal determinant of viral host 65 range, tissue tropism and cross-species infection [11, 16, 22] . However, we found the viral receptor tended not to interact with each 248 other ( Figure S3D 270 Since the virus has to compete with other proteins for binding to the receptor, proteins (Table S5) . abstract: Receptor mediated entry is the first step for viral infection. However, the relationship between viruses and receptors is still obscure. Here, by manually curating a high-quality database of 268 pairs of mammalian virus-host receptor interaction, which included 128 unique viral species or sub-species and 119 virus receptors, we found the viral receptors were structurally and functionally diverse, yet they had several common features when compared to other cell membrane proteins: more protein domains, higher level of N-glycosylation, higher ratio of self-interaction and more interaction partners, and higher expression in most tissues of the host. Additionally, the receptors used by the same virus tended to co-evolve. Further correlation analysis between viral receptors and the tissue and host specificity of the virus shows that the virus receptor similarity was a significant predictor for mammalian virus cross-species. This work could deepen our understanding towards the viral receptor selection and help evaluate the risk of viral zoonotic diseases. url: https://doi.org/10.1101/271171 doi: 10.1101/271171 id: cord-324344-dxuabscn author: Zhao, Xuesen title: LY6E Restricts the Entry of Human Coronaviruses, including the currently pandemic SARS-CoV-2 date: 2020-04-05 words: 3152.0 sentences: 186.0 pages: flesch: 48.0 cache: ./cache/cord-324344-dxuabscn.txt txt: ./txt/cord-324344-dxuabscn.txt summary: In an effort to search for the host cellular protein(s) mediating the differential 29 susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and 30 LY6E, three cellular proteins with known activity of interfering virus entry, expressed at 31 significantly higher levels in HepG2 cells. In an effort to search for the host cellular protein(s) mediating the differential 29 susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and 30 LY6E, three cellular proteins with known activity of interfering virus entry, expressed at 31 significantly higher levels in HepG2 cells. Finally, the findings that LY6E inhibits human CoV entry cannot be evaded by ectopic 284 expression of membrane-associated serine protease TMPRSS2 and compromised by AmphoB 285 treatment strongly indicate that LY6E modulates virus entry via a distinct mechanism from that 286 IFITM proteins do (Figs. abstract: C3A is a sub-clone of human hepatoblastoma HepG2 cell line with the strong contact inhibition of growth. We fortuitously found that C3A was more susceptible to human coronavirus HCoV-OC43 infection than HepG2, which was attributed to the increased efficiency of virus entry into C3A cells. In an effort to search for the host cellular protein(s) mediating the differential susceptibility of the two cell lines to HCoV-OC43 infection, we found that ADAP2, GILT and LY6E, three cellular proteins with known activity of interfering virus entry, expressed at significantly higher levels in HepG2 cells. Functional analyses revealed that ectopic expression of LY6E, but not GILT or ADAP2, in HEK 293 cells inhibited the entry of HCoV-OC43. While overexpression of LY6E in C3A and A549 cells efficiently inhibited the infection of HCoV-OC43, knockdown of LY6E expression in HepG2 significantly increased its susceptibility to HCoV-OC43 infection. Moreover, we found that LY6E also efficiently restricted the entry mediated by the envelope spike proteins of other human coronaviruses, including the currently pandemic SARS-CoV-2. Interestingly, overexpression of serine protease TMPRSS2 or amphotericin treatment significantly neutralized the IFITM3 restriction of human coronavirus entry, but did not compromise the effect of LY6E on the entry of human coronaviruses. The work reported herein thus demonstrates that LY6E is a critical antiviral immune effector that controls CoV infection and pathogenesis via a distinct mechanism. Importance Virus entry into host cells is one of the key determinants of host range and cell tropism and is subjected to the control by host innate and adaptive immune responses. In the last decade, several interferon inducible cellular proteins, including IFITMs, GILT, ADAP2, 25CH and LY6E, had been identified to modulate the infectious entry of a variety of viruses. Particularly, LY6E was recently identified as host factors to facilitate the entry of several human pathogenic viruses, including human immunodeficiency virus, influenza A virus and yellow fever virus. Identification of LY6E as a potent restriction factor of coronaviruses expands the biological function of LY6E and sheds new light on the immunopathogenesis of human coronavirus infection. url: https://doi.org/10.1101/2020.04.02.021469 doi: 10.1101/2020.04.02.021469 id: cord-350627-4pgish5x author: Zhao, Yu title: Single-cell RNA expression profiling of ACE2,thereceptor of SARS-CoV-2 date: 2020-01-26 words: 1865.0 sentences: 129.0 pages: flesch: 56.0 cache: ./cache/cord-350627-4pgish5x.txt txt: ./txt/cord-350627-4pgish5x.txt summary: Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. These studies showed that in normal human lung, ACE2 is mainly expressed by type II and type I alveolar epithelial cells. In total, we analyzed 43,134 cells derived from normal lung tissue of To further understand the special population of ACE2-expressing AT2, we performed gene ontology enrichment analysis to study which biological processes are involved with this cell population by comparing them with the AT2 cells not expressing ACE2. Of note, the 2 male donors have a higher ACE2-expressing cell ratio than all other 6 female author/funder. We also noticed that the only Asian donor (male) has a much higher ACE2Altogether, in the current study, we report the RNA expression profile of ACE2 in the human lung at single-cell resolution. https://doi.org/10.1101/2020.01.26.919985 doi: bioRxiv preprint author/funder. abstract: A novel coronavirus SARS-CoV-2 was identified in Wuhan, Hubei Province, China in December of 2019. According to WHO report, this new coronavirus has resulted in 76,392 confirmed infections and 2,348 deaths in China by 22 February, 2020, with additional patients being identified in a rapidly growing number internationally. SARS-CoV-2 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral entry, reproduction and transmission. This study provides a biological background for the epidemic investigation of the COVID-19, and could be informative for future anti-ACE2 therapeutic strategy development. url: https://doi.org/10.1101/2020.01.26.919985 doi: 10.1101/2020.01.26.919985 id: cord-339720-d1stzy8w author: Zhao, Yuan title: Susceptibility of tree shrew to SARS-CoV-2 infection date: 2020-04-30 words: 2572.0 sentences: 180.0 pages: flesch: 58.0 cache: ./cache/cord-339720-d1stzy8w.txt txt: ./txt/cord-339720-d1stzy8w.txt summary: No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature (above 39° C) particular in female animals during infection. In three young tree shrews (TS26, TS27 and TS28), we could detect viral RNA from only lungs in TS26 and TS27, but not in any tissue from TS28, although these animal had higher number of viral genomic copy numbers at the earlier stage of SARS-CoV-2 infection. Although SARS-CoV-2 infection didn''t cause severe disease in all three ages of tree shrews, viral replication and mild histopathological changes were still observed in this study. In conclusion, tree shrew is not as susceptible to SARS-CoV-2 infection as the reported animal models of COVID-19, though limited replication of SARS-CoV-2 and mild histopathology was detected and observed in some tissues. Young Old Adult 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 Histopathological examination of affected tissues from SARS-CoV-2 infected tree shrews. abstract: Since SARS-CoV-2 became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and COVID-19 were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature (above 39° C) particular in female animals during infection. Low levels of virus shedding and replication in tissues occurred in all three age groups, each of which showed his own characteristics. Histopathological examine revealed that pulmonary abnormalities were mild but the main changes although slight lesions were also observed in other tissues. In summary, tree shrew is not susceptible to SARS-CoV-2 infection and may not be a suitable animal for COVID-19 related researches. url: https://doi.org/10.1101/2020.04.30.029736 doi: 10.1101/2020.04.30.029736 id: cord-271693-7tg21up3 author: Zheng, Fan title: Identifying persistent structures in multiscale ‘omics data date: 2020-10-03 words: 4889.0 sentences: 291.0 pages: flesch: 48.0 cache: ./cache/cord-271693-7tg21up3.txt txt: ./txt/cord-271693-7tg21up3.txt summary: Many different approaches have been devised or applied to detect structures in biological data, including standard clustering, network community detection, and low-dimensional data projection [5] [6] [7] , some of which can be tuned for sensitivity to objects of a certain size or scale (so-called ''resolution parameters'') [8, 9] . We first explored the idea of measuring community persistence via analysis of synthetic datasets [15] in which communities were simulated and embedded in the similarity network at two different scales (Supplementary Fig. 1a; Methods) . Application to protein-protein interaction networks from budding yeast and human found that HiDeF captured knowledge in GO more significantly than previous pipelines proposed for this task, including the NeXO approach to hierarchical community detection [23] and standard hierarchical clustering of pairwise protein distances calculated by three recent network embedding approaches [24] [25] [26] (Fig. 3a, Fig. 7) . abstract: In any ‘omics study, the scale of analysis can dramatically affect the outcome. For instance, when clustering single-cell transcriptomes, is the analysis tuned to discover broad or specific cell types? Likewise, protein communities revealed from protein networks can vary widely in sizes depending on the method. Here we use the concept of “persistent homology”, drawn from mathematical topology, to identify robust structures in data at all scales simultaneously. Application to mouse single-cell transcriptomes significantly expands the catalog of identified cell types, while analysis of SARS-COV-2 protein interactions suggests hijacking of WNT. The method, HiDeF, is available via Python and Cytoscape. url: https://www.ncbi.nlm.nih.gov/pubmed/32587977/ doi: 10.1101/2020.06.16.151555 id: cord-282795-kje7rn57 author: Zheng, Yue title: Neutralization Assay with SARS-CoV-1 and SARS-CoV-2 Spike Pseudotyped Murine Leukemia Virions date: 2020-09-21 words: 487.0 sentences: 36.0 pages: flesch: 58.0 cache: ./cache/cord-282795-kje7rn57.txt txt: ./txt/cord-282795-kje7rn57.txt summary: To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. Pseudotyped MLV viruses were tested on HEK293FT, HEK293T-ACE2, Huh7 and SupT1 cells. To test for specificity of neutralization, we asked whether neutralizing antibodies from SARSCoV-2 patients would exhibit cross-reactivity against a pseudotype expressing SARS-CoV-1 ( Figure 112 4). Characterization of 162 spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with 163 SARS-CoV Veesler D: Structure, Function, and 165 Antigenicity of the SARS-CoV-2 Spike Glycoprotein The 167 D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases 168 infectivity High-efficiency gene 170 transfer into CD34+ cells with a human immunodeficiency virus type 1-based retroviral 171 vector pseudotyped with vesicular stomatitis virus envelope glycoprotein G Pseudotyping Viral Vectors With Emerging Virus Envelope 177 Proteins abstract: Antibody neutralization is an important prognostic factor in many viral diseases. To easily and rapidly measure titers of neutralizing antibodies in serum or plasma, we developed pseudovirion particles composed of the spike glycoprotein of SARS-CoV-2 incorporated onto murine leukemia virus capsids and a modified minimal MLV genome encoding firefly luciferase. These pseudovirions provide a practical means of assessing immune responses under laboratory conditions consistent with biocontainment level 2. url: https://www.ncbi.nlm.nih.gov/pubmed/32995778/ doi: 10.1101/2020.07.17.207563 id: cord-327711-welf0eb1 author: Zhou, Daming title: Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient date: 2020-06-13 words: 4847.0 sentences: 290.0 pages: flesch: 59.0 cache: ./cache/cord-327711-welf0eb1.txt txt: ./txt/cord-327711-welf0eb1.txt summary: Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19. A neutralisation test for EY6A based on quantitative PCR detection of virus in the supernatant bathing infected Vero E6 cells after 5 days of culture, showed a ~1000-fold reduction in virus signal (Methods, Extended Data Fig. 3 ) indicating that it is highly neutralising. To elucidate the epitope of EY6A, we determined the crystal structures of the deglycosylated SARS-CoV-2 RBD in complex with EY6A Fab alone and in a ternary complex incorporating a nanobody (Nb) which has been shown to compete with ACE2 (for data on a closely related Nb see Huo 2020, submitted), as a crystallisation chaperone. abstract: The COVID-19 pandemic has had unprecedented health and economic impact, but currently there are no approved therapies. We have isolated an antibody, EY6A, from a late-stage COVID-19 patient and show it neutralises SARS-CoV-2 and cross-reacts with SARS-CoV-1. EY6A Fab binds tightly (KD of 2 nM) the receptor binding domain (RBD) of the viral Spike glycoprotein and a 2.6Å crystal structure of an RBD/EY6A Fab complex identifies the highly conserved epitope, away from the ACE2 receptor binding site. Residues of this epitope are key to stabilising the pre-fusion Spike. Cryo-EM analyses of the pre-fusion Spike incubated with EY6A Fab reveal a complex of the intact trimer with three Fabs bound and two further multimeric forms comprising destabilized Spike attached to Fab. EY6A binds what is probably a major neutralising epitope, making it a candidate therapeutic for COVID-19. url: https://doi.org/10.1101/2020.06.12.148387 doi: 10.1101/2020.06.12.148387 id: cord-333420-qqyg9um9 author: Zhu, Xun title: idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates date: 2020-10-09 words: 460.0 sentences: 35.0 pages: flesch: 58.0 cache: ./cache/cord-333420-qqyg9um9.txt txt: ./txt/cord-333420-qqyg9um9.txt summary: title: idCOV: a pipeline for quick clade identification of SARS-CoV-2 isolates idCOV is a phylogenetic pipeline for quickly identifying the clades of SARS-CoV-2 virus isolates from raw sequencing data based on a selected clade-defining marker list. Using a public dataset, we show that idCOV can make equivalent calls as annotated by Nextstrain.org on all three common clade systems using user uploaded FastQ files directly. The on-going Coronavirus disease 2019 (Covid-19) pandemic has resulted in over 734,000 deaths, affect-20 ing more than 188 countries and territories (CSSE, 2020; Dong, et al., 2020) . Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously known as 2019-nCoV) 23 is the pathogenic cause of Covid-19 (Lescure, et al., 2020) . In order to quickly identify the clade of an isolate of SARS-Cov-2 given its sequencing FastQ files, 30 we have developed a bioinformatics pipeline and a user-friendly web interface. abstract: idCOV is a phylogenetic pipeline for quickly identifying the clades of SARS-CoV-2 virus isolates from raw sequencing data based on a selected clade-defining marker list. Using a public dataset, we show that idCOV can make equivalent calls as annotated by Nextstrain.org on all three common clade systems using user uploaded FastQ files directly. Web and equivalent command-line interfaces are available. It can be deployed on any Linux environment, including personal computer, HPC and the cloud. The source code is available at https://github.com/xz-stjude/idcov. A documentation for installation can be found at https://github.com/xz-stjude/idcov/blob/master/README.md. url: https://doi.org/10.1101/2020.10.08.330456 doi: 10.1101/2020.10.08.330456 id: cord-307504-cogk5kig author: Zhu, Yuanmei title: Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity date: 2020-03-28 words: 1946.0 sentences: 107.0 pages: flesch: 51.0 cache: ./cache/cord-307504-cogk5kig.txt txt: ./txt/cord-307504-cogk5kig.txt summary: title: Design of potent membrane fusion inhibitors against SARS-CoV-2, an emerging coronavirus with high fusogenic activity In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity. Then, we designed a HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly poent activities in inibibiting the SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus infection. Taken together, these results suggested that 128 SARS-CoV-2 might evolve an increased interaction between the HR1 and HR2 domains in 129 the S2 fusion protein thus critically determining its high fusogenic activity. Interaction between heptad repeat 1 and 2 regions in spike protein of SARS-associated coronavirus: 354 implications for virus fusogenic mechanism and identification of fusion inhibitors Severe acute respiratory syndrome coronavirus (SARS-CoV) infection inhibition 368 using spike protein heptad repeat-derived peptides Heptad repeat-derived peptides block protease-mediated direct entry from the cell surface of 371 severe acute respiratory syndrome coronavirus but not entry via the endosomal pathway abstract: The coronavirus disease COVID-19, caused by emerging SARS-CoV-2, has posed serious threats to global public health, economic and social stabilities, calling for the prompt development of therapeutics and prophylactics. In this study, we firstly verified that SARS-CoV-2 uses human ACE2 as a cell receptor and its spike (S) protein mediates high membrane fusion activity. Comparing to that of SARS-CoV, the heptad repeat 1 (HR1) sequence in the S2 fusion protein of SARS-CoV-2 possesses markedly increased α-helicity and thermostability, as well as a higher binding affinity with its corresponding heptad repeat 2 (HR1) site. Then, we designed a HR2 sequence-based lipopeptide fusion inhibitor, termed IPB02, which showed highly poent activities in inibibiting the SARS-CoV-2 S protein-mediated cell-cell fusion and pseudovirus infection. IPB02 also inhibited the SARS-CoV pseudovirus efficiently. Moreover, the strcuture and activity relationship (SAR) of IPB02 were characterzized with a panel of truncated lipopeptides, revealing the amino acid motifs critical for its binding and antiviral capacities. Therefore, the presented results have provided important information for understanding the entry pathway of SARS-CoV-2 and the design of antivirals that target the membrane fusion step. url: https://doi.org/10.1101/2020.03.26.009233 doi: 10.1101/2020.03.26.009233 id: cord-327808-k3jec87p author: Zhu, Yunkai title: The S1/S2 boundary of SARS-CoV-2 spike protein modulates cell entry pathways and transmission date: 2020-08-25 words: 2754.0 sentences: 155.0 pages: flesch: 61.0 cache: ./cache/cord-327808-k3jec87p.txt txt: ./txt/cord-327808-k3jec87p.txt summary: We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. The sequence at the S1/S2 boundary contains a cleavage site for the furin protease, 61 which could preactivate the S protein for membrane fusion and potentially reduce the 62 dependence of SARS-CoV-2 on plasma membrane proteases, such as transmembrane 63 serine protease 2 (TMPRSS2), to enable efficient cell entry (Shang et al., 2020) . Intriguingly, 188 these genes edited also significantly inhibited the infection by pseudovirus bearing the 189 spike protein of MERS-CoV in A549-ACE2-DPP4 cells ( Figure 3D ). Although no infectious virus was detected by focus-forming 299 assay (data not shown), viral RNA levels were higher in fecal samples for Sfull (20 and 300 40-fold) than Sdel at days 2 and 4, respectively ( Figure 5B ). abstract: The global spread of SARS-CoV-2 is posing major public health challenges. One unique feature of SARS-CoV-2 spike protein is the insertion of multi-basic residues at the S1/S2 subunit cleavage site, the function of which remains uncertain. We found that the virus with intact spike (Sfull) preferentially enters cells via fusion at the plasma membrane, whereas a clone (Sdel) with deletion disrupting the multi-basic S1/S2 site instead utilizes a less efficient endosomal entry pathway. This idea was supported by the identification of a suite of endosomal entry factors specific to Sdel virus by a genome-wide CRISPR-Cas9 screen. A panel of host factors regulating the surface expression of ACE2 was identified for both viruses. Using a hamster model, animal-to-animal transmission with the Sdel virus was almost completely abrogated, unlike with Sfull. These findings highlight the critical role of the S1/S2 boundary of the SARS-CoV-2 spike protein in modulating virus entry and transmission. url: https://doi.org/10.1101/2020.08.25.266775 doi: 10.1101/2020.08.25.266775 id: cord-318478-fn0gcxbb author: Ziv, Omer title: The short- and long-range RNA-RNA Interactome of SARS-CoV-2 date: 2020-10-07 words: 5760.0 sentences: 343.0 pages: flesch: 56.0 cache: ./cache/cord-318478-fn0gcxbb.txt txt: ./txt/cord-318478-fn0gcxbb.txt summary: Available models for the RNA structure of SARS-CoV-2 and related viruses are largely confined to short-distance base-pairing which result in local folding of important cis-acting elements (Andrews et al., 2020; Huston et al., 2020; Kelly et al., 2020; Lan et al., 2020; Manfredonia et al., 2020; Ryder, 2020; Sanders et al., 2020; Sun et al., 2020) . In addition to the canonical UTR structures, we provide here a direct in vivo evidence for genome cyclization in SARS-CoV-2, mediated by long-range base-pairing between the 5′ and 3′ UTRs ( Figures 5B and S4B ). The long-distance RNA structure map for SARS-CoV-2 provides a practical starting point to dissect the regulation of discontinuous transcription, as it identifies cis-acting elements that interact with each other to create genome topologies that favour the synthesis of the ensemble of sgmRNAs. RNA viruses evolve sophisticated mechanisms to enhance the functional capacity of their size-restricted genomes and to regulate the expression levels of their replicase components. abstract: The Coronaviridae is a family of positive-strand RNA viruses that includes SARS-CoV-2, the etiologic agent of the COVID-19 pandemic. Bearing the largest single-stranded RNA genomes in nature, coronaviruses are critically dependent on long-distance RNA-RNA interactions to regulate the viral transcription and replication pathways. Here we experimentally mapped the in vivo RNA-RNA interactome of the full-length SARS-CoV-2 genome and subgenomic mRNAs. We uncovered a network of RNA-RNA interactions spanning tens of thousands of nucleotides. These interactions reveal that the viral genome and subgenomes adopt alternative topologies inside cells, and engage in different interactions with host RNAs. Notably, we discovered a long-range RNA-RNA interaction - the FSE-arch - that encircles the programmed ribosomal frameshifting element. The FSE-arch is conserved in the related MERS-CoV and is under purifying selection. Our findings illuminate RNA structure based mechanisms governing replication, discontinuous transcription, and translation of coronaviruses, and will aid future efforts to develop antiviral strategies. url: https://doi.org/10.1101/2020.07.19.211110 doi: 10.1101/2020.07.19.211110 id: cord-271978-j5enftje author: Zoltán, Köntös title: In Vitro Efficacy of “Essential Iodine Drops” Against Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) date: 2020-11-10 words: 2910.0 sentences: 153.0 pages: flesch: 52.0 cache: ./cache/cord-271978-j5enftje.txt txt: ./txt/cord-271978-j5enftje.txt summary: Conclusion Substantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARS-CoV-2 in vitro, demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasally to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients. Enthused by promising findings from a recent study by Pelletier and colleagues (12) , the present study was interested in Essential Iodine Drops (EID) for oral/nasal decontaminant in known or suspected cases of COVID-19 as a potentially better alternative to PVP-I. Briefly, the three dilutions of Essential Iodine Drops (EID) containing SARS-CoV-2 virus solution (1:1; 2:1 and 3:1) were tested in triplicates for virucidal activity as described by Pelletier and colleagues (12) . In vitro virucidal assay in the present study has indeed demonstrated that 75% and 50% of Essential Iodine Drops (EID) solution reduced SARS-CoV-2 virus titre after 60 seconds and 90 seconds of incubation by an LRV of 2.0 (99%). abstract: Background Aerosolization of respiratory droplets is considered the main route of coronavirus disease 2019 (COVID-19). Therefore, reducing the viral load of Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) shed via respiratory droplets is potentially an ideal strategy to prevent the spread of the pandemic. The in vitro virucidal activity of intranasal Povidone-Iodine (PVP-I) has been demonstrated recently to reduce SARS-CoV-2 viral titres. This study evaluated the virucidal activity of the aqueous solution of Iodine-V (a clathrate complex formed by elemental iodine and fulvic acid) as in Essential Iodine Drops (EID) with 200 μg elemental iodine/ml content against SARS-CoV-2 to ascertain whether it is a better alternative to PVP-I. Methods SARS-CoV-2 (USAWA1/2020 strain) virus stock was prepared by infecting Vero 76 cells (ATCC CRL-1587) until cytopathic effect (CPE). The virucidal activity of EID against SARS-CoV-2 was tested in three dilutions (1:1; 2:1 and 3:1) in triplicates by incubating at room temperature (22 ± 2°C) for either 60 or 90 seconds. The surviving viruses from each sample were quantified by a standard end-point dilution assay. Results EID (200 μg iodine/ml) after exposure for 60 and 90 seconds was compared to controls. In both cases, the viral titre was reduced by 99% (LRV 2.0). The 1:1 dilution of EID with virus reduced SARS-CoV-2 virus from 31,623 cell culture infectious dose 50% (CCCID50) to 316 CCID50 within 90 seconds. Conclusion Substantial reductions in LRV by Iodine-V in EID confirmed the activity of EID against SARS-CoV-2 in vitro, demonstrating that Iodine-V in EID is effective at inactivating the virus in vitro and therefore suggesting its potential application intranasally to reduce SARS-CoV-2 transmission from known or suspected COVID-19 patients. url: https://doi.org/10.1101/2020.11.07.370726 doi: 10.1101/2020.11.07.370726 id: cord-329129-t84pu00z author: Zuo, J title: Robust SARS-CoV-2-specific T-cell immunity is maintained at 6 months following primary infection date: 2020-11-02 words: 3486.0 sentences: 175.0 pages: flesch: 50.0 cache: ./cache/cord-329129-t84pu00z.txt txt: ./txt/cord-329129-t84pu00z.txt summary: We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection. In this study we characterised SARS-CoV-2-specific T cell immune responses in a cohort of 100 donors at 6-months post-infection. Peptide pools from a range of viral proteins, including spike, nucleoprotein and membrane protein, were used to stimulate fresh PBMC and the magnitude of the global SARS-CoV-2-specific T-cell response was determined. Here we undertook, to our knowledge, the first assessment of the SARS-CoV-2-specific T cell immune response at six months following primary infection in a unique cohort of healthy adults with asymptomatic or mild-to-moderate COVID-19. abstract: The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT and/or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary infection. url: https://doi.org/10.1101/2020.11.01.362319 doi: 10.1101/2020.11.01.362319 id: cord-321049-9ozn6il7 author: de Almeida, Paula Rodrigues title: SARS-CoV2 quantification using RT-dPCR: a faster and safer alternative to assist viral genomic copies assessment using RT-qPCR date: 2020-05-01 words: 1308.0 sentences: 73.0 pages: flesch: 49.0 cache: ./cache/cord-321049-9ozn6il7.txt txt: ./txt/cord-321049-9ozn6il7.txt summary: title: SARS-CoV2 quantification using RT-dPCR: a faster and safer alternative to assist viral genomic copies assessment using RT-qPCR Narrower confidence intervals, indicating high quantification precision were obtained in 100 and 1000-fold serial dilution and RT-dPCR results were equivalent between different assays in the same dilution. Here, we present a fast, accurate and simple method of viral titration using QuantStudio 3D® microchip based RT-dPCR to titrate SARS-CoV2 genomic copies from controls to be used in RT-qPCR assays for diagnosis and research purposes. A dilution that results in approximately 200 to 2000 target copies in the final reaction usually presents better precision values. Results with precision values below 5% were selected to estimate quantity of SARS-CoV2 genomic copies based on RT-dPCR. RT-dPCR results of 10-fold serial dilution of SARS-CoV2 control using assays for three targets in the Nucleocapsid gene. These results indicate that these primer-probe assays are suitable for SARS-CoV2 quantification through RT-dPCR. abstract: In this study, serial dilutions of SARS-CoV 2 RNA extract were tested using RT-dPCR using three different primer-probe assays aiming SARS-CoV 2 nucleocapsid coding region. Narrower confidence intervals, indicating high quantification precision were obtained in 100 and 1000-fold serial dilution and RT-dPCR results were equivalent between different assays in the same dilution. High accuracy of this test allowed conclusions regarding the ability of this technique to evaluate precisely the amount of genomic copies present in a sample. We believe that this fast and safe method can assist other researchers in titration of SARS-CoV2 controls used in RT-qPCR without the need of virus isolation. url: https://doi.org/10.1101/2020.05.01.072728 doi: 10.1101/2020.05.01.072728 id: cord-267223-pf799wbw author: de Lamballerie, Claire Nicolas title: Transcriptional profiling of immune and inflammatory responses in the context of SARS-CoV-2 fungal superinfection in a human airway epithelial model date: 2020-05-19 words: 1182.0 sentences: 75.0 pages: flesch: 31.0 cache: ./cache/cord-267223-pf799wbw.txt txt: ./txt/cord-267223-pf799wbw.txt summary: An increasing number of evidence indicate a relatively high prevalence of superinfections associated with COVID-19, including invasive aspergillosis, but the underlying mechanisms remain to be characterized. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyteand neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis in this specific context. Our results also highlight unique transcriptional 30 footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, 31 and an induction of several monocyte-and neutrophil associated chemokines, that could be 32 useful for the understanding of Aspergillus-associated COVID-19 and but also management 33 of severe forms of aspergillosis in this specific context. abstract: Superinfections of bacterial/fungal origin are known to affect the course and severity of respiratory viral infections. An increasing number of evidence indicate a relatively high prevalence of superinfections associated with COVID-19, including invasive aspergillosis, but the underlying mechanisms remain to be characterized. In the present study, to better understand the biological impact of superinfection we sought to determine and compare the host transcriptional response to SARS-CoV-2 versus Aspergillus superinfection, using a model of reconstituted humain airway epithelium. Our analyses reveal that both simple infection and superinfection induce a strong deregulation of core components of innate immune and inflammatory responses, with a stronger response to superinfection in the bronchial epithelial model compared to its nasal counterpart. Our results also highlight unique transcriptional footprints of SARS-CoV-2 Aspergillus superinfection, such as an imbalanced type I/type III IFN, and an induction of several monocyte- and neutrophil associated chemokines, that could be useful for the understanding of Aspergillus-associated COVID-19 and but also management of severe forms of aspergillosis in this specific context. url: https://doi.org/10.1101/2020.05.19.103630 doi: 10.1101/2020.05.19.103630 id: cord-104146-pabh3ajb author: de Lussanet de la Sablonière, Marc H. E. title: Robust, general purpose, digital power line hum filter which is free of deformations and which can be applied to large transients date: 2019-11-04 words: 3463.0 sentences: 199.0 pages: flesch: 66.0 cache: ./cache/cord-104146-pabh3ajb.txt txt: ./txt/cord-104146-pabh3ajb.txt summary: The resulting periodic median subtraction (PMS) filter reliably removes hum of any harmonic composition, even if the ground frequency is lacking. Even though power 25 line noise is mostly highly regular in frequency, amplitude and wave form, it has proven notoriously difficult to design a filter that is free of artifacts and deformations, which leaves the original signal intact. Subtraction-type filters aim to fit the shape and amplitude of the hum 50 noise directly from the data, sometimes from multiple channels (e.g., in EEG signals) or from a reference channel (e.g. Wan et al., 2006; Lin et al., 2016) . Increasing the filter window of the PMS filter from 50 to 500 periods (10 s) reduced the median absolute error in white noise data to 0.037, which is equivalent to the error in a signal with an HF amplitude of 0.2 (cf. abstract: Power line interference (“hum noise”) is a common source of noise in recorded biological data. It has a highly constant frequency with harmonics and little variation in amplitude and wave shape. In contrast to stochastic noise it is phasic, i.e., the phase relation remains constant across long intervals. In digital recordings, the measurement frequency is typically very close to a multiple of the hum frequency (50 or 60 Hz). Common filters introduce various kinds of distortions and errors. The here proposed subtraction method makes use of the specific properties of power line hum. For this, it computes a moving estimate of the hum noise by taking the periodic median of the high-pass filtered signal. The resulting periodic median subtraction (PMS) filter reliably removes hum of any harmonic composition, even if the ground frequency is lacking. The filter is completely free of border artifacts. It does not introduce distortions, even if around sharp transients such as in force plate recordings of jumping. The filter is validated on recorded and artificial data. The errors are quantified. The results also show that the errors of hum filters generally increase with the high-frequency content of the data. Thus, the removal of hum from a force plate recording generally gives better results than from an EMG recoding. Compared to other filters, the errors of the PMS filter are generally lower than the best hum filters currently known. url: https://doi.org/10.1101/830463 doi: 10.1101/830463 id: cord-331888-lbtuvdv3 author: de Souza, Dalton Garcia Borges title: Forecasting COVID-19 cases at the Amazon region: a comparison of classical and machine learning models date: 2020-10-09 words: 2434.0 sentences: 178.0 pages: flesch: 61.0 cache: ./cache/cord-331888-lbtuvdv3.txt txt: ./txt/cord-331888-lbtuvdv3.txt summary: title: Forecasting COVID-19 cases at the Amazon region: a comparison of classical and machine learning models We compare the models autoregressive integrated moving average (ARIMA), Holt-Winters, support vector regression (SVR), k-nearest neighbors regressor (KNN), random trees regressor (RTR), seasonal linear regression with change-points (Prophet), and simple logistic regression (SLR). We evaluate the models according to their capacity to forecast in different historical scenarios of the COVID-19 progression, such as exponential increases, sudden decreases, and stability periods of daily cases. Holt-Winters, support vector regression (SVR), k-nearest neighbors regressor (KNN), 43 random trees regressor (RT), seasonal linear regression with change-points (SLiR) and 44 simple logistic regression (SLR), which dictates the baseline performance in this study. Thus, in this paper, we compared classical and machine learning models to forecast 231 the evolution of COVID-19 in the state. Application of ARIMA and Holt-Winters forecasting model to predict 294 the spreading of COVID-19 for India and its states abstract: BACKGROUND Since the first reports of COVID-19, decision-makers have been using traditional epidemiological models to predict the days to come. However, the enhancement of computational power, the demand for adaptable predictive frameworks, the short past of the disease, and uncertainties related to input data and prediction rules, also make other classical and machine learning techniques viable options. OBJECTIVE This study investigates the efficiency of six models in forecasting COVID-19 confirmed cases with 17 days ahead. We compare the models autoregressive integrated moving average (ARIMA), Holt-Winters, support vector regression (SVR), k-nearest neighbors regressor (KNN), random trees regressor (RTR), seasonal linear regression with change-points (Prophet), and simple logistic regression (SLR). MATERIAL AND METHODS We implement the models to data provided by the health surveillance secretary of Amapáa, a Brazilian state fully carved in the Amazon rainforest, which has been experiencing high infection rates. We evaluate the models according to their capacity to forecast in different historical scenarios of the COVID-19 progression, such as exponential increases, sudden decreases, and stability periods of daily cases. To do so, we use a rolling forward splitting approach for out-of-sample validation. We employ the metrics RMSE, R-squared, and sMAPE in evaluating the model in different cross-validation sections. FINDINGS All models outperform SLG, especially Holt-Winters, that performs satisfactorily in all scenarios. SVR and ARIMA have better performances in isolated scenarios. To implement the comparisons, we have created a web application, which is available online. CONCLUSION This work represents an effort to assist the decision-makers of Amapá in future decisions to come, especially under scenarios of sudden variations in the number of confirmed cases of Amapá, which would be caused, for instance, by new contamination waves or vaccination. It is also an attempt to highlight alternative models that could be used in future epidemics. url: https://doi.org/10.1101/2020.10.09.332908 doi: 10.1101/2020.10.09.332908 id: cord-103435-yufvt44t author: van Aalst, Marvin title: Constructing and analysing dynamic models with modelbase v1.0 - a software update date: 2020-10-02 words: 4085.0 sentences: 208.0 pages: flesch: 37.0 cache: ./cache/cord-103435-yufvt44t.txt txt: ./txt/cord-103435-yufvt44t.txt summary: Background Computational mathematical models of biological and biomedical systems have been successfully applied to advance our understanding of various regulatory processes, metabolic fluxes, effects of drug therapies and disease evolution or transmission. Results and Discussion We provide here the update on the development of modelbase, a free expandable Python package for constructing and analysing ordinary differential equation-based mathematical models of dynamic systems. Most recently, deterministic models simulating the dynamics of infectious diseases gained the interest of the general public during our combat of the Covid-19 pandemic, when a large number of ODE based mathematical models has been developed and discussed even in nonscientific journals (see for example [3] [4] [5] ). Implementation modelbase is a Python package to facilitate construction and analysis of ODE based mathematical models of biological systems. We are presenting here updates of our modelling software that has been developed to simplify the building process of mathematical models based on ODEs. modelbase is fully embedded in the Python programming language. abstract: Background Computational mathematical models of biological and biomedical systems have been successfully applied to advance our understanding of various regulatory processes, metabolic fluxes, effects of drug therapies and disease evolution or transmission. Unfortunately, despite community efforts leading to the development of SBML or the BioModels database, many published models have not been fully exploited, largely due to lack of proper documentation or the dependence on proprietary software. To facilitate synergies within the emerging research fields of systems biology and medicine by reusing and further developing existing models, an open-source toolbox that makes the overall process of model construction more consistent, understandable, transparent and reproducible is desired. Results and Discussion We provide here the update on the development of modelbase, a free expandable Python package for constructing and analysing ordinary differential equation-based mathematical models of dynamic systems. It provides intuitive and unified methods to construct and solve these systems. Significantly expanded visualisation methods allow convenient analyses of structural and dynamic properties of the models. Specifying reaction stoichiometries and rate equations, the system of differential equations is assembled automatically. A newly provided library of common kinetic rate laws highly reduces the repetitiveness of the computer programming code, and provides full SBML compatibility. Previous versions provided functions for automatic construction of networks for isotope labelling studies. Using user-provided label maps, modelbase v1.0 streamlines the expansion of classic models to their isotope-specific versions. Finally, the library of previously published models implemented in modelbase is continuously growing. Ranging from photosynthesis over tumour cell growth to viral infection evolution, all models are available now in a transparent, reusable and unified format using modelbase. Conclusion With the small price of learning a new software package, which is written in Python, currently one of the most popular programming languages, the user can develop new models and actively profit from the work of others, repeating and reproducing models in a consistent, tractable and expandable manner. Moreover, the expansion of models to their label specific versions enables simulating label propagation, thus providing quantitative information regarding network topology and metabolic fluxes. url: https://doi.org/10.1101/2020.09.30.321380 doi: 10.1101/2020.09.30.321380 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel