Carrel name: keyword-ebov-cord Creating study carrel named keyword-ebov-cord Initializing database file: cache/cord-002013-rb9xdzro.json key: cord-002013-rb9xdzro authors: Zheng, Xuexing; Wong, Gary; Zhao, Yongkun; Wang, Hualei; He, Shihua; Bi, Yuhai; Chen, Weijin; Jin, Hongli; Gai, Weiwei; Chu, Di; Cao, Zengguo; Wang, Chong; Fan, Quanshui; Chi, Hang; Gao, Yuwei; Wang, Tiecheng; Feng, Na; Yan, Feihu; Huang, Geng; Zheng, Ying; Li, Nan; Li, Yuetao; Qian, Jun; Zou, Yong; Kobinger, Gary; Gao, George Fu; Qiu, Xiangguo; Yang, Songtao; Xia, Xianzhu title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date: 2016-04-12 journal: Sci Rep DOI: 10.1038/srep24179 sha: doc_id: 2013 cord_uid: rb9xdzro file: cache/cord-002676-zwkl1ywk.json key: cord-002676-zwkl1ywk authors: Yu, Dong-Shan; Weng, Tian-Hao; Wu, Xiao-Xin; Wang, Frederick X.C.; Lu, Xiang-Yun; Wu, Hai-Bo; Wu, Nan-Ping; Li, Lan-Juan; Yao, Hang-Ping title: The lifecycle of the Ebola virus in host cells date: 2017-06-15 journal: Oncotarget DOI: 10.18632/oncotarget.18498 sha: doc_id: 2676 cord_uid: zwkl1ywk file: cache/cord-001764-njzyu4mv.json key: cord-001764-njzyu4mv authors: Hofmann-Winkler, Heike; Gnirß, Kerstin; Wrensch, Florian; Pöhlmann, Stefan title: Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976 date: 2015-10-01 journal: J Infect Dis DOI: 10.1093/infdis/jiv101 sha: doc_id: 1764 cord_uid: njzyu4mv 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-001546-ndz3oarf.json key: cord-001546-ndz3oarf authors: Ayithan, Natarajan; Bradfute, Steven B.; Anthony, Scott M.; Stuthman, Kelly S.; Bavari, Sina; Bray, Mike; Ozato, Keiko title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 journal: PLoS One DOI: 10.1371/journal.pone.0118345 sha: doc_id: 1546 cord_uid: ndz3oarf file: cache/cord-274377-57zy6unz.json key: cord-274377-57zy6unz authors: Long, Jason; Wright, Edward; Molesti, Eleonora; Temperton, Nigel; Barclay, Wendy title: Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry date: 2015-02-10 journal: F1000Res DOI: 10.12688/f1000research.6085.2 sha: doc_id: 274377 cord_uid: 57zy6unz file: cache/cord-296517-414grqif.json key: cord-296517-414grqif authors: Wong, Gary; Liu, Wenjun; Liu, Yingxia; Zhou, Boping; Bi, Yuhai; Gao, George F. title: MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease date: 2015-10-14 journal: Cell Host & Microbe DOI: 10.1016/j.chom.2015.09.013 sha: doc_id: 296517 cord_uid: 414grqif file: cache/cord-011129-btaxvmsr.json key: cord-011129-btaxvmsr authors: Di Paola, Nicholas; Sanchez-Lockhart, Mariano; Zeng, Xiankun; Kuhn, Jens H.; Palacios, Gustavo title: Viral genomics in Ebola virus research date: 2020-05-04 journal: Nat Rev Microbiol DOI: 10.1038/s41579-020-0354-7 sha: doc_id: 11129 cord_uid: btaxvmsr file: cache/cord-284845-on97zu6w.json key: cord-284845-on97zu6w authors: Falcinelli, Shane D.; Chertow, Daniel S.; Kindrachuk, Jason title: Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections date: 2016-07-29 journal: ACS Infectious Diseases DOI: 10.1021/acsinfecdis.6b00104 sha: doc_id: 284845 cord_uid: on97zu6w file: cache/cord-300133-yc2wxgid.json key: cord-300133-yc2wxgid authors: Martínez, Miguel J.; Salim, Abdulbaset M.; Hurtado, Juan C.; Kilgore, Paul E. title: Ebola Virus Infection: Overview and Update on Prevention and Treatment date: 2015-09-12 journal: Infect Dis Ther DOI: 10.1007/s40121-015-0079-5 sha: doc_id: 300133 cord_uid: yc2wxgid file: cache/cord-000547-adfigzc1.json key: cord-000547-adfigzc1 authors: Beniac, Daniel R.; Melito, Pasquale L.; deVarennes, Shauna L.; Hiebert, Shannon L.; Rabb, Melissa J.; Lamboo, Lindsey L.; Jones, Steven M.; Booth, Timothy F. title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date: 2012-01-11 journal: PLoS One DOI: 10.1371/journal.pone.0029608 sha: doc_id: 547 cord_uid: adfigzc1 file: cache/cord-001513-p7v5p036.json key: cord-001513-p7v5p036 authors: Ekins, Sean; Freundlich, Joel S.; Coffee, Megan title: A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus date: 2014-12-12 journal: F1000Res DOI: 10.12688/f1000research.5741.2 sha: doc_id: 1513 cord_uid: p7v5p036 file: cache/cord-004335-bw3tziup.json key: cord-004335-bw3tziup authors: Perez-Zsolt, Daniel; Martinez-Picado, Javier; Izquierdo-Useros, Nuria title: When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date: 2019-12-19 journal: Viruses DOI: 10.3390/v12010008 sha: doc_id: 4335 cord_uid: bw3tziup file: cache/cord-002935-jq1xumrh.json key: cord-002935-jq1xumrh authors: Postnikova, Elena; Cong, Yu; DeWald, Lisa Evans; Dyall, Julie; Yu, Shuiqing; Hart, Brit J.; Zhou, Huanying; Gross, Robin; Logue, James; Cai, Yingyun; Deiuliis, Nicole; Michelotti, Julia; Honko, Anna N.; Bennett, Richard S.; Holbrook, Michael R.; Olinger, Gene G.; Hensley, Lisa E.; Jahrling, Peter B. title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date: 2018-03-22 journal: PLoS One DOI: 10.1371/journal.pone.0194880 sha: doc_id: 2935 cord_uid: jq1xumrh file: cache/cord-000804-0hlj6r10.json key: cord-000804-0hlj6r10 authors: Brauburger, Kristina; Hume, Adam J.; Mühlberger, Elke; Olejnik, Judith title: Forty-Five Years of Marburg Virus Research date: 2012-10-01 journal: Viruses DOI: 10.3390/v4101878 sha: doc_id: 804 cord_uid: 0hlj6r10 file: cache/cord-288029-6l91knu3.json key: cord-288029-6l91knu3 authors: Elfiky, Abdo A. title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction date: 2020-04-14 journal: Cell Stress Chaperones DOI: 10.1007/s12192-020-01106-z sha: doc_id: 288029 cord_uid: 6l91knu3 file: cache/cord-002185-oz7hras7.json key: cord-002185-oz7hras7 authors: Nelson, Elizabeth A.; Barnes, Alyson B.; Wiehle, Ronald D.; Fontenot, Gregory K.; Hoenen, Thomas; White, Judith M. title: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date: 2016-08-02 journal: Viruses DOI: 10.3390/v8080206 sha: doc_id: 2185 cord_uid: oz7hras7 file: cache/cord-293481-bmfj50fb.json key: cord-293481-bmfj50fb authors: Malin, Jakob J.; Suárez, Isabelle; Priesner, Vanessa; Fätkenheuer, Gerd; Rybniker, Jan title: Remdesivir against COVID-19 and Other Viral Diseases date: 2020-10-14 journal: Clin Microbiol Rev DOI: 10.1128/cmr.00162-20 sha: doc_id: 293481 cord_uid: bmfj50fb file: cache/cord-002500-9p2n8tjx.json key: cord-002500-9p2n8tjx authors: Lambe, Teresa; Bowyer, Georgina; Ewer, Katie J title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? date: 2017-05-26 journal: Philos Trans R Soc Lond B Biol Sci DOI: 10.1098/rstb.2016.0295 sha: doc_id: 2500 cord_uid: 9p2n8tjx file: cache/cord-344316-mwnnmwnw.json key: cord-344316-mwnnmwnw authors: Herst, C.V.; Burkholz, S.; Sidney, J.; Sette, A.; Harris, P.E.; Massey, S.; Brasel, T.; Cunha-Neto, E.; Rosa, D.S.; Chao, W.C.H.; Carback, R.; Hodge, T.; Wang, L.; Ciotlos, S.; Lloyd, P.; Rubsamen, R. title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design date: 2020-04-28 journal: Vaccine DOI: 10.1016/j.vaccine.2020.04.034 sha: doc_id: 344316 cord_uid: mwnnmwnw file: cache/cord-279152-yh7x7w2q.json key: cord-279152-yh7x7w2q authors: Ndungo, Esther; Herbert, Andrew S.; Raaben, Matthijs; Obernosterer, Gregor; Biswas, Rohan; Miller, Emily Happy; Wirchnianski, Ariel S.; Carette, Jan E.; Brummelkamp, Thijn R.; Whelan, Sean P.; Dye, John M.; Chandran, Kartik title: A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles date: 2016-03-30 journal: mSphere DOI: 10.1128/msphere.00007-16 sha: doc_id: 279152 cord_uid: yh7x7w2q file: cache/cord-276437-5gkdotvt.json key: cord-276437-5gkdotvt authors: Liu, William J.; Shi, Weifeng; Zhu, Wuyang; Jin, Cong; Zou, Shumei; Wang, Ji; Ke, Yuehua; Li, Xiaofeng; Liu, Mi; Hu, Tao; Fan, Hang; Tong, Yigang; Zhao, Xiang; Chen, Wenbin; Zhao, Yuhui; Liu, Di; Wong, Gary; Chen, Chengchao; Geng, Chunyu; Xie, Weiwei; Jiang, Hui; Kamara, Idrissa Laybor; Kamara, Abdul; Lebby, Matt; Kargbo, Brima; Qiu, Xiangguo; Wang, Yu; Liang, Xiaofeng; Liang, Mifang; Dong, Xiaoping; Wu, Guizhen; Gao, George F.; Shu, Yuelong title: Intra-host Ebola viral adaption during human infection date: 2019-02-20 journal: Biosaf Health DOI: 10.1016/j.bsheal.2019.02.001 sha: doc_id: 276437 cord_uid: 5gkdotvt file: cache/cord-289413-mbrw85og.json key: cord-289413-mbrw85og authors: Flego, Michela; Frau, Aldo; Accardi, Luisa; Mallano, Alessandra; Ascione, Alessandro; Gellini, Mara; Fanunza, Elisa; Vella, Stefano; Di Bonito, Paola; Tramontano, Enzo title: Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity date: 2019-09-05 journal: BMC Biotechnol DOI: 10.1186/s12896-019-0554-2 sha: doc_id: 289413 cord_uid: mbrw85og file: cache/cord-004126-u6ts87ur.json key: cord-004126-u6ts87ur authors: Furuyama, Wakako; Reynolds, Pierce; Haddock, Elaine; Meade-White, Kimberly; Quynh Le, Mai; Kawaoka, Yoshihiro; Feldmann, Heinz; Marzi, Andrea title: A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades date: 2020-01-10 journal: NPJ Vaccines DOI: 10.1038/s41541-019-0155-z sha: doc_id: 4126 cord_uid: u6ts87ur file: cache/cord-004069-nuep8nim.json key: cord-004069-nuep8nim authors: DeWald, Lisa Evans; Johnson, Joshua C.; Gerhardt, Dawn M.; Torzewski, Lisa M.; Postnikova, Elena; Honko, Anna N.; Janosko, Krisztina; Huzella, Louis; Dowling, William E.; Eakin, Ann E.; Osborn, Blaire L.; Gahagen, Janet; Tang, Liang; Green, Carol E.; Mirsalis, Jon C.; Holbrook, Michael R.; Jahrling, Peter B.; Dyall, Julie; Hensley, Lisa E. title: In Vivo Activity of Amodiaquine against Ebola Virus Infection date: 2019-12-27 journal: Sci Rep DOI: 10.1038/s41598-019-56481-0 sha: doc_id: 4069 cord_uid: nuep8nim file: cache/cord-318587-ewvnkdr2.json key: cord-318587-ewvnkdr2 authors: Steeds, Kimberley; Hall, Yper; Slack, Gillian S.; Longet, Stephanie; Strecker, Thomas; Fehling, Sarah Katharina; Wright, Edward; Bore, Joseph Akoi; Koundouno, Fara Raymond; Konde, Mandy Kader; Hewson, Roger; Hiscox, Julian A.; Pollakis, Georgios; Carroll, Miles W. title: Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date: 2020-08-31 journal: Sci Rep DOI: 10.1038/s41598-020-71225-1 sha: doc_id: 318587 cord_uid: ewvnkdr2 file: cache/cord-003779-5yhoiv76.json key: cord-003779-5yhoiv76 authors: Singleton, Courtney D.; Humby, Monica S.; Yi, Hyun Ah; Rizzo, Robert C.; Jacobs, Amy title: Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry date: 2019-07-17 journal: J Virol DOI: 10.1128/jvi.00676-19 sha: doc_id: 3779 cord_uid: 5yhoiv76 file: cache/cord-017811-w38mbvdw.json key: cord-017811-w38mbvdw authors: Volchkov, Viktor; Klenk, Hans Dieter title: Proteolytic Processing of Filovirus Glycoproteins date: 2018-02-16 journal: Activation of Viruses by Host Proteases DOI: 10.1007/978-3-319-75474-1_5 sha: doc_id: 17811 cord_uid: w38mbvdw file: cache/cord-267941-nrluar4e.json key: cord-267941-nrluar4e authors: Park, Eun-Mee; Park, Sun-Whan; Lee, Ye-Ji; Lee, Won-Ja; Choi, Wooyoung title: Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells date: 2018-08-23 journal: J Virol Methods DOI: 10.1016/j.jviromet.2018.08.016 sha: doc_id: 267941 cord_uid: nrluar4e file: cache/cord-102206-mb0qcd0b.json key: cord-102206-mb0qcd0b authors: Seymour, Elif; Ünlü, Nese Lortlar; Carter, Eric P.; Connor, John H.; Ünlü, M. 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Mu, Yi; Houston, Hollis; Martinez-Smith, Marla; Noble-Wang, Judith; Coulliette-Salmond, Angela; Rose, Laura title: Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate date: 2020-08-18 journal: Appl Environ Microbiol DOI: 10.1128/aem.01482-20 sha: doc_id: 284791 cord_uid: bgodmbru file: cache/cord-303647-c4umbcvn.json key: cord-303647-c4umbcvn authors: Reed, Patricia E.; Mulangu, Sabue; Cameron, Kenneth N.; Ondzie, Alain U.; Joly, Damien; Bermejo, Magdalena; Rouquet, Pierre; Fabozzi, Giulia; Bailey, Michael; Shen, Zhimin; Keele, Brandon F.; Hahn, Beatrice; Karesh, William B.; Sullivan, Nancy J. title: A New Approach for Monitoring Ebolavirus in Wild Great Apes date: 2014-09-18 journal: PLoS Negl Trop Dis DOI: 10.1371/journal.pntd.0003143 sha: doc_id: 303647 cord_uid: c4umbcvn file: cache/cord-288734-xinkqs6u.json key: cord-288734-xinkqs6u authors: Muñoz-Fontela, César; McElroy, Anita K. title: Ebola Virus Disease in Humans: Pathophysiology and Immunity date: 2017-03-30 journal: Marburg- and Ebolaviruses DOI: 10.1007/82_2017_11 sha: doc_id: 288734 cord_uid: xinkqs6u file: cache/cord-003917-bswndfvk.json key: cord-003917-bswndfvk authors: Lalle, Eleonora; Biava, Mirella; Nicastri, Emanuele; Colavita, Francesca; Di Caro, Antonino; Vairo, Francesco; Lanini, Simone; Castilletti, Concetta; Langer, Martin; Zumla, Alimuddin; Kobinger, Gary; Capobianchi, Maria R.; Ippolito, Giuseppe title: Pulmonary Involvement during the Ebola Virus Disease date: 2019-08-24 journal: Viruses DOI: 10.3390/v11090780 sha: doc_id: 3917 cord_uid: bswndfvk file: cache/cord-355737-o0y4rn0z.json key: cord-355737-o0y4rn0z authors: Ng, Melinda; Ndungo, Esther; Kaczmarek, Maria E; Herbert, Andrew S; Binger, Tabea; Kuehne, Ana I; Jangra, Rohit K; Hawkins, John A; Gifford, Robert J; Biswas, Rohan; Demogines, Ann; James, Rebekah M; Yu, Meng; Brummelkamp, Thijn R; Drosten, Christian; Wang, Lin-Fa; Kuhn, Jens H; Müller, Marcel A; Dye, John M; Sawyer, Sara L; Chandran, Kartik title: Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats date: 2015-12-23 journal: eLife DOI: 10.7554/elife.11785 sha: doc_id: 355737 cord_uid: o0y4rn0z file: cache/cord-327641-hqnem2zs.json key: cord-327641-hqnem2zs authors: Ji, Ying-Jie; Duan, Xue-Zhang; Gao, Xu-Dong; Li, Lei; Li, Chen; Ji, Dong; Li, Wen-Gang; Wang, Li-Fu; Meng, Yu-Hua; Yang, Xiao; Ling, Bin-Fang; Song, Xue-Ai; Gu, Mei-Lei; Jiang, Tao; Koroma, She-Ku M.; Bangalie, James; Duan, Hui-Juan title: Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone date: 2016-11-03 journal: Infect Dis Poverty DOI: 10.1186/s40249-016-0195-9 sha: doc_id: 327641 cord_uid: hqnem2zs file: cache/cord-001542-f089bs8r.json key: cord-001542-f089bs8r authors: Lai, Kang Yiu; Ng, Wing Yiu George; Cheng, Fan Fanny title: Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date: 2014-11-28 journal: Infect Dis Poverty DOI: 10.1186/2049-9957-3-43 sha: doc_id: 1542 cord_uid: f089bs8r file: cache/cord-330647-w1bpeqzg.json key: cord-330647-w1bpeqzg authors: Wong, Samson Sai-Yin; Wong, Sally Cheuk-Ying title: Ebola virus disease in nonendemic countries date: 2015-05-31 journal: Journal of the Formosan Medical Association DOI: 10.1016/j.jfma.2015.01.012 sha: doc_id: 330647 cord_uid: w1bpeqzg file: cache/cord-272576-ez731lif.json key: cord-272576-ez731lif authors: Wada, Yoshiko; Wada, Kennosuke; Iwasaki, Yuki; Kanaya, Shigehiko; Ikemura, Toshimichi title: Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date: 2016-11-03 journal: Sci Rep DOI: 10.1038/srep36197 sha: doc_id: 272576 cord_uid: ez731lif file: cache/cord-354068-4qlk6y7h.json key: cord-354068-4qlk6y7h authors: Friedrich, Brian M.; Trefry, John C.; Biggins, Julia E.; Hensley, Lisa E.; Honko, Anna N.; Smith, Darci R.; Olinger, Gene G. title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date: 2012-09-21 journal: Viruses DOI: 10.3390/v4091619 sha: doc_id: 354068 cord_uid: 4qlk6y7h file: cache/cord-297082-2rhoffx2.json key: cord-297082-2rhoffx2 authors: Yu, Changqing; Li, Sunan; Zhang, Xianfeng; Khan, Ilyas; Ahmad, Iqbal; Zhou, Yulong; Li, Shuo; Shi, Jing; Wang, Yu; Zheng, Yong-Hui title: MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date: 2020-09-15 journal: mBio DOI: 10.1128/mbio.01882-20 sha: doc_id: 297082 cord_uid: 2rhoffx2 file: cache/cord-336986-rmxin1da.json key: cord-336986-rmxin1da authors: De Clercq, Erik title: New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections date: 2019-08-07 journal: Chem Asian J DOI: 10.1002/asia.201900841 sha: doc_id: 336986 cord_uid: rmxin1da file: cache/cord-002463-qhtj1pef.json key: cord-002463-qhtj1pef authors: Dash, Raju; Das, Rasel; Junaid, Md; Akash, Md Forhad Chowdhury; Islam, Ashekul; Hosen, SM Zahid title: In silico-based vaccine design against Ebola virus glycoprotein date: 2017-03-21 journal: Adv Appl Bioinform Chem DOI: 10.2147/aabc.s115859 sha: doc_id: 2463 cord_uid: qhtj1pef file: cache/cord-256187-ofp7tupv.json key: cord-256187-ofp7tupv authors: Kühl, A.; Pöhlmann, S. title: How Ebola Virus Counters the Interferon System date: 2012-09-07 journal: Zoonoses Public Health DOI: 10.1111/j.1863-2378.2012.01454.x sha: doc_id: 256187 cord_uid: ofp7tupv file: cache/cord-337998-08tknscm.json key: cord-337998-08tknscm authors: Sztuba-Solinska, Joanna; Diaz, Larissa; Kumar, Mia R.; Kolb, Gaëlle; Wiley, Michael R.; Jozwick, Lucas; Kuhn, Jens H.; Palacios, Gustavo; Radoshitzky, Sheli R.; J. Le Grice, Stuart F.; Johnson, Reed F. title: A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8 date: 2016-11-16 journal: Nucleic Acids Res DOI: 10.1093/nar/gkw825 sha: doc_id: 337998 cord_uid: 08tknscm file: cache/cord-322748-a5131tv9.json key: cord-322748-a5131tv9 authors: Yates, Mary K.; Raje, Mithun R.; Chatterjee, Payel; Spiropoulou, Christina F.; Bavari, Sina; Flint, Mike; Soloveva, Veronica; Seley-Radtke, Katherine L. title: Flex-nucleoside analogues – Novel therapeutics against filoviruses date: 2017-06-15 journal: Bioorganic & Medicinal Chemistry Letters DOI: 10.1016/j.bmcl.2017.04.069 sha: doc_id: 322748 cord_uid: a5131tv9 file: cache/cord-334560-1j9zmuub.json key: cord-334560-1j9zmuub authors: Hunt, Catherine L.; Lennemann, Nicholas J.; Maury, Wendy title: Filovirus Entry: A Novelty in the Viral Fusion World date: 2012-02-07 journal: Viruses DOI: 10.3390/v4020258 sha: doc_id: 334560 cord_uid: 1j9zmuub file: cache/cord-294342-7ycgd0h7.json key: cord-294342-7ycgd0h7 authors: Markosyan, Ruben M.; Miao, Chunhui; Zheng, Yi-Min; Melikyan, Gregory B.; Liu, Shan-Lu; Cohen, Fredric S. title: Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date: 2016-01-05 journal: PLoS Pathog DOI: 10.1371/journal.ppat.1005373 sha: doc_id: 294342 cord_uid: 7ycgd0h7 file: cache/cord-296399-vvbjulm9.json key: cord-296399-vvbjulm9 authors: Brinkmann, Constantin; Hoffmann, Markus; Lübke, Anastasia; Nehlmeier, Inga; Krämer-Kühl, Annika; Winkler, Michael; Pöhlmann, Stefan title: The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date: 2017-12-07 journal: PLoS One DOI: 10.1371/journal.pone.0189073 sha: doc_id: 296399 cord_uid: vvbjulm9 file: cache/cord-325423-d212h4bp.json key: cord-325423-d212h4bp authors: Carrion, Ricardo; Ro, Youngtae; Hoosien, Kareema; Ticer, Anysha; Brasky, Kathy; de la Garza, Melissa; Mansfield, Keith; Patterson, Jean L. title: A small nonhuman primate model for filovirus-induced disease date: 2011-11-01 journal: Virology DOI: 10.1016/j.virol.2011.08.022 sha: doc_id: 325423 cord_uid: d212h4bp file: cache/cord-342052-v4y1xc90.json key: cord-342052-v4y1xc90 authors: Horigan, Verity; Gale, Paul; Kosmider, Rowena D.; Minnis, Christopher; Snary, Emma L.; Breed, Andrew C.; Simons, Robin R.L. title: Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States date: 2017-10-02 journal: Microb Risk Anal DOI: 10.1016/j.mran.2017.09.002 sha: doc_id: 342052 cord_uid: v4y1xc90 file: cache/cord-350083-kldu8q8x.json key: cord-350083-kldu8q8x authors: Oany, Arafat Rahman; Sharmin, Tahmina; Chowdhury, Afrin Sultana; Jyoti, Tahmina Pervin; Hasan, Md. Anayet title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach date: 2015-08-08 journal: In Silico Pharmacol DOI: 10.1186/s40203-015-0011-4 sha: doc_id: 350083 cord_uid: kldu8q8x file: cache/cord-350565-mejd7blb.json key: cord-350565-mejd7blb authors: Lewnard, Joseph A; Reingold, Arthur L title: Emerging Challenges and Opportunities in Infectious Disease Epidemiology date: 2019-03-16 journal: Am J Epidemiol DOI: 10.1093/aje/kwy264 sha: doc_id: 350565 cord_uid: mejd7blb file: cache/cord-352492-6ihyiwgb.json key: cord-352492-6ihyiwgb authors: Eickmann, Markus; Gravemann, Ute; Handke, Wiebke; Tolksdorf, Frank; Reichenberg, Stefan; Müller, Thomas H.; Seltsam, Axel title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively date: 2018-05-06 journal: Transfusion DOI: 10.1111/trf.14652 sha: doc_id: 352492 cord_uid: 6ihyiwgb file: cache/cord-335093-tc1qo2k0.json key: cord-335093-tc1qo2k0 authors: Gehring, Gerrit; Rohrmann, Katrin; Atenchong, Nkacheh; Mittler, Eva; Becker, Stephan; Dahlmann, Franziska; Pöhlmann, Stefan; Vondran, Florian W. R.; David, Sascha; Manns, Michael P.; Ciesek, Sandra; von Hahn, Thomas title: The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry date: 2014-08-01 journal: J Antimicrob Chemother DOI: 10.1093/jac/dku091 sha: doc_id: 335093 cord_uid: tc1qo2k0 file: cache/cord-305653-f9vqn96o.json key: cord-305653-f9vqn96o authors: Schmidt, Rebecca; Beltzig, Lea C.; Sawatsky, Bevan; Dolnik, Olga; Dietzel, Erik; Krähling, Verena; Volz, Asisa; Sutter, Gerd; Becker, Stephan; von Messling, Veronika title: Generation of therapeutic antisera for emerging viral infections date: 2018-10-05 journal: NPJ Vaccines DOI: 10.1038/s41541-018-0082-4 sha: doc_id: 305653 cord_uid: f9vqn96o Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-ebov-cord === 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-267941-nrluar4e author: Park, Eun-Mee title: Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells date: 2018-08-23 pages: extension: .txt txt: ./txt/cord-267941-nrluar4e.txt cache: ./cache/cord-267941-nrluar4e.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-267941-nrluar4e.txt' === file2bib.sh === id: cord-322748-a5131tv9 author: Yates, Mary K. title: Flex-nucleoside analogues – Novel therapeutics against filoviruses date: 2017-06-15 pages: extension: .txt txt: ./txt/cord-322748-a5131tv9.txt cache: ./cache/cord-322748-a5131tv9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-322748-a5131tv9.txt' === file2bib.sh === id: cord-288029-6l91knu3 author: Elfiky, Abdo A. title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction date: 2020-04-14 pages: extension: .txt txt: ./txt/cord-288029-6l91knu3.txt cache: ./cache/cord-288029-6l91knu3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-288029-6l91knu3.txt' === file2bib.sh === id: cord-296517-414grqif author: Wong, Gary title: MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease date: 2015-10-14 pages: extension: .txt txt: ./txt/cord-296517-414grqif.txt cache: ./cache/cord-296517-414grqif.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-296517-414grqif.txt' === file2bib.sh === id: cord-336986-rmxin1da author: De Clercq, Erik title: New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections date: 2019-08-07 pages: extension: .txt txt: ./txt/cord-336986-rmxin1da.txt cache: ./cache/cord-336986-rmxin1da.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-336986-rmxin1da.txt' === file2bib.sh === id: cord-017811-w38mbvdw author: Volchkov, Viktor title: Proteolytic Processing of Filovirus Glycoproteins date: 2018-02-16 pages: extension: .txt txt: ./txt/cord-017811-w38mbvdw.txt cache: ./cache/cord-017811-w38mbvdw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-017811-w38mbvdw.txt' === file2bib.sh === id: cord-352492-6ihyiwgb author: Eickmann, Markus title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively date: 2018-05-06 pages: extension: .txt txt: ./txt/cord-352492-6ihyiwgb.txt cache: ./cache/cord-352492-6ihyiwgb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-352492-6ihyiwgb.txt' === file2bib.sh === id: cord-001513-p7v5p036 author: Ekins, Sean title: A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus date: 2014-12-12 pages: extension: .txt txt: ./txt/cord-001513-p7v5p036.txt cache: ./cache/cord-001513-p7v5p036.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-001513-p7v5p036.txt' === file2bib.sh === id: cord-274377-57zy6unz author: Long, Jason title: Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry date: 2015-02-10 pages: extension: .txt txt: ./txt/cord-274377-57zy6unz.txt cache: ./cache/cord-274377-57zy6unz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-274377-57zy6unz.txt' === file2bib.sh === id: cord-344316-mwnnmwnw author: Herst, C.V. title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-344316-mwnnmwnw.txt cache: ./cache/cord-344316-mwnnmwnw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-344316-mwnnmwnw.txt' === file2bib.sh === id: cord-325423-d212h4bp author: Carrion, Ricardo title: A small nonhuman primate model for filovirus-induced disease date: 2011-11-01 pages: extension: .txt txt: ./txt/cord-325423-d212h4bp.txt cache: ./cache/cord-325423-d212h4bp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-325423-d212h4bp.txt' === file2bib.sh === id: cord-002185-oz7hras7 author: Nelson, Elizabeth A. title: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date: 2016-08-02 pages: extension: .txt txt: ./txt/cord-002185-oz7hras7.txt cache: ./cache/cord-002185-oz7hras7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002185-oz7hras7.txt' === file2bib.sh === id: cord-001764-njzyu4mv author: Hofmann-Winkler, Heike title: Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976 date: 2015-10-01 pages: extension: .txt txt: ./txt/cord-001764-njzyu4mv.txt cache: ./cache/cord-001764-njzyu4mv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001764-njzyu4mv.txt' === file2bib.sh === id: cord-300133-yc2wxgid author: Martínez, Miguel J. title: Ebola Virus Infection: Overview and Update on Prevention and Treatment date: 2015-09-12 pages: extension: .txt txt: ./txt/cord-300133-yc2wxgid.txt cache: ./cache/cord-300133-yc2wxgid.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-300133-yc2wxgid.txt' === file2bib.sh === id: cord-318587-ewvnkdr2 author: Steeds, Kimberley title: Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date: 2020-08-31 pages: extension: .txt txt: ./txt/cord-318587-ewvnkdr2.txt cache: ./cache/cord-318587-ewvnkdr2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-318587-ewvnkdr2.txt' === file2bib.sh === id: cord-334560-1j9zmuub author: Hunt, Catherine L. title: Filovirus Entry: A Novelty in the Viral Fusion World date: 2012-02-07 pages: extension: .txt txt: ./txt/cord-334560-1j9zmuub.txt cache: ./cache/cord-334560-1j9zmuub.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-334560-1j9zmuub.txt' === file2bib.sh === id: cord-004069-nuep8nim author: DeWald, Lisa Evans title: In Vivo Activity of Amodiaquine against Ebola Virus Infection date: 2019-12-27 pages: extension: .txt txt: ./txt/cord-004069-nuep8nim.txt cache: ./cache/cord-004069-nuep8nim.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004069-nuep8nim.txt' === file2bib.sh === id: cord-350083-kldu8q8x author: Oany, Arafat Rahman title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach date: 2015-08-08 pages: extension: .txt txt: ./txt/cord-350083-kldu8q8x.txt cache: ./cache/cord-350083-kldu8q8x.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-350083-kldu8q8x.txt' === file2bib.sh === id: cord-272576-ez731lif author: Wada, Yoshiko title: Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date: 2016-11-03 pages: extension: .txt txt: ./txt/cord-272576-ez731lif.txt cache: ./cache/cord-272576-ez731lif.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-272576-ez731lif.txt' === file2bib.sh === id: cord-276437-5gkdotvt author: Liu, William J. title: Intra-host Ebola viral adaption during human infection date: 2019-02-20 pages: extension: .txt txt: ./txt/cord-276437-5gkdotvt.txt cache: ./cache/cord-276437-5gkdotvt.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-276437-5gkdotvt.txt' === file2bib.sh === id: cord-279152-yh7x7w2q author: Ndungo, Esther title: A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles date: 2016-03-30 pages: extension: .txt txt: ./txt/cord-279152-yh7x7w2q.txt cache: ./cache/cord-279152-yh7x7w2q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-279152-yh7x7w2q.txt' === file2bib.sh === id: cord-002463-qhtj1pef author: Dash, Raju title: In silico-based vaccine design against Ebola virus glycoprotein date: 2017-03-21 pages: extension: .txt txt: ./txt/cord-002463-qhtj1pef.txt cache: ./cache/cord-002463-qhtj1pef.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002463-qhtj1pef.txt' === file2bib.sh === id: cord-003917-bswndfvk author: Lalle, Eleonora title: Pulmonary Involvement during the Ebola Virus Disease date: 2019-08-24 pages: extension: .txt txt: ./txt/cord-003917-bswndfvk.txt cache: ./cache/cord-003917-bswndfvk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003917-bswndfvk.txt' === file2bib.sh === id: cord-284791-bgodmbru author: Whitworth, Carrie title: Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-284791-bgodmbru.txt cache: ./cache/cord-284791-bgodmbru.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-284791-bgodmbru.txt' === file2bib.sh === id: cord-001546-ndz3oarf author: Ayithan, Natarajan title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 pages: extension: .txt txt: ./txt/cord-001546-ndz3oarf.txt cache: ./cache/cord-001546-ndz3oarf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-001546-ndz3oarf.txt' === file2bib.sh === id: cord-346267-l08ld2cy author: Wertheim, Joel O. title: Purifying Selection Can Obscure the Ancient Age of Viral Lineages date: 2011-06-24 pages: extension: .txt txt: ./txt/cord-346267-l08ld2cy.txt cache: ./cache/cord-346267-l08ld2cy.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-346267-l08ld2cy.txt' === file2bib.sh === id: cord-289413-mbrw85og author: Flego, Michela title: Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity date: 2019-09-05 pages: extension: .txt txt: ./txt/cord-289413-mbrw85og.txt cache: ./cache/cord-289413-mbrw85og.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-289413-mbrw85og.txt' === file2bib.sh === id: cord-002013-rb9xdzro author: Zheng, Xuexing title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date: 2016-04-12 pages: extension: .txt txt: ./txt/cord-002013-rb9xdzro.txt cache: ./cache/cord-002013-rb9xdzro.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-002013-rb9xdzro.txt' === file2bib.sh === id: cord-102206-mb0qcd0b author: Seymour, Elif title: Configurable Digital Virus Counter on Robust Universal DNA Chips date: 2020-10-22 pages: extension: .txt txt: ./txt/cord-102206-mb0qcd0b.txt cache: ./cache/cord-102206-mb0qcd0b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-102206-mb0qcd0b.txt' === file2bib.sh === id: cord-327641-hqnem2zs author: Ji, Ying-Jie title: Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone date: 2016-11-03 pages: extension: .txt txt: ./txt/cord-327641-hqnem2zs.txt cache: ./cache/cord-327641-hqnem2zs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-327641-hqnem2zs.txt' === file2bib.sh === id: cord-303647-c4umbcvn author: Reed, Patricia E. title: A New Approach for Monitoring Ebolavirus in Wild Great Apes date: 2014-09-18 pages: extension: .txt txt: ./txt/cord-303647-c4umbcvn.txt cache: ./cache/cord-303647-c4umbcvn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-303647-c4umbcvn.txt' === file2bib.sh === id: cord-335093-tc1qo2k0 author: Gehring, Gerrit title: The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry date: 2014-08-01 pages: extension: .txt txt: ./txt/cord-335093-tc1qo2k0.txt cache: ./cache/cord-335093-tc1qo2k0.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-335093-tc1qo2k0.txt' === file2bib.sh === id: cord-002676-zwkl1ywk author: Yu, Dong-Shan title: The lifecycle of the Ebola virus in host cells date: 2017-06-15 pages: extension: .txt txt: ./txt/cord-002676-zwkl1ywk.txt cache: ./cache/cord-002676-zwkl1ywk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002676-zwkl1ywk.txt' === file2bib.sh === id: cord-003859-k8wfyj9b author: Paweska, Janusz T. title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date: 2019-07-24 pages: extension: .txt txt: ./txt/cord-003859-k8wfyj9b.txt cache: ./cache/cord-003859-k8wfyj9b.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003859-k8wfyj9b.txt' === file2bib.sh === id: cord-004126-u6ts87ur author: Furuyama, Wakako title: A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades date: 2020-01-10 pages: extension: .txt txt: ./txt/cord-004126-u6ts87ur.txt cache: ./cache/cord-004126-u6ts87ur.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-004126-u6ts87ur.txt' === file2bib.sh === id: cord-297082-2rhoffx2 author: Yu, Changqing title: MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date: 2020-09-15 pages: extension: .txt txt: ./txt/cord-297082-2rhoffx2.txt cache: ./cache/cord-297082-2rhoffx2.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-297082-2rhoffx2.txt' === file2bib.sh === id: cord-002935-jq1xumrh author: Postnikova, Elena title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date: 2018-03-22 pages: extension: .txt txt: ./txt/cord-002935-jq1xumrh.txt cache: ./cache/cord-002935-jq1xumrh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002935-jq1xumrh.txt' === file2bib.sh === id: cord-350565-mejd7blb author: Lewnard, Joseph A title: Emerging Challenges and Opportunities in Infectious Disease Epidemiology date: 2019-03-16 pages: extension: .txt txt: ./txt/cord-350565-mejd7blb.txt cache: ./cache/cord-350565-mejd7blb.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-350565-mejd7blb.txt' === file2bib.sh === id: cord-002500-9p2n8tjx author: Lambe, Teresa title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? date: 2017-05-26 pages: extension: .txt txt: ./txt/cord-002500-9p2n8tjx.txt cache: ./cache/cord-002500-9p2n8tjx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-002500-9p2n8tjx.txt' === file2bib.sh === id: cord-004335-bw3tziup author: Perez-Zsolt, Daniel title: When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date: 2019-12-19 pages: extension: .txt txt: ./txt/cord-004335-bw3tziup.txt cache: ./cache/cord-004335-bw3tziup.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-004335-bw3tziup.txt' === file2bib.sh === id: cord-296399-vvbjulm9 author: Brinkmann, Constantin title: The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date: 2017-12-07 pages: extension: .txt txt: ./txt/cord-296399-vvbjulm9.txt cache: ./cache/cord-296399-vvbjulm9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-296399-vvbjulm9.txt' === file2bib.sh === id: cord-003779-5yhoiv76 author: Singleton, Courtney D. title: Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry date: 2019-07-17 pages: extension: .txt txt: ./txt/cord-003779-5yhoiv76.txt cache: ./cache/cord-003779-5yhoiv76.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-003779-5yhoiv76.txt' === file2bib.sh === id: cord-000547-adfigzc1 author: Beniac, Daniel R. title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date: 2012-01-11 pages: extension: .txt txt: ./txt/cord-000547-adfigzc1.txt cache: ./cache/cord-000547-adfigzc1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000547-adfigzc1.txt' === file2bib.sh === id: cord-284845-on97zu6w author: Falcinelli, Shane D. title: Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections date: 2016-07-29 pages: extension: .txt txt: ./txt/cord-284845-on97zu6w.txt cache: ./cache/cord-284845-on97zu6w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-284845-on97zu6w.txt' === file2bib.sh === id: cord-337998-08tknscm author: Sztuba-Solinska, Joanna title: A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8 date: 2016-11-16 pages: extension: .txt txt: ./txt/cord-337998-08tknscm.txt cache: ./cache/cord-337998-08tknscm.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 7 resourceName b'cord-337998-08tknscm.txt' === file2bib.sh === id: cord-330647-w1bpeqzg author: Wong, Samson Sai-Yin title: Ebola virus disease in nonendemic countries date: 2015-05-31 pages: extension: .txt txt: ./txt/cord-330647-w1bpeqzg.txt cache: ./cache/cord-330647-w1bpeqzg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-330647-w1bpeqzg.txt' === file2bib.sh === id: cord-256187-ofp7tupv author: Kühl, A. title: How Ebola Virus Counters the Interferon System date: 2012-09-07 pages: extension: .txt txt: ./txt/cord-256187-ofp7tupv.txt cache: ./cache/cord-256187-ofp7tupv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-256187-ofp7tupv.txt' === file2bib.sh === id: cord-305653-f9vqn96o author: Schmidt, Rebecca title: Generation of therapeutic antisera for emerging viral infections date: 2018-10-05 pages: extension: .txt txt: ./txt/cord-305653-f9vqn96o.txt cache: ./cache/cord-305653-f9vqn96o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-305653-f9vqn96o.txt' === file2bib.sh === id: cord-011129-btaxvmsr author: Di Paola, Nicholas title: Viral genomics in Ebola virus research date: 2020-05-04 pages: extension: .txt txt: ./txt/cord-011129-btaxvmsr.txt cache: ./cache/cord-011129-btaxvmsr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-011129-btaxvmsr.txt' === file2bib.sh === id: cord-293481-bmfj50fb author: Malin, Jakob J. title: Remdesivir against COVID-19 and Other Viral Diseases date: 2020-10-14 pages: extension: .txt txt: ./txt/cord-293481-bmfj50fb.txt cache: ./cache/cord-293481-bmfj50fb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-293481-bmfj50fb.txt' === file2bib.sh === id: cord-355737-o0y4rn0z author: Ng, Melinda title: Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats date: 2015-12-23 pages: extension: .txt txt: ./txt/cord-355737-o0y4rn0z.txt cache: ./cache/cord-355737-o0y4rn0z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-355737-o0y4rn0z.txt' === file2bib.sh === id: cord-288734-xinkqs6u author: Muñoz-Fontela, César title: Ebola Virus Disease in Humans: Pathophysiology and Immunity date: 2017-03-30 pages: extension: .txt txt: ./txt/cord-288734-xinkqs6u.txt cache: ./cache/cord-288734-xinkqs6u.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-288734-xinkqs6u.txt' === file2bib.sh === id: cord-342052-v4y1xc90 author: Horigan, Verity title: Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States date: 2017-10-02 pages: extension: .txt txt: ./txt/cord-342052-v4y1xc90.txt cache: ./cache/cord-342052-v4y1xc90.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-342052-v4y1xc90.txt' === file2bib.sh === id: cord-001542-f089bs8r author: Lai, Kang Yiu title: Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date: 2014-11-28 pages: extension: .txt txt: ./txt/cord-001542-f089bs8r.txt cache: ./cache/cord-001542-f089bs8r.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001542-f089bs8r.txt' === file2bib.sh === id: cord-294342-7ycgd0h7 author: Markosyan, Ruben M. title: Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date: 2016-01-05 pages: extension: .txt txt: ./txt/cord-294342-7ycgd0h7.txt cache: ./cache/cord-294342-7ycgd0h7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-294342-7ycgd0h7.txt' === file2bib.sh === id: cord-354068-4qlk6y7h author: Friedrich, Brian M. title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date: 2012-09-21 pages: extension: .txt txt: ./txt/cord-354068-4qlk6y7h.txt cache: ./cache/cord-354068-4qlk6y7h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-354068-4qlk6y7h.txt' === file2bib.sh === id: cord-000804-0hlj6r10 author: Brauburger, Kristina title: Forty-Five Years of Marburg Virus Research date: 2012-10-01 pages: extension: .txt txt: ./txt/cord-000804-0hlj6r10.txt cache: ./cache/cord-000804-0hlj6r10.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.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-000804-0hlj6r10.txt' Que is empty; done keyword-ebov-cord === reduce.pl bib === id = cord-002013-rb9xdzro author = Zheng, Xuexing title = Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date = 2016-04-12 pages = extension = .txt mime = text/plain words = 6027 sentences = 286 flesch = 56 summary = To investigate whether EBOV infections can be controlled by virus neutralization alone, and to prevent the possible induction of serum sickness in humans that would be administered antisera, the post-exposure efficacy of F(ab′ ) 2 (immunoglobulin treated with pepsin to remove the Fc regions of the antibody) were also investigated side-by-side with equine antisera in all experiments as a potential alternate treatment. Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints ( Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP. The observation that administering F(ab′ ) 2 at 1 dpi is more efficacious than when the same treatment was given at 30 minutes post-exposure (Fig. 5A ) was also observed in past studies with therapeutic EBOV GP-specific monoclonal antibodies 25, 26 , and suggests that virus neutralization may play a bigger role in protection at a later timepoint after EBOV challenge. cache = ./cache/cord-002013-rb9xdzro.txt txt = ./txt/cord-002013-rb9xdzro.txt === reduce.pl bib === id = cord-002676-zwkl1ywk author = Yu, Dong-Shan title = The lifecycle of the Ebola virus in host cells date = 2017-06-15 pages = extension = .txt mime = text/plain words = 5322 sentences = 287 flesch = 45 summary = However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. Then, the Tyro3 protein kinase (TAM) family, including Axl, Dtk, and Mer, which widely expressed in many cell types, span the plasma membrane and contain intracellular tyrosine kinase domains, are facilitate EBOV GP-dependent attachment [39, 40] . In addition, folate receptor-α (FR-α) was reported to be a co-receptor in binding cells that expressed MARV or EBOV GP, mediated syncytia formation triggered by GP, and facilitated cellular entry of the virus [28] . After the virus has been internalized into the endosome, fusion induced by cleaved GP is fundamentally independent of pH, which indicated an unidentified host cell factor critical for filovirus entry is sensitive to an acidic pH [56] . Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus cache = ./cache/cord-002676-zwkl1ywk.txt txt = ./txt/cord-002676-zwkl1ywk.txt === reduce.pl bib === id = cord-001764-njzyu4mv author = Hofmann-Winkler, Heike title = Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976 date = 2015-10-01 pages = extension = .txt mime = text/plain words = 4175 sentences = 202 flesch = 49 summary = Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. However, EBOV-GP 2014 was less susceptible than EBOV-GP 1976 to blockade by a third inhibitor, CatL ( Figure 3B ), which inhibits catB and catL activity to similar extents [40] , suggesting subtle differences in the protease dependence of these GPs. HIV-derived particles rapidly lose infectivity when stored at room temperature [41] , and this loss might be due to inactivation of the viral envelope protein. Comparably Inhibited by IFITM Proteins and Neutralizing Antibody KZ52 IFITM proteins 1, 2, and 3 inhibit cellular entry of EBOV [42] and several other viral pathogens [42, 43] and might reduce EBOV amplification in the infected host, raising the question of whether viruses circulating in 2014 are less susceptible to IFITM protein inhibition than those responsible for the 1976 outbreak in Zaire. cache = ./cache/cord-001764-njzyu4mv.txt txt = ./txt/cord-001764-njzyu4mv.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-001546-ndz3oarf author = Ayithan, Natarajan title = Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date = 2015-02-26 pages = extension = .txt mime = text/plain words = 5128 sentences = 298 flesch = 52 summary = Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. cache = ./cache/cord-001546-ndz3oarf.txt txt = ./txt/cord-001546-ndz3oarf.txt === reduce.pl bib === id = cord-274377-57zy6unz author = Long, Jason title = Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry date = 2015-02-10 pages = extension = .txt mime = text/plain words = 3938 sentences = 205 flesch = 54 summary = To this end we re-examined the anti-viral properties of CQ, and show here that it inhibited the pH-dependent endosomal entry of a pseudotyped virus (PV) bearing EBOV glycoproteins, in the same way as did the potent and specific vacuolar-ATPase (vATPase) inhibitor bafilyomycin A1 (BafA1) (a non-medical laboratory compound). We also show that licensed and widely used proton pump inhibitors (PPIs) for treatment of gastric acid reflux, omeprazole (OM) and esomeprazole (ESOM), inhibited PV EBOV entry, likely by their off-target inhibitory activity on endosomal vATPase. In this instance, a 'fusion inhibitor' could target the host cell machinery preventing acidification of the endosome, working to inhibit virus entry of several different viruses. Given the volume of research suggesting these off target effects depend on an ability to affect intracellular pH, we hypothesised that these drugs would, like CQ and BafA1, inhibit EBOV, MARV and influenza virus pH dependent entry. cache = ./cache/cord-274377-57zy6unz.txt txt = ./txt/cord-274377-57zy6unz.txt === reduce.pl bib === id = cord-296517-414grqif author = Wong, Gary title = MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease date = 2015-10-14 pages = extension = .txt mime = text/plain words = 2880 sentences = 129 flesch = 50 summary = In September 2012, Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged as a novel virus that can result in severe respiratory disease with renal failure, with a case fatality rate of up to 38%. Notably, between May and July 2015, an outbreak of MERS-CoV centered in South Korea killed 36 people out of 186 confirmed cases (Promedmail.org, 2015) , with thousands quarantined as health authorities attempted to control virus spread. The 2015 MERS-CoV outbreak in South Korea began from an imported case, a 68-year-old male with a recent travel history to several Middle Eastern countries, including Bahrain, the United Arab Emirates, Saudi Arabia, and Qatar. Thus, the MERS-CoV outbreak in South Korea was driven primarily by three infected individuals, and approximately 75% of cases can be traced back to three super-spreaders who have each infected a disproportionately high number of contacts ( Figure 1A ). cache = ./cache/cord-296517-414grqif.txt txt = ./txt/cord-296517-414grqif.txt === reduce.pl bib === id = cord-011129-btaxvmsr author = Di Paola, Nicholas title = Viral genomics in Ebola virus research date = 2020-05-04 pages = extension = .txt mime = text/plain words = 9440 sentences = 433 flesch = 37 summary = Here, we review how recent advances in genomic technologies have shaped past and current responses to outbreaks of Ebola virus disease (EVD), including insights into filovirus diversity and evolution. After this identification, considerations other than sequencing speed (for example, sequencing accuracy and processivity) become paramount in determining virus transmission networks and in detecting changes in the viral genome (between cases in the current outbreak and between the current and previous outbreaks) that could subvert MCMs. However, whereas unbiased sequencing approaches using high fidelity platforms can lead to the discovery of co-infections and reveal important clinical considerations during the treatment of patients near the point of need, targeted methods of pathogen characterization using the portable sequencing platforms iSeq 100 and MiSeq (which use bait-enrichment techniques) and MinION (which uses amplicon sequencing) can still provide useful genomic data albeit with a lower sequencing output (that is, a lower number of reads) than unbiased sequencing. cache = ./cache/cord-011129-btaxvmsr.txt txt = ./txt/cord-011129-btaxvmsr.txt === reduce.pl bib === id = cord-284845-on97zu6w author = Falcinelli, Shane D. title = Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections date = 2016-07-29 pages = extension = .txt mime = text/plain words = 8473 sentences = 421 flesch = 35 summary = Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. As emerging viral infections often result in severe illness including respiratory failure [severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza] and multiorgan failure [Ebola virus disease (EVD)], understanding complex pathogenesis of these infections is required for effective vaccine and therapeutic design and for improved patient care. Specifically, detailed natural history studies merging multiple data streams including OMICS approaches (high-throughput gene expression and kinomics) and focused translational investigations utilizing relevant models that can be validated to human disease are needed to clarify disease pathogenesis, advance therapeutic discovery, and facilitate regulatory approval. cache = ./cache/cord-284845-on97zu6w.txt txt = ./txt/cord-284845-on97zu6w.txt === reduce.pl bib === id = cord-300133-yc2wxgid author = Martínez, Miguel J. title = Ebola Virus Infection: Overview and Update on Prevention and Treatment date = 2015-09-12 pages = extension = .txt mime = text/plain words = 4302 sentences = 243 flesch = 50 summary = In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Over the past 17 months, the West Africa EVD outbreak has provided an important opportunity to consider use of and evaluate several therapeutic and prophylactic agents (e.g., vaccines) to determine their safety and efficacy [5, 6] . FGI-103, FGI-104, and FGI-106 are a group of broad-spectrum antiviral agents that inhibit viral replication in a dose-dependent manner among multiple and genetically distinct viruses including EBOV, bunyaviruses, dengue virus, Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an emprical treatment during outbreaks cache = ./cache/cord-300133-yc2wxgid.txt txt = ./txt/cord-300133-yc2wxgid.txt === reduce.pl bib === id = cord-000547-adfigzc1 author = Beniac, Daniel R. title = The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date = 2012-01-11 pages = extension = .txt mime = text/plain words = 7782 sentences = 392 flesch = 51 summary = METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes ( Figure 5 ) to a resolution of 14 Å as measured by the Fourier Shell Correlation (FSC) 0.5 criterion. Analysis of 2090 distinct intact virions with a nucleocapsid from cryo-electron micrographs shows that the most common class length (53%) of virus particles is 982679 nm ( Figure 1A , Table S1 ). cache = ./cache/cord-000547-adfigzc1.txt txt = ./txt/cord-000547-adfigzc1.txt === reduce.pl bib === id = cord-004335-bw3tziup author = Perez-Zsolt, Daniel title = When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date = 2019-12-19 pages = extension = .txt mime = text/plain words = 7360 sentences = 388 flesch = 40 summary = Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. Thus, infection with viruses such as HIV-1 or EBOV tightly upregulates Siglec-1 expression on APCs, as they directly trigger or indirectly promote the release of type I IFNs via immune activating factors (Figure 1 ). Thus, HIV-1 and EBOV infections trigger an immune activation state that upregulates Siglec-1 expression on DCs, a situation that might favor early viral dissemination events in an otherwise antiviral environment [80] . cache = ./cache/cord-004335-bw3tziup.txt txt = ./txt/cord-004335-bw3tziup.txt === reduce.pl bib === id = cord-001513-p7v5p036 author = Ekins, Sean title = A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus date = 2014-12-12 pages = extension = .txt mime = text/plain words = 4756 sentences = 250 flesch = 56 summary = Common features pharmacophore for EBOV actives Two papers from 2013 described compounds active as inhibitors of different EBOV strains in vitro and in vivo, namely amodiaquine and chloroquine in one study 8 , clomiphene and toremifene in another 9 . These suggest that the receptor-ligand based approach results in a general similarity across the nine structures, likely indicating the similar binding mode and importance of features for interfering with this generally hydrophobic pocket for protein-protein interactions. In silico docking of molecules in VP35 structure Redocking the 4IBI ligand in the protein resulted in an RMSD of 3.02Å, which generally indicates the difficulty of predicting orientations for compounds binding in what is a relatively hydrophobic and shallow pocket ( Figure S1 ). Pharmacophores, receptor ligand models and docking data for FDA-approved drugs inhibiting the Ebola virus, 10.5256/f1000research.5741.d38449 35 . cache = ./cache/cord-001513-p7v5p036.txt txt = ./txt/cord-001513-p7v5p036.txt === reduce.pl bib === id = cord-002935-jq1xumrh author = Postnikova, Elena title = Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date = 2018-03-22 pages = extension = .txt mime = text/plain words = 6226 sentences = 315 flesch = 56 summary = Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate. The CELIA was compared to the fluorescent assay (detected by regular plate reader or the HCI system) by testing the efficacy of toremifene citrate against EBOV infection in Huh 7 cells with a range of MOIs (0.1, 0.3, 1, and 3 ) at three different time points (24, 48 and 72 hpi) . The established CELIA was used to compare anti-EBOV activity of toremifene citrate in 3 different cell types, Vero E6, Huh 7 and MDMs using an MOI of 0.5 and a time point of 48 h (Fig 7) . cache = ./cache/cord-002935-jq1xumrh.txt txt = ./txt/cord-002935-jq1xumrh.txt === reduce.pl bib === id = cord-000804-0hlj6r10 author = Brauburger, Kristina title = Forty-Five Years of Marburg Virus Research date = 2012-10-01 pages = extension = .txt mime = text/plain words = 14922 sentences = 730 flesch = 45 summary = While the ectodomain, which is mainly formed by GP 1 , mediates binding to entry factors and receptors [87] [88] [89] [90] [91] [92] [93] [94] [95] , the transmembrane subunit GP 2 contains the fusion peptide and is presumed to mediate fusion of the viral and the cellular membrane based on similarity to EBOV GP 2 both at the amino acid and structural level [96, 97] . The IFN-inducible antiviral protein tetherin was shown to block the release of VP40-induced virus-like MARV and EBOV particles, suggesting that tetherin might act as a restriction factor for filovirus release [102, 103] . After the nucleocapsid is released into the cytoplasm of the infected cell, transcription and replication of the viral RNA genome takes place (Figure 7 ). Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections cache = ./cache/cord-000804-0hlj6r10.txt txt = ./txt/cord-000804-0hlj6r10.txt === reduce.pl bib === id = cord-293481-bmfj50fb author = Malin, Jakob J. title = Remdesivir against COVID-19 and Other Viral Diseases date = 2020-10-14 pages = extension = .txt mime = text/plain words = 9097 sentences = 428 flesch = 42 summary = Remdesivir or GS-5734 is a prodrug of a nucleoside analog with direct antiviral activity against several single-stranded RNA viruses, including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, preliminary data from a randomized placebo-controlled clinical trial showed that remdesivir reduces the time to recovery in patients with COVID-19 (5) , leading to an emergency-use authorization (EUA) by the U.S. Food and Drug Administration (FDA) only 2 days after the first press release from the National Institute of Allergy and Infectious Diseases (NIAID) (6) . There were strong arguments for the antiviral effect of remdesivir against coronaviruses emerging from multiple cell-based in vitro models, including primary human airway epithelial (HAE) cell cultures (25) , and, for MERS-CoV, from a mouse model of pulmonary infection (28) . After the outbreak of SARS-CoV-2 in January 2020, remdesivir was rapidly tested in a Vero E6 cell-based model that made use of direct viral quantification by rtPCR along with the antimalaria and immune-modulating drug chloroquine and known antivirals such as ribavirin and penciclovir. cache = ./cache/cord-293481-bmfj50fb.txt txt = ./txt/cord-293481-bmfj50fb.txt === reduce.pl bib === id = cord-288029-6l91knu3 author = Elfiky, Abdo A. title = Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction date = 2020-04-14 pages = extension = .txt mime = text/plain words = 3082 sentences = 206 flesch = 65 summary = title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction In this study, structural and sequence analysis and molecular docking are used to predict the possible binding site between the cell-surface HSPA5 and EBOV GP1. In this work, the binding site between cell-surface HSPA5 and viral GP1 protein is predicted based on sequence, and thus, Pep42 is an example of a class of drugs that may reduce EBOV infections. In addition, HPEPDOCK constructs different possible conformations of the peptide and tests the binding affinity of each of the predicted structures against the target protein (Zhou et al. The cyclic peptide Pep42 was reported to selectively target cell-surface HSPA5 (which appears in some types of cancer) and used as a drug carrier for the anti-cancer agent, doxorubicin (Ibrahim et al. These hydrophobic residues of EBOV GP1 (C121, L122, A124, A125, I129, F132, and C135) are suggested to be the binding site for cell-surface HSPA5. Ebola virus glycoprotein GP1-host cell-surface HSPA5 binding site prediction cache = ./cache/cord-288029-6l91knu3.txt txt = ./txt/cord-288029-6l91knu3.txt === reduce.pl bib === id = cord-002185-oz7hras7 author = Nelson, Elizabeth A. title = Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date = 2016-08-02 pages = extension = .txt mime = text/plain words = 5047 sentences = 249 flesch = 52 summary = In this system, 4-hydroxy-zuclomiphene appeared more potent than the Our previous findings indicated that clomiphene blocks EBOV infection by blocking entry of viral particles into the cell cytoplasm [20, 29] ; this effect appears to be at the level of fusion between the membrane of the viral particle and the limiting membrane of an Niemann-Pick disease, type C1 positive (NPC1 + ) endolysosome, the site of EBOV fusion [30] [31] [32] . Similar results were seen when comparing eight doses of clomiphene and zuclomiphene in trVLP infection ( Figure 5A ) and VLP entry ( Figure 5B ) assays. Where tested, they were equally effective to each other in two cell types and for entry mediated by three filoviral GPs. 4-hydroxy-enclomiphene, and 4-hydroxy-zuclomiphene also blocked EBOV trVLP infection and VLP entry under the cache = ./cache/cord-002185-oz7hras7.txt txt = ./txt/cord-002185-oz7hras7.txt === reduce.pl bib === id = cord-002500-9p2n8tjx author = Lambe, Teresa title = A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? date = 2017-05-26 pages = extension = .txt mime = text/plain words = 7327 sentences = 288 flesch = 38 summary = The other vaccine modality being assessed as an Ebola vaccine candidate is the recombinant vesicular stomatitis virus encoding EBOV glycoprotein (rVSV-ZEBOV), which is an attenuated replication-competent viral vector. In the absence of any gold standard for measuring humoral immunity against Ebola virus, a wide variety of assays were used to evaluate antibody responses to vaccines during the recent EVD outbreak. Many of the other binding assays used in these Phase I trials correlate strongly and, in particular, it is useful that the standardized glycoprotein ELISA and pseudotyped lentivirus assays each correlate strongly with neutralizing titres against live Ebola virus as these assays avoid the need to work at high containment levels, but may be used to indicate the presence of antibodies with neutralizing activity. In a pre-clinical NHP model, IgG responses after immunization with AdHu5-based Ebola virus vaccines were measured using an ELISA against GP, where 100% protection against a lethal challenge was predicted by titres of 3700 or greater, while a titre of around 2000 predicted 85% survival. cache = ./cache/cord-002500-9p2n8tjx.txt txt = ./txt/cord-002500-9p2n8tjx.txt === reduce.pl bib === id = cord-344316-mwnnmwnw author = Herst, C.V. title = An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design date = 2020-04-28 pages = extension = .txt mime = text/plain words = 3495 sentences = 194 flesch = 49 summary = title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors' CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. Wilson We set out to see if we could drive CTL expansion directed against NP43-53 to occur after vaccinating C57BL/6 mice with Ebola Zaire NP43-53 (VYQVNNLEEIC), 50 and to subsequently conduct an in-vivo EBOV challenge study to see if this peptide was protective. We show here that the H2-D b restricted epitopes VSV (RGYVYQGL) and OVA (SIINFEKL), when administered to C57BL/6 mice, each produce a CD8+ We used this adjuvanted microsphere peptide vaccine platform to immunize C57BL/6 mice with NP43-53, the CTL+ class I peptide antigen from the Ebola Ziare NP protein identified as protective by Wilson et al. cache = ./cache/cord-344316-mwnnmwnw.txt txt = ./txt/cord-344316-mwnnmwnw.txt === reduce.pl bib === id = cord-279152-yh7x7w2q author = Ndungo, Esther title = A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles date = 2016-03-30 pages = extension = .txt mime = text/plain words = 5230 sentences = 243 flesch = 49 summary = Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. We also found that NPC1 could influence the cellular host range of filoviruses-human NPC1 conferred susceptibility to filovirus entry and infection when expressed in the nonpermissive reptilian cell line VH-2, derived from a Russell's viper (Daboia russellii) (22) . These findings provide additional evidence that NPC1-encoded residue 503 influences the cellular host range of EBOV at the level of virus-receptor recognition and raise the possibility that sequence differences at this position influence the susceptibility of reptiles to filovirus infection in nature. cache = ./cache/cord-279152-yh7x7w2q.txt txt = ./txt/cord-279152-yh7x7w2q.txt === reduce.pl bib === id = cord-276437-5gkdotvt author = Liu, William J. title = Intra-host Ebola viral adaption during human infection date = 2019-02-20 pages = extension = .txt mime = text/plain words = 5115 sentences = 251 flesch = 54 summary = EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Recent studies also showed that, during the epidemic, the EBOV isolates from early in the outbreak with amino acid substitutions in the GP protein possessed increased tropism for human cells, indicating human adaptation of Ebola virus during human-to-human transmission [19] [20] [21] . In a single patient, genome sequences obtained from samples during earlier stages of the acute infection phase possessed Ts at the 13 TNC positions, whereas Cs were found from samples collected during the recovery process. Our data indicate that short stretches of TNC substitutions are part of the convergent evolution during the infection process of EVD patients, shedding light on the dynamic intra-host genomic variation of EBOV during the 2013-2016 epidemic. cache = ./cache/cord-276437-5gkdotvt.txt txt = ./txt/cord-276437-5gkdotvt.txt === reduce.pl bib === id = cord-289413-mbrw85og author = Flego, Michela title = Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity date = 2019-09-05 pages = extension = .txt mime = text/plain words = 5528 sentences = 243 flesch = 47 summary = RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. This study reports the selection by phage display and characterization of 5 different human scFv antibodies binding to an active form of the Zaire EBOV VP35 [24, 25] . In a competitive assay, ELISA plates coated with VP35 or with the control antigen GO were blocked; they were then incubated with purified scFv-expressing phage both in the absence and in the presence of the competitor soluble non-phage-fused scFv at the maximum concentration of 500 μg/ml. cache = ./cache/cord-289413-mbrw85og.txt txt = ./txt/cord-289413-mbrw85og.txt === reduce.pl bib === id = cord-004126-u6ts87ur author = Furuyama, Wakako title = A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades date = 2020-01-10 pages = extension = .txt mime = text/plain words = 6034 sentences = 333 flesch = 51 summary = Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine. We found that a single vaccination with VSV-vectors expressing the full-length HA (HAfl) induced crossreactive H5-specific antibodies and conferred complete protection against lethal challenge with various H5 clade 2 viruses. In contrast to all the sHA-based vaccines, single doses of the VSV-EBOV-HAfl or VSV-HAfl vectors were sufficient to provide complete protection from lethal homologous H5N1 challenge in mice (Fig. 2) . However, this study did not provide any data supporting an advantage of including VSV-EBOV as part of the vector design over just expressing VSV-HAfl as both vectors performed similarly well with no statistically significant difference in efficacy following single-dose or prime/boost administration (Fig. 2 ) nor in antibody responses (Fig. 3, Table 1 ). cache = ./cache/cord-004126-u6ts87ur.txt txt = ./txt/cord-004126-u6ts87ur.txt === reduce.pl bib === id = cord-004069-nuep8nim author = DeWald, Lisa Evans title = In Vivo Activity of Amodiaquine against Ebola Virus Infection date = 2019-12-27 pages = extension = .txt mime = text/plain words = 5707 sentences = 288 flesch = 53 summary = A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 . cache = ./cache/cord-004069-nuep8nim.txt txt = ./txt/cord-004069-nuep8nim.txt === reduce.pl bib === id = cord-318587-ewvnkdr2 author = Steeds, Kimberley title = Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date = 2020-08-31 pages = extension = .txt mime = text/plain words = 4973 sentences = 244 flesch = 46 summary = We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The aim of this study was to assess the suitability of EBOV GP pseudotyped HIV-1 and VSV systems to measure neutralisation by EVD survivor plasma, in comparison with results from a live EBOV neutralisation assay. To determine the optimal pseudotyped virus input to use in the HIV-and VSV-based assays, neutralisation of different amounts of the EBOV GP pseudotyped viruses by plasma from a Guinean EVD survivor donor or human anti-EBOV GP mAb KZ52 was assessed. When IC 50 values of EBOV GP pseudotyped HIV-1 neutralisation of the 30 EVD survivor and 10 negative plasma samples were compared with GMT values for the live EBOV neutralisation assay, a positive correlation (r s = 0.54) was determined using the nonparametric Spearman correlation coefficient (Fig. 5a) and this was statistically significant (p = 0.0004). cache = ./cache/cord-318587-ewvnkdr2.txt txt = ./txt/cord-318587-ewvnkdr2.txt === reduce.pl bib === id = cord-003779-5yhoiv76 author = Singleton, Courtney D. title = Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry date = 2019-07-17 pages = extension = .txt mime = text/plain words = 8976 sentences = 434 flesch = 48 summary = Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV. The computational screening resulted in the prioritization and purchase of 165 compounds for experimental characterization, which led to 11 hits that inhibit viral entry in both EBOV-GP-pseudotyped virus and EBOV transcription-and replicationcompetent virus-like particle (trVLP) systems. Molecular dynamics (MD) simulations in conjunction with genome analysis identified 7 highly conserved residues across different Ebola virus strains (E564.A, A568.A, L571.A, F572.A, T566.C, L569.C, and L573.C) that contribute a majority of the favorable interactions between the compounds and GP2. cache = ./cache/cord-003779-5yhoiv76.txt txt = ./txt/cord-003779-5yhoiv76.txt === reduce.pl bib === id = cord-017811-w38mbvdw author = Volchkov, Viktor title = Proteolytic Processing of Filovirus Glycoproteins date = 2018-02-16 pages = extension = .txt mime = text/plain words = 3525 sentences = 186 flesch = 53 summary = After entering cells by macropinocytosis, the glycan cap and the mucin-like domain are removed from GP1 by endosomal cathepsins B and L exposing the binding site for the Niemann-Pick C1 receptor. The surface glycoprotein of MARV is proteolytically processed in a similar way as that of EBOV; two precursor molecules and mature GP1,2 consisting of the disulfide-linked cleavage products GP1 and GP2 were identified in cells expressing MARV GP and in Marburg virions (Volchkov et al. Like EBOV, MARV enters cells by macropinocytosis and endosomal fusion, but there are some differences in the structure and in endosomal processing of the glycoproteins. Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression Endoproteolytic processing of the Ebola virus envelope glycoprotein: cleavage is not required for function cache = ./cache/cord-017811-w38mbvdw.txt txt = ./txt/cord-017811-w38mbvdw.txt === reduce.pl bib === id = cord-267941-nrluar4e author = Park, Eun-Mee title = Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells date = 2018-08-23 pages = extension = .txt mime = text/plain words = 2162 sentences = 127 flesch = 55 summary = In this study, we generated recombinant virus-like particles (VLPs) against family Filoviridae, genus Ebolavirus, species Zaire ebolavirus, strain Makona (EBOV) in Drosophila melanogaster Schneider 2 (S2) cells using the EBOV Makona. eVLPs were produced by sucrose gradient ultracentrifugation of S2 cells transfected with EBOV Makona genes, and production of VLPs was confirmed by immunoblot analysis. In a previous study, VP2/6 double-layered rotavirus-like particles containing Wa capsid protein were produced in S2 cells transformed with a bicistronic expression system consisting of encephalomyocarditis virus (EMCV)-derived internal ribosomal entry site (IRES) element (Lee et al., 2011) . As shown in Fig. 1A , we confirmed that Ebola viral proteins were efficiently expressed in EBOV Makona-transfected S2 cells. Collectively, our findings suggested that the eVLPs produced by the S2 cell system in this study may be useful for the development of efficient VLP-based vaccines against EBOV. cache = ./cache/cord-267941-nrluar4e.txt txt = ./txt/cord-267941-nrluar4e.txt === reduce.pl bib === id = cord-102206-mb0qcd0b author = Seymour, Elif title = Configurable Digital Virus Counter on Robust Universal DNA Chips date = 2020-10-22 pages = extension = .txt mime = text/plain words = 5898 sentences = 284 flesch = 52 summary = 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). 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. 16 SP-IRIS has been utilized for detecting viruses in complex media using antibody microarrays by imaging chips both dry (dried after sample incubation and wash steps) and in liquid using disposable microfluidic cartridges. To demonstrate the feasibility of using the homogeneous assay in combination with the passive flow cartridge and to compare its performance to the directly immobilized antibody assay, an SP-IRIS chip was printed with anti-EBOV mAb, A' probe, and a negative DNA sequence, and washed as described previously. cache = ./cache/cord-102206-mb0qcd0b.txt txt = ./txt/cord-102206-mb0qcd0b.txt === reduce.pl bib === id = cord-003859-k8wfyj9b author = Paweska, Janusz T. title = Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date = 2019-07-24 pages = extension = .txt mime = text/plain words = 6407 sentences = 308 flesch = 51 summary = title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to evaluate and compare the diagnostic performance of EBOV IgG-indirect ELISAs based on antigens produced by classical virological and recombinant protein expression methods using human serum panels from EBOV non-infected and EBOV infected humans. cache = ./cache/cord-003859-k8wfyj9b.txt txt = ./txt/cord-003859-k8wfyj9b.txt === reduce.pl bib === id = cord-346267-l08ld2cy author = Wertheim, Joel O. title = Purifying Selection Can Obscure the Ancient Age of Viral Lineages date = 2011-06-24 pages = extension = .txt mime = text/plain words = 6414 sentences = 327 flesch = 47 summary = Over longer periods of evolutionary time (i.e., along long internal branches on a phylogenetic tree), evidence of evolution at the nucleotide level could be lost, which could bias tMRCA estimates towards younger dates (i.e., underestimate the length of these branches). The results presented here demonstrate that not accounting for purifying selection may bias tMRCA estimation in RNA viruses towards more recent dates, and a degree of correction can be realized by employing more realistic codon-based substitution models, capable of partially accounting for the biasing effect of purifying selection. Using BMCMC analysis, we inferred the substitution rate and root age under a standard nucleotide substitution model (GTR + Γ 4 ) for each of our three viral data sets: MeV/RPV/PPRV nucleoprotein, EBOV glycoprotein, and AIV neuraminidase (table 1) . The nucleotide substitution model (GTR + Γ 4 ) underestimated the length of branches simulated under empirical (IFEL) selection regimes inferred from the three viral data sets ( fig. cache = ./cache/cord-346267-l08ld2cy.txt txt = ./txt/cord-346267-l08ld2cy.txt === reduce.pl bib === id = cord-284791-bgodmbru author = Whitworth, Carrie title = Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate date = 2020-08-18 pages = extension = .txt mime = text/plain words = 5152 sentences = 250 flesch = 55 summary = The persistence of phi 6 was evaluated as a surrogate for Ebola virus (EBOV) and coronaviruses on porous and nonporous hospital surfaces. Under these laboratory-simulated Western indoor hospital conditions, we assessed the suitability of phi 6 as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses. This study evaluated the persistence of phi 6 in the presence of artificial test soil (ATS) as a potential surrogate for EBOV or coronaviruses at two absolute humidity (AH) conditions on four potential fomites: nonporous stainless steel (SS) and plastic (PL) and two types of porous hospital curtain fabrics. found that the Phi 6 was shown here in the current study to be a conservative surrogate for EBOV in a laboratory-simulated Western hospital room condition of 3.0 g/m 3 AH, persisting longer than the Makona-C05 variant (AH ϭ 3.3 g/m 3 ), with decay rates of 0.06 log 10 /d and 0.79 log 10 /h, respectively (Table 1 ). cache = ./cache/cord-284791-bgodmbru.txt txt = ./txt/cord-284791-bgodmbru.txt === reduce.pl bib === id = cord-303647-c4umbcvn author = Reed, Patricia E. title = A New Approach for Monitoring Ebolavirus in Wild Great Apes date = 2014-09-18 pages = extension = .txt mime = text/plain words = 5636 sentences = 256 flesch = 46 summary = CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. In zone A, 20 gorilla fecal samples were opportunistically collected while following habituated gorillas roughly 2 and 3 years after ebolavirus infection was confirmed in ape carcasses at that site using a combination of RT-PCR, immunohistochemistry and antigen capture [5, 9] . All human EVD outbreaks that had previously occurred in our sampling zone study are thought to be the result of handling infected wild animal carcasses, including gorillas [13] . This study represents the first time that ebolavirus antibodies have been detected in wild great ape fecal samples, and carries important implications for the future management and survival of these primates. cache = ./cache/cord-303647-c4umbcvn.txt txt = ./txt/cord-303647-c4umbcvn.txt === reduce.pl bib === id = cord-288734-xinkqs6u author = Muñoz-Fontela, César title = Ebola Virus Disease in Humans: Pathophysiology and Immunity date = 2017-03-30 pages = extension = .txt mime = text/plain words = 9957 sentences = 451 flesch = 44 summary = Discovered in 1976 during the first documented outbreak of Ebola virus disease (EVD) in the town of Yambuku in northern Zaire (today Democratic Republic of the Congo), EBOV has since caused sporadic human disease outbreaks of varying magnitude in Equatorial African countries (Sanchez et al. Antigen-presenting cells are a putative initial target of EBOV infection and previous research in animal models of disease has indicated that dendritic cells (DCs) and macrophages are early and preferred targets of EBOV and support virus replication (Geisbert et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study Sequence-based human leukocyte antigen-B typing of patients infected with Ebola virus in Uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes cache = ./cache/cord-288734-xinkqs6u.txt txt = ./txt/cord-288734-xinkqs6u.txt === reduce.pl bib === id = cord-003917-bswndfvk author = Lalle, Eleonora title = Pulmonary Involvement during the Ebola Virus Disease date = 2019-08-24 pages = extension = .txt mime = text/plain words = 5545 sentences = 245 flesch = 40 summary = Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . Interestingly, evidence collected in animal studies, in the epidemiological analysis of transmission chains, and in the most recent Ebola outbreaks suggests that EBOV may be able to cause primary pulmonary infection. cache = ./cache/cord-003917-bswndfvk.txt txt = ./txt/cord-003917-bswndfvk.txt === reduce.pl bib === id = cord-355737-o0y4rn0z author = Ng, Melinda title = Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats date = 2015-12-23 pages = extension = .txt mime = text/plain words = 8935 sentences = 422 flesch = 49 summary = To assess whether the EBOV infection defect in the African straw-colored fruit bat cells occurs at the viral entry step, we exposed an expanded panel of kidney fibroblast cell lines from four African pteropodids to VSV pseudotypes bearing GP spikes (VSV-GP) from seven filoviruses, including two non-African viruses, Reston virus (RESTV) and Lloviu virus (LLOV) ( Figure 1D ). Like the infection defect in African straw-colored fruit bat cells, this receptor binding defect was selective for EBOV GP, since GPs derived from MARV and the European filovirus, LLOV (Ng et al., 2014) , bound equivalently to all four pteropodid domain Cs ( Figure 4A ). . We conclude that a species-specific defect in virus-receptor interaction, caused by a single amino acid residue change in EhNPC1 relative to other, permissive African pteropodid NPC1 orthologs, reduces EBOV infection in African straw-colored fruit bat cells. cache = ./cache/cord-355737-o0y4rn0z.txt txt = ./txt/cord-355737-o0y4rn0z.txt === reduce.pl bib === id = cord-327641-hqnem2zs author = Ji, Ying-Jie title = Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone date = 2016-11-03 pages = extension = .txt mime = text/plain words = 5871 sentences = 300 flesch = 57 summary = BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. In the 2014 outbreak, the first lab-confirmed EVD patient was reported in May, 2014 in Guinea and since then the Zaire Ebola Virus (ZEBOV) has rapidly spread across Sierra Leone and to other West Africa countries. A retrospective, observational study was conducted using data collected from all patients with confirmed EVD who were admitted to the Holding and Treatment Center of Jui Government Hospital from October 1, 2014 to March 21, 2015. In our study, the multivariate analyses showed that EBOV viral load, abdominal pain, confusion, conjunctivitis, and vomiting were independently associated with the death outcome of EVD patients. cache = ./cache/cord-327641-hqnem2zs.txt txt = ./txt/cord-327641-hqnem2zs.txt === reduce.pl bib === id = cord-001542-f089bs8r author = Lai, Kang Yiu title = Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date = 2014-11-28 pages = extension = .txt mime = text/plain words = 11274 sentences = 604 flesch = 42 summary = These may include monoclonal antibody (mAbs)-based therapies (e.g. ZMapp), anti-sense phosphorodiamidate morpholino oligomers (PMO AVI-6002), lipid nanoparticle small interfering RNA (LNP-siRNA: TKM-Ebola), and an EBOV glycoprotein-based vaccine using live-attenuated recombinant vesicular stomatitis virus (rVSV-EBOGP) or a chimpanzee adenovirus (rChAd-EBOGP)-based vector. The GP2 of the EBOV is able to counter the interferon (IFN)-inducible antiviral protein tetherin which restricts the VP40-dependent budding of the progeny viral particles from infected cells [16] [17] [18] . Currently available therapeutic agents that are effective in targeting the EBOV infection in cell or animal studies may include convalescent plasma, favipiravir, chloroquine, amiodarone, dronedarone, verapamil, clomiphene, toremifene, IFN-β, Na + /K + exchangers, Na + /K + -ATPase pump inhibitors, and antioxidants. The anti-EBOV activity of clomiphene and toremifene is dependent not on its estrogen receptor antagonistic action but upon the ability of both drugs to induce a Niemann-Pick C-like phenotype to inhibit viral entry at late endosome. cache = ./cache/cord-001542-f089bs8r.txt txt = ./txt/cord-001542-f089bs8r.txt === reduce.pl bib === id = cord-330647-w1bpeqzg author = Wong, Samson Sai-Yin title = Ebola virus disease in nonendemic countries date = 2015-05-31 pages = extension = .txt mime = text/plain words = 8637 sentences = 507 flesch = 41 summary = The largest outbreak of Ebola virus disease (EVD) in history has renewed interest in filoviruses and has provided an unprecedented impetus to the development of new therapeutics and vaccines for this highly lethal infection. Nucleic acid amplification is the diagnostic test of choice because of its high sensitivity (especially in the early phase of illness); its ability to differentiate between different agents of viral hemorrhagic fever; and its relatively lower biohazard, if the viruses are appropriately inactivated; and because antigen and antibody assays are often unavailable in laboratories in nonendemic countries. 119e123 Animal studies also demonstrate the efficacy of favipiravir in the treatment of Junín virus, arenavirus, and EBOV hemorrhagic fevers, and the drug was used to treat human EVD in the 2014 West African epidemic. cache = ./cache/cord-330647-w1bpeqzg.txt txt = ./txt/cord-330647-w1bpeqzg.txt === reduce.pl bib === id = cord-272576-ez731lif author = Wada, Yoshiko title = Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date = 2016-11-03 pages = extension = .txt mime = text/plain words = 5641 sentences = 273 flesch = 50 summary = To face the world-wide threats caused by zoonotic RNA viruses, which suddenly cause serious outbreaks by invasion from nonhuman hosts and mutate rapidly, we must understand the molecular evolutionary changes in their genome sequences extensively by innovating various technologies, including those used in big data analyses, e.g., large-scale word count. The present time-series analysis on influenza A genomes showed that the 20-mers exhibiting the most evident directional changes observed in common for three different subtypes corresponded to several influenza A siRNAs, which were experimentally validated. The present study focused on time-series changes, but not on data variations caused largely by random mutations and sequencing uncertainty, and therefore, average characteristics of strains isolated in a similar period were analyzed, summing up the sequences isolated in one month and calculating an averaged mononucleotide composition for each month (Fig. 1b) . cache = ./cache/cord-272576-ez731lif.txt txt = ./txt/cord-272576-ez731lif.txt === reduce.pl bib === id = cord-354068-4qlk6y7h author = Friedrich, Brian M. title = Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date = 2012-09-21 pages = extension = .txt mime = text/plain words = 10605 sentences = 540 flesch = 44 summary = Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge. cache = ./cache/cord-354068-4qlk6y7h.txt txt = ./txt/cord-354068-4qlk6y7h.txt === reduce.pl bib === id = cord-297082-2rhoffx2 author = Yu, Changqing title = MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date = 2020-09-15 pages = extension = .txt mime = text/plain words = 6423 sentences = 410 flesch = 61 summary = Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. As a control, serine incorporator 5 (SERINC5) protein In addition, FLAG-tagged furin was expressed with HA-tagged human MARCH8 and GPΔMLD in 293T cells. In addition, when the furin-VN/GP-VC pair was expressed with MARCH8, their colocalization was also detected (Fig. 2C ), confirming that these three molecules form a complex in live cells. MARCH8 proteins from different species strongly increased GP 1 and GP 1 ΔMLD expression in cells but completely blocked their secretions (Fig. 7C, lanes 1 to 8) . cache = ./cache/cord-297082-2rhoffx2.txt txt = ./txt/cord-297082-2rhoffx2.txt === reduce.pl bib === id = cord-336986-rmxin1da author = De Clercq, Erik title = New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections date = 2019-08-07 pages = extension = .txt mime = text/plain words = 2711 sentences = 221 flesch = 57 summary = Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. Abstract: Eight differentc ompounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/oro ther hemorrhagic fever virus (HFV) infections.T hey can be considered as either (i)adenine analogues (3-deazaneplanocin A, galidesivir,G S-6620 andr emdesivir) or (ii)guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). [26] It wasa lso found active against other emerging viruses such as respiratory syncytial virus (RSV) and hepatitis Cv irus (HCV),a nd the presence of the 1'-cyano group in remdesivir wasf ound to be critical in providing selectivity toward the viral (RNA) polymerases. cache = ./cache/cord-336986-rmxin1da.txt txt = ./txt/cord-336986-rmxin1da.txt === reduce.pl bib === id = cord-002463-qhtj1pef author = Dash, Raju title = In silico-based vaccine design against Ebola virus glycoprotein date = 2017-03-21 pages = extension = .txt mime = text/plain words = 5830 sentences = 358 flesch = 50 summary = Top scored eiptope subjected to 100 ns MD simulation **RMSF **RMSD **Hydrogen bond occupency analysis Secquence, having highest vaxijen score Prediction of B cell epitope, using-**T cell epitope prediction by proteasomal C terminal cleavage, TAP transport efficiency and MHC class 1 binding **Epitopes with IC50 value less than 50 for their binding to MHC class 1 molecule from IEDB analysis along with binding to highest number of alleles in both analyses were chosen **Epitope conservancy analysis **Population coverage analysis **Kolaskar and Tongaonkar antigenicity scale 48 **Emini surface accessibility prediction 47 **Karplus and Schulz flexibility prediction 49 **Bepipred linear epitope prediction 50 **Chou and Fasman beta turn prediction 52 Vaxijen analysis with a threshold score of >0. We also validated each epitope by molecular docking simulation and MM-GBSA/MM-PBSA studies with HLA-A*32:15 protein, as it was found common in the results from MHC-I binding interaction analysis. cache = ./cache/cord-002463-qhtj1pef.txt txt = ./txt/cord-002463-qhtj1pef.txt === reduce.pl bib === id = cord-256187-ofp7tupv author = Kühl, A. title = How Ebola Virus Counters the Interferon System date = 2012-09-07 pages = extension = .txt mime = text/plain words = 8609 sentences = 439 flesch = 49 summary = Furthermore, VP24 can shut down the host's IFN-a/b and IFN-c Recognition of viral pathogen-associated molecular patterns (PAMPs) by PRRs (purple) in infected cells initiates a signalling cascade including adaptor molecules (blue) and kinases (green), which activate transcription factors (red) that induce the expression of type I IFNs and ISGs (left panel). Additionally, VP35 blocks multiple steps of the innate antiviral defence (Fig. 4) , such as the signalling pathways leading to the expression of type I IFNs and type I IFN-induced genes, double-stranded (ds) RNA-dependent protein kinase (PKR) translation inhibition and RNA silencing Cárdenas et al., 2006; Feng et al., 2007; Haasnoot et al., 2007) . The tetherin protein (HM1.24, BST-2, CD317) was identified as a type I interferon-inducible host cellular factor, which restricts release of progeny HIV-1 particles from infected cells (Neil et al., 2008; Van Damme et al., 2008) . cache = ./cache/cord-256187-ofp7tupv.txt txt = ./txt/cord-256187-ofp7tupv.txt === reduce.pl bib === id = cord-337998-08tknscm author = Sztuba-Solinska, Joanna title = A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8 date = 2016-11-16 pages = extension = .txt mime = text/plain words = 8269 sentences = 434 flesch = 51 summary = Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. 3E-5E-GFP minigenome RNA secondary structure and host protein interactions were examined using selective 2 -hydroxyl acylation analyzed by primer extension (SHAPE) (38, 39) , antisense-interfered SHAPE (aiSHAPE) (40) , electrophoretic mobility shift assays (EMSA), siRNA, and mutational analysis, using both the 3E-5E-GFP minigenome system and EBOV reverse genetics. The secondary structure of the EBOV 3E-5E-GFP minigenome RNA predicted by RNAstructure software version 5.7 (48) and chemical probing data from SHAPE were used to generate 10 three-dimensional (3D) models for the trailer-to-leader panhandle interaction in the wt-EBOV genome and variants, A30U and A26U/A30U, using open-source RNAComposer, version 1.0 (http://rnacomposer.cs.put.poznan.pl/). cache = ./cache/cord-337998-08tknscm.txt txt = ./txt/cord-337998-08tknscm.txt === reduce.pl bib === id = cord-322748-a5131tv9 author = Yates, Mary K. title = Flex-nucleoside analogues – Novel therapeutics against filoviruses date = 2017-06-15 pages = extension = .txt mime = text/plain words = 1492 sentences = 78 flesch = 53 summary = Most recently GS-5734, a monophosphoramidate prodrug adenosine analogue which targets EBOV RNA-dependent RNA polymerase (RdRp), exhibited very potent activity against both EBOV and MARV, 17, 18 further demonstrating the potential for finding effective nucleoside inhibitors of filoviruses. After the successful synthesis of the three Flex-analogues 1, 2, and 3, the compounds were screened against a panel of filoviruses including EBOV, MARV, and SUDV, as well as other hemorrhagic fever viruses such as Lassa and Rift Valley Fever. The second series of assays utilized Huh7 cells infected with recombinant reporter EBOV, Lassa, and Rift Valley Fever viruses. Within this study we found that both compounds 1 and 3 exhibited antiviral activity against a recombinant reporter EBOV in Huh7 cells, though surprisingly the McGuigan prodrug was 10-fold less potent (EC 50 = 2.2 ± 0.3 lM and 27.2 ± 2.2 lM respectively). cache = ./cache/cord-322748-a5131tv9.txt txt = ./txt/cord-322748-a5131tv9.txt === reduce.pl bib === id = cord-334560-1j9zmuub author = Hunt, Catherine L. title = Filovirus Entry: A Novelty in the Viral Fusion World date = 2012-02-07 pages = extension = .txt mime = text/plain words = 6445 sentences = 301 flesch = 48 summary = Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. However, for reasons that are not entirely clear, this type of study has not been successful in identifying cell surface proteins that directly interact with EBOV GP to mediate virus entry [41, 42] . However, as both of these regions can be deleted from EBOV GP 1 without loss of viral transduction efficiency [16, [50] [51] [52] , it is likely that C-type lectins increase filovirus attachment to cells rather than serving as cellular receptors that mediate internalization of the virus into endosomes [53] . cache = ./cache/cord-334560-1j9zmuub.txt txt = ./txt/cord-334560-1j9zmuub.txt === reduce.pl bib === id = cord-294342-7ycgd0h7 author = Markosyan, Ruben M. title = Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date = 2016-01-05 pages = extension = .txt mime = text/plain words = 11740 sentences = 548 flesch = 56 summary = On the question of low pH, we found that activation of cathepsins by acidity is the sole cause for augmentation of fusion: if EBOV GP on the cell surface is artificially cleaved by thermolysin in the presence of cathepsin inhibitors, the extent of fusion is independent of pH. We used thermolysin-treated effector cells to maximize cleavage of EBOV GP and found that adding CPZ either 30, 45, or 60 min after reneutralization did not induce any dye spread above that already observed, strongly indicating that a negligible percentage of cells were hemifused, but not fused, at any given time. The extent of fusion was greater when the inhibitor was not added (control): this indicates that delivery to the cell surface of EBOV GP cleaved by endosomal cathepsin (subsequent to thermolysin treatment) significantly contributes to fusion. cache = ./cache/cord-294342-7ycgd0h7.txt txt = ./txt/cord-294342-7ycgd0h7.txt === reduce.pl bib === id = cord-296399-vvbjulm9 author = Brinkmann, Constantin title = The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date = 2017-12-07 pages = extension = .txt mime = text/plain words = 7009 sentences = 340 flesch = 44 summary = Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. At 1 h post infection, the inoculum was removed and the cells were transfected with expression plasmids for VSV-N, -P and -L (see above) as well as the respective, plasmid-encoded VSV Ã anti-genome (the genome is preceded by a T7 promotor sequence and followed by a hepatitis delta virus ribozyme and a T7 terminator sequence for cytoplasmic production of negative-sensed viral genomes that are template for transcription and genome replication) using Lipofectamine2000 (ThermoFisher Scientific, Dreiech) as transfection reagent. In order to analyze tetherin antagonism by VSV proteins, we employed a previously reported virus-like particle (VLP) release assay, which measures release of HIV-Gag-based VLPs from transfected 293T cells and its blockade by tetherin [27, 32] . cache = ./cache/cord-296399-vvbjulm9.txt txt = ./txt/cord-296399-vvbjulm9.txt === reduce.pl bib === id = cord-325423-d212h4bp author = Carrion, Ricardo title = A small nonhuman primate model for filovirus-induced disease date = 2011-11-01 pages = extension = .txt mime = text/plain words = 4925 sentences = 274 flesch = 42 summary = To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. Nonhuman primates (NHPs) are the preferred animal model for human filovirus infection because infection with EBOZ and MARV isolated from humans results in fatal hemorrhagic disease. In animals inoculated with the 10 PFU and surviving to 5 dpi, hepatic disease was more severe and characterized by multifocal to coalescing hepatocellular coagulative necrosis infiltrated by small to moderate numbers of neutrophils. Consistent with the macaque model, experimental inoculation of marmosets with MARV also results in delayed onset of disease, with death occurring 3 to 4 days later than that seen with marmosets infected with EBOV. Further evidence that the marmoset mimics human disease is that microscopic examination of tissue from EBOV-infected animals reveals widespread fibrin deposition that is a hallmark of coagulation abnormalities (Geisbert et al., 2003c,d; Jaax et al., 1996) . cache = ./cache/cord-325423-d212h4bp.txt txt = ./txt/cord-325423-d212h4bp.txt === reduce.pl bib === id = cord-342052-v4y1xc90 author = Horigan, Verity title = Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States date = 2017-10-02 pages = extension = .txt mime = text/plain words = 12804 sentences = 611 flesch = 55 summary = The use of the same framework and generic data sources for all EU Member States (MS) allows for a relative comparison of the probability of virus introduction and of the importance of the routes of introduction among MSs. According to the model wEBOV posed the highest risk of an introduction event within the EU, followed by MARV and MERS-CoV. Since 2003 there have been a number of large-scale human outbreaks of bat-borne diseases e.g. Zaire ebolavirus (EBOV) and Severe Acute Respiratory Syndrome (SARS) in Western Africa and Asia respectively, whilst a significant number of human cases of Nipah virus (NiV) are reported in Bangladesh every year (IEDCR, 2014) . To address this need, a generic quantitative risk assessment framework for the entry of bat-borne zoonotic viruses to the EU was developed (Simons et al., 2016) , considering the pathways: human travel, live animal movement, legal trade of food products and illegal trade of bushmeat. cache = ./cache/cord-342052-v4y1xc90.txt txt = ./txt/cord-342052-v4y1xc90.txt === reduce.pl bib === id = cord-350083-kldu8q8x author = Oany, Arafat Rahman title = Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach date = 2015-08-08 pages = extension = .txt mime = text/plain words = 5019 sentences = 315 flesch = 51 summary = title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. To date, information regarding the processing, structure and functions of Ebola virus (EBOV) protein L (EBOL) demonstrates that it is an RNA-dependent RNA polymerase, with the assistance of VP35. In the present study, we have followed immunoinformatics approaches for designing potential conserved epitope candidate for the utility of vaccine development against the deadly Ebola virus, with an expectation of further wet lab validation. Protein variability server predicted the variability of the conserved region of the RNA-dependent RNA polymerase-L ( Fig. 10) to ensure that the proposed epitope is within the invariable region. Design of an epitope-based peptide vaccine against spike protein of human corona virus: an in silico approach cache = ./cache/cord-350083-kldu8q8x.txt txt = ./txt/cord-350083-kldu8q8x.txt === reduce.pl bib === id = cord-350565-mejd7blb author = Lewnard, Joseph A title = Emerging Challenges and Opportunities in Infectious Disease Epidemiology date = 2019-03-16 pages = extension = .txt mime = text/plain words = 6614 sentences = 289 flesch = 29 summary = We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. Although serosurveys have bolstered recent efforts to understand the geographic range and clinical spectrum of EBOV and Zika virus infections (47, 48) , the enhancement of dengue hemorrhagic fever risk by prior exposure (49) , and the role of immunologic history in influenza susceptibility and vaccine response (50) , there remain few examples of public health programs undertaking serological studies for routine surveillance, at least in civilian populations (51) . cache = ./cache/cord-350565-mejd7blb.txt txt = ./txt/cord-350565-mejd7blb.txt === reduce.pl bib === id = cord-335093-tc1qo2k0 author = Gehring, Gerrit title = The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry date = 2014-08-01 pages = extension = .txt mime = text/plain words = 5187 sentences = 267 flesch = 48 summary = Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. While most drugs had no major effect on filovirus GP-mediated cell entry, amiodarone was found to reduce the detectable signal by over 99%, and thus more strongly than FYdmk, which achieved 86% -98% inhibition. Filoviral GP-mediated entry into primary human umbilical vein endothelial cells and in macrophages derived from primary human monocytes was significantly inhibited at amiodarone concentrations below 1 mg/mL for both MARV and EBOV GP while amiodarone had no effect on the transduction of primary hepatocytes ( Figure S3 , available as Supplementary data at JAC Online). cache = ./cache/cord-335093-tc1qo2k0.txt txt = ./txt/cord-335093-tc1qo2k0.txt === reduce.pl bib === id = cord-305653-f9vqn96o author = Schmidt, Rebecca title = Generation of therapeutic antisera for emerging viral infections date = 2018-10-05 pages = extension = .txt mime = text/plain words = 7902 sentences = 377 flesch = 46 summary = Animal-origin purified IgG 27 and IgG fragment preparations are still routinely used as antivenoms, and even though immunization of horses with inactivated EBOV failed to yield effective therapeutic antisera, 28 equine hyperimmune sera produced using EBOV virus-like particles (VLPs) conferred protection against lethal challenge in rodents. To determine the importance of this aspect for the induction of functional antibodies, we compared adjuvanted EBOV VLPs with vector vaccines based on the replication-deficient modified vaccinia Ankara virus (MVA) that expresses either the GP protein of the Zaire EBOV Guéckédou strain alone or in combination with VP40 (unpublished data), and the replication-competent VSVΔG/EBOV-GP. Even though the neutralizing antibodies were again only detected after the first boost in the group immunized with adjuvanted EBOV VLPs, titers ultimately reached levels around 100 (Fig. 2b) , illustrating that de novo protein expression is not required for efficient induction of functional antibodies. cache = ./cache/cord-305653-f9vqn96o.txt txt = ./txt/cord-305653-f9vqn96o.txt === reduce.pl bib === id = cord-352492-6ihyiwgb author = Eickmann, Markus title = Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively date = 2018-05-06 pages = extension = .txt mime = text/plain words = 3005 sentences = 164 flesch = 55 summary = title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively STUDY DESIGN AND METHODS: PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity. The results of the infectivity assay demonstrated that UVC irradiation dose-dependently inactivated EBOV and MERS-CoV in plasma-reduced PCs (Table 1 ). Although EBOV is highly infectious and low doses of less than 10 plaque-forming units of the virus are sufficient to cause disease, 32 the ability of the UVC-and MB/ light-based systems to reduce MERS-CoV and EBOV infectivity in blood products by several log steps may be sufficient to eliminate or significantly reduce the risk of transmission via the transfusion of PCs or plasma. cache = ./cache/cord-352492-6ihyiwgb.txt txt = ./txt/cord-352492-6ihyiwgb.txt ===== Reducing email addresses cord-272576-ez731lif Creating transaction Updating adr table ===== Reducing keywords cord-002013-rb9xdzro cord-002676-zwkl1ywk cord-001764-njzyu4mv cord-102763-tc1z0nm9 cord-001546-ndz3oarf cord-274377-57zy6unz cord-011129-btaxvmsr cord-296517-414grqif cord-284845-on97zu6w cord-300133-yc2wxgid cord-000547-adfigzc1 cord-001513-p7v5p036 cord-004335-bw3tziup cord-002935-jq1xumrh cord-000804-0hlj6r10 cord-288029-6l91knu3 cord-002185-oz7hras7 cord-293481-bmfj50fb cord-002500-9p2n8tjx cord-344316-mwnnmwnw cord-279152-yh7x7w2q cord-276437-5gkdotvt cord-289413-mbrw85og cord-004126-u6ts87ur cord-004069-nuep8nim cord-318587-ewvnkdr2 cord-003779-5yhoiv76 cord-017811-w38mbvdw cord-267941-nrluar4e cord-102206-mb0qcd0b cord-003859-k8wfyj9b cord-346267-l08ld2cy cord-284791-bgodmbru cord-303647-c4umbcvn cord-288734-xinkqs6u cord-003917-bswndfvk cord-355737-o0y4rn0z cord-327641-hqnem2zs cord-001542-f089bs8r cord-330647-w1bpeqzg cord-272576-ez731lif cord-354068-4qlk6y7h cord-297082-2rhoffx2 cord-336986-rmxin1da cord-002463-qhtj1pef cord-256187-ofp7tupv cord-337998-08tknscm cord-322748-a5131tv9 cord-334560-1j9zmuub cord-294342-7ycgd0h7 cord-296399-vvbjulm9 cord-325423-d212h4bp cord-342052-v4y1xc90 cord-350083-kldu8q8x cord-350565-mejd7blb cord-352492-6ihyiwgb cord-335093-tc1qo2k0 cord-305653-f9vqn96o Creating transaction Updating wrd table ===== Reducing urls cord-001764-njzyu4mv cord-011129-btaxvmsr cord-274377-57zy6unz cord-284845-on97zu6w cord-001513-p7v5p036 cord-002935-jq1xumrh cord-276437-5gkdotvt cord-289413-mbrw85og cord-004126-u6ts87ur cord-004069-nuep8nim cord-318587-ewvnkdr2 cord-003779-5yhoiv76 cord-346267-l08ld2cy cord-284791-bgodmbru cord-003917-bswndfvk cord-355737-o0y4rn0z cord-272576-ez731lif cord-002463-qhtj1pef cord-337998-08tknscm cord-322748-a5131tv9 cord-296399-vvbjulm9 cord-305653-f9vqn96o Creating transaction Updating url table ===== Reducing named entities cord-001764-njzyu4mv cord-102763-tc1z0nm9 cord-002013-rb9xdzro cord-002676-zwkl1ywk cord-001546-ndz3oarf cord-274377-57zy6unz cord-296517-414grqif cord-011129-btaxvmsr cord-284845-on97zu6w cord-300133-yc2wxgid cord-000547-adfigzc1 cord-001513-p7v5p036 cord-004335-bw3tziup cord-002935-jq1xumrh cord-000804-0hlj6r10 cord-288029-6l91knu3 cord-002185-oz7hras7 cord-293481-bmfj50fb cord-002500-9p2n8tjx cord-344316-mwnnmwnw cord-279152-yh7x7w2q cord-276437-5gkdotvt cord-289413-mbrw85og cord-004126-u6ts87ur cord-004069-nuep8nim cord-318587-ewvnkdr2 cord-003779-5yhoiv76 cord-017811-w38mbvdw cord-267941-nrluar4e cord-102206-mb0qcd0b cord-003859-k8wfyj9b cord-284791-bgodmbru cord-346267-l08ld2cy cord-288734-xinkqs6u cord-303647-c4umbcvn cord-003917-bswndfvk cord-355737-o0y4rn0z cord-327641-hqnem2zs cord-272576-ez731lif cord-001542-f089bs8r cord-330647-w1bpeqzg cord-354068-4qlk6y7h cord-297082-2rhoffx2 cord-336986-rmxin1da cord-002463-qhtj1pef cord-256187-ofp7tupv cord-337998-08tknscm cord-322748-a5131tv9 cord-334560-1j9zmuub cord-294342-7ycgd0h7 cord-296399-vvbjulm9 cord-325423-d212h4bp cord-350083-kldu8q8x cord-350565-mejd7blb cord-352492-6ihyiwgb cord-342052-v4y1xc90 cord-335093-tc1qo2k0 cord-305653-f9vqn96o Creating transaction Updating ent table ===== Reducing parts of speech cord-102763-tc1z0nm9 cord-002013-rb9xdzro cord-002676-zwkl1ywk cord-001764-njzyu4mv cord-001546-ndz3oarf cord-274377-57zy6unz cord-296517-414grqif cord-011129-btaxvmsr cord-300133-yc2wxgid cord-284845-on97zu6w cord-000547-adfigzc1 cord-001513-p7v5p036 cord-004335-bw3tziup cord-002935-jq1xumrh cord-288029-6l91knu3 cord-002185-oz7hras7 cord-293481-bmfj50fb cord-000804-0hlj6r10 cord-002500-9p2n8tjx cord-344316-mwnnmwnw cord-279152-yh7x7w2q cord-276437-5gkdotvt cord-289413-mbrw85og cord-004126-u6ts87ur cord-004069-nuep8nim cord-318587-ewvnkdr2 cord-003779-5yhoiv76 cord-017811-w38mbvdw cord-267941-nrluar4e cord-102206-mb0qcd0b cord-003859-k8wfyj9b cord-346267-l08ld2cy cord-284791-bgodmbru cord-303647-c4umbcvn cord-288734-xinkqs6u cord-003917-bswndfvk cord-355737-o0y4rn0z cord-327641-hqnem2zs cord-272576-ez731lif cord-001542-f089bs8r cord-330647-w1bpeqzg cord-297082-2rhoffx2 cord-354068-4qlk6y7h cord-336986-rmxin1da cord-002463-qhtj1pef cord-256187-ofp7tupv cord-337998-08tknscm cord-322748-a5131tv9 cord-325423-d212h4bp cord-350083-kldu8q8x cord-296399-vvbjulm9 cord-352492-6ihyiwgb cord-334560-1j9zmuub cord-350565-mejd7blb cord-335093-tc1qo2k0 cord-305653-f9vqn96o cord-294342-7ycgd0h7 cord-342052-v4y1xc90 Creating transaction Updating pos table Building ./etc/reader.txt cord-000804-0hlj6r10 cord-001542-f089bs8r cord-342052-v4y1xc90 cord-001542-f089bs8r cord-288734-xinkqs6u cord-011129-btaxvmsr number of items: 58 sum of words: 367,749 average size in words: 6,340 average readability score: 49 nouns: virus; cells; infection; cell; protein; viruses; disease; entry; patients; fusion; antibody; vaccine; data; outbreak; host; study; treatment; proteins; activity; fever; antibodies; analysis; glycoprotein; replication; expression; filovirus; studies; gp; model; receptor; time; type; response; assay; mice; infections; responses; membrane; surface; transmission; results; protection; days; domain; vaccines; role; samples; levels; plasma; particles verbs: used; showed; based; binding; infected; including; mediated; express; induce; inhibited; suggest; contain; provides; observed; identified; indicating; required; increased; associated; reported; following; demonstrated; found; described; detecting; tested; resulted; compared; determine; cause; reduced; neutralizing; occurs; performed; treated; emerged; targeting; generated; confirmed; known; produced; obtain; protected; given; developed; blocked; collected; leading; measured; considered adjectives: viral; human; clinical; high; different; specific; immune; anti; antiviral; hemorrhagic; cellular; single; similar; like; respiratory; dependent; non; available; recombinant; several; infectious; potential; important; severe; molecular; small; multiple; negative; lethal; low; higher; positive; therapeutic; infected; african; early; first; recent; new; acute; dendritic; novel; essential; significant; common; effective; structural; protective; large; many adverbs: also; however; well; previously; therefore; highly; respectively; recently; significantly; even; first; directly; currently; prior; still; furthermore; approximately; moreover; often; especially; subsequently; finally; together; yet; indeed; likely; additionally; relatively; rapidly; later; experimentally; less; fully; generally; specifically; interestingly; much; completely; potentially; now; next; long; least; effectively; primarily; possibly; mainly; rather; alone; largely pronouns: we; it; their; its; i; our; they; them; he; us; his; you; your; itself; rad5; themselves; one; her; evlps; sgp; trim30; tmrcas; pdcs; ours; myosin-10; my; mrnas; me; imagej; igg1; i450; i)adenine; him; a129 proper nouns: EBOV; Ebola; GP; RNA; VSV; Fig; EVD; MARV; Marburg; VP35; NPC1; IFN; HIV-1; NP; Africa; C; MERS; VP40; ebola; CoV; SARS; Zaire; G; T; Virus; remdesivir; ELISA; PCR; Vero; VP24; endosomal; VLP; Congo; pH; tetherin; Table; Ebolavirus; West; PBS; GP2; Sierra; Leone; E6; mg; Niemann; Republic; RT; VP30; USA; M keywords: ebov; ebola; virus; rna; evd; mers; sars; npc1; marv; ifn; cell; vsv; vp35; vaccine; infection; vp40; vlp; mhc; marburg; hiv-1; elisa; vsvΔg; vpu; vero; united; tnc; theraflex; tetherin; tcid; supplementary; study; siglec-1; sample; response; respiratory; republic; remdesivir; pfu; pbs; patient; outbreak; mva; mpxv; moi; march8; iris; ifnar; i49; hspa8; hspa5 one topic; one dimension: virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828711/ titles(s): Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection three topics; one dimension: virus; virus; virus file(s): https://doi.org/10.1371/journal.ppat.1005373, https://api.elsevier.com/content/article/pii/S2352352217301408, https://doi.org/10.1128/cmr.00162-20 titles(s): Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger | Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States | Remdesivir against COVID-19 and Other Viral Diseases five topics; three dimensions: virus ebov ebola; virus ebola ebov; gp virus ebov; virus ebov ebola; ebov fusion virus file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334593/, https://api.elsevier.com/content/article/pii/S2352352217301408, https://www.ncbi.nlm.nih.gov/pubmed/22470835/, https://doi.org/10.1038/s41541-018-0082-4, https://www.ncbi.nlm.nih.gov/pubmed/32591388/ titles(s): Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus | Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States | Filovirus Entry: A Novelty in the Viral Fusion World | Generation of therapeutic antisera for emerging viral infections | Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate Type: cord title: keyword-ebov-cord date: 2021-05-24 time: 23:39 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:ebov ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-001546-ndz3oarf author: Ayithan, Natarajan title: Virus-Like Particles Activate Type I Interferon Pathways to Facilitate Post-Exposure Protection against Ebola Virus Infection date: 2015-02-26 words: 5128 sentences: 298 pages: flesch: 52 cache: ./cache/cord-001546-ndz3oarf.txt txt: ./txt/cord-001546-ndz3oarf.txt summary: Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. The aim of this study was to further investigate molecular bases of postexposure protection by VLPs. Based on our previous report that VLPs stimulate type I IFN expression in DCs and macrophages, in vitro, we focused on the role of type I IFN signaling, and found that post-exposure VLP treatment leads to accelerated activation of IFN signaling, resulting in early induction of ISGs. Significantly, VLP stimulated ISG induction coincided with the attenuation of proinflammatory cytokine surge in EBOV infected mice. abstract: Ebola virus (EBOV) causes a severe hemorrhagic disease with high fatality. Virus-like particles (VLPs) are a promising vaccine candidate against EBOV. We recently showed that VLPs protect mice from lethal EBOV infection when given before or after viral infection. To elucidate pathways through which VLPs confer post-exposure protection, we investigated the role of type I interferon (IFN) signaling. We found that VLPs lead to accelerated induction of IFN stimulated genes (ISGs) in liver and spleen of wild type mice, but not in Ifnar(-/-) mice. Accordingly, EBOV infected Ifnar(-/-) mice, unlike wild type mice succumbed to death even after VLP treatment. The ISGs induced in wild type mice included anti-viral proteins and negative feedback factors known to restrict viral replication and excessive inflammatory responses. Importantly, proinflammatory cytokine/chemokine expression was much higher in WT mice without VLPs than mice treated with VLPs. In EBOV infected Ifnar(-/-) mice, however, uninhibited viral replication and elevated proinflammatory factor expression ensued, irrespective of VLP treatment, supporting the view that type I IFN signaling helps to limit viral replication and attenuate inflammatory responses. Further analyses showed that VLP protection requires the transcription factor, IRF8 known to amplify type I IFN signaling in dendritic cells and macrophages, the probable sites of initial EBOV infection. Together, this study indicates that VLPs afford post-exposure protection by promoting expeditious initiation of type I IFN signaling in the host. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4342244/ doi: 10.1371/journal.pone.0118345 id: cord-000547-adfigzc1 author: Beniac, Daniel R. title: The Organisation of Ebola Virus Reveals a Capacity for Extensive, Modular Polyploidy date: 2012-01-11 words: 7782 sentences: 392 pages: flesch: 51 cache: ./cache/cord-000547-adfigzc1.txt txt: ./txt/cord-000547-adfigzc1.txt summary: METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. From the same image data set, we combined extracted volumes from tomograms with 2-D single particle processing to determine the structure of the GP spikes ( Figure 5 ) to a resolution of 14 Å as measured by the Fourier Shell Correlation (FSC) 0.5 criterion. Analysis of 2090 distinct intact virions with a nucleocapsid from cryo-electron micrographs shows that the most common class length (53%) of virus particles is 982679 nm ( Figure 1A , Table S1 ). abstract: BACKGROUND: Filoviruses, including Ebola virus, are unusual in being filamentous animal viruses. Structural data on the arrangement, stoichiometry and organisation of the component molecules of filoviruses has until now been lacking, partially due to the need to work under level 4 biological containment. The present study provides unique insights into the structure of this deadly pathogen. METHODOLOGY AND PRINCIPAL FINDINGS: We have investigated the structure of Ebola virus using a combination of cryo-electron microscopy, cryo-electron tomography, sub-tomogram averaging, and single particle image processing. Here we report the three-dimensional structure and architecture of Ebola virus and establish that multiple copies of the RNA genome can be packaged to produce polyploid virus particles, through an extreme degree of length polymorphism. We show that the helical Ebola virus inner nucleocapsid containing RNA and nucleoprotein is stabilized by an outer layer of VP24-VP35 bridges. Elucidation of the structure of the membrane-associated glycoprotein in its native state indicates that the putative receptor-binding site is occluded within the molecule, while a major neutralizing epitope is exposed on its surface proximal to the viral envelope. The matrix protein VP40 forms a regular lattice within the envelope, although its contacts with the nucleocapsid are irregular. CONCLUSIONS: The results of this study demonstrate a modular organization in Ebola virus that accommodates a well-ordered, symmetrical nucleocapsid within a flexible, tubular membrane envelope. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256159/ doi: 10.1371/journal.pone.0029608 id: cord-000804-0hlj6r10 author: Brauburger, Kristina title: Forty-Five Years of Marburg Virus Research date: 2012-10-01 words: 14922 sentences: 730 pages: flesch: 45 cache: ./cache/cord-000804-0hlj6r10.txt txt: ./txt/cord-000804-0hlj6r10.txt summary: While the ectodomain, which is mainly formed by GP 1 , mediates binding to entry factors and receptors [87] [88] [89] [90] [91] [92] [93] [94] [95] , the transmembrane subunit GP 2 contains the fusion peptide and is presumed to mediate fusion of the viral and the cellular membrane based on similarity to EBOV GP 2 both at the amino acid and structural level [96, 97] . The IFN-inducible antiviral protein tetherin was shown to block the release of VP40-induced virus-like MARV and EBOV particles, suggesting that tetherin might act as a restriction factor for filovirus release [102, 103] . After the nucleocapsid is released into the cytoplasm of the infected cell, transcription and replication of the viral RNA genome takes place (Figure 7 ). Virus-like particles exhibit potential as a pan-filovirus vaccine for both Ebola and Marburg viral infections abstract: In 1967, the first reported filovirus hemorrhagic fever outbreak took place in Germany and the former Yugoslavia. The causative agent that was identified during this outbreak, Marburg virus, is one of the most deadly human pathogens. This article provides a comprehensive overview of our current knowledge about Marburg virus disease ranging from ecology to pathogenesis and molecular biology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3497034/ doi: 10.3390/v4101878 id: cord-296399-vvbjulm9 author: Brinkmann, Constantin title: The glycoprotein of vesicular stomatitis virus promotes release of virus-like particles from tetherin-positive cells date: 2017-12-07 words: 7009 sentences: 340 pages: flesch: 44 cache: ./cache/cord-296399-vvbjulm9.txt txt: ./txt/cord-296399-vvbjulm9.txt summary: Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. At 1 h post infection, the inoculum was removed and the cells were transfected with expression plasmids for VSV-N, -P and -L (see above) as well as the respective, plasmid-encoded VSV Ã anti-genome (the genome is preceded by a T7 promotor sequence and followed by a hepatitis delta virus ribozyme and a T7 terminator sequence for cytoplasmic production of negative-sensed viral genomes that are template for transcription and genome replication) using Lipofectamine2000 (ThermoFisher Scientific, Dreiech) as transfection reagent. In order to analyze tetherin antagonism by VSV proteins, we employed a previously reported virus-like particle (VLP) release assay, which measures release of HIV-Gag-based VLPs from transfected 293T cells and its blockade by tetherin [27, 32] . abstract: Vesicular stomatitis virus (VSV) release from infected cells is inhibited by the interferon (IFN)-inducible antiviral host cell factor tetherin (BST-2, CD317). However, several viruses encode tetherin antagonists and it is at present unknown whether residual VSV spread in tetherin-positive cells is also promoted by a virus-encoded tetherin antagonist. Here, we show that the viral glycoprotein (VSV-G) antagonizes tetherin in transfected cells, although with reduced efficiency as compared to the HIV-1 Vpu protein. Tetherin antagonism did not involve alteration of tetherin expression and was partially dependent on a GXXXG motif in the transmembrane domain of VSV-G. However, mutation of the GXXXG motif did not modulate tetherin sensitivity of infectious VSV. These results identify VSV-G as a tetherin antagonist in transfected cells but fail to provide evidence for a contribution of tetherin antagonism to viral spread. url: https://www.ncbi.nlm.nih.gov/pubmed/29216247/ doi: 10.1371/journal.pone.0189073 id: cord-325423-d212h4bp author: Carrion, Ricardo title: A small nonhuman primate model for filovirus-induced disease date: 2011-11-01 words: 4925 sentences: 274 pages: flesch: 42 cache: ./cache/cord-325423-d212h4bp.txt txt: ./txt/cord-325423-d212h4bp.txt summary: To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. Nonhuman primates (NHPs) are the preferred animal model for human filovirus infection because infection with EBOZ and MARV isolated from humans results in fatal hemorrhagic disease. In animals inoculated with the 10 PFU and surviving to 5 dpi, hepatic disease was more severe and characterized by multifocal to coalescing hepatocellular coagulative necrosis infiltrated by small to moderate numbers of neutrophils. Consistent with the macaque model, experimental inoculation of marmosets with MARV also results in delayed onset of disease, with death occurring 3 to 4 days later than that seen with marmosets infected with EBOV. Further evidence that the marmoset mimics human disease is that microscopic examination of tissue from EBOV-infected animals reveals widespread fibrin deposition that is a hallmark of coagulation abnormalities (Geisbert et al., 2003c,d; Jaax et al., 1996) . abstract: Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever. url: https://www.sciencedirect.com/science/article/pii/S0042682211003965 doi: 10.1016/j.virol.2011.08.022 id: cord-002463-qhtj1pef author: Dash, Raju title: In silico-based vaccine design against Ebola virus glycoprotein date: 2017-03-21 words: 5830 sentences: 358 pages: flesch: 50 cache: ./cache/cord-002463-qhtj1pef.txt txt: ./txt/cord-002463-qhtj1pef.txt summary: Top scored eiptope subjected to 100 ns MD simulation **RMSF **RMSD **Hydrogen bond occupency analysis Secquence, having highest vaxijen score Prediction of B cell epitope, using-**T cell epitope prediction by proteasomal C terminal cleavage, TAP transport efficiency and MHC class 1 binding **Epitopes with IC50 value less than 50 for their binding to MHC class 1 molecule from IEDB analysis along with binding to highest number of alleles in both analyses were chosen **Epitope conservancy analysis **Population coverage analysis **Kolaskar and Tongaonkar antigenicity scale 48 **Emini surface accessibility prediction 47 **Karplus and Schulz flexibility prediction 49 **Bepipred linear epitope prediction 50 **Chou and Fasman beta turn prediction 52 Vaxijen analysis with a threshold score of >0. We also validated each epitope by molecular docking simulation and MM-GBSA/MM-PBSA studies with HLA-A*32:15 protein, as it was found common in the results from MHC-I binding interaction analysis. abstract: Ebola virus (EBOV) is one of the lethal viruses, causing more than 24 epidemic outbreaks to date. Despite having available molecular knowledge of this virus, no definite vaccine or other remedial agents have been developed yet for the management and avoidance of EBOV infections in humans. Disclosing this, the present study described an epitope-based peptide vaccine against EBOV, using a combination of B-cell and T-cell epitope predictions, followed by molecular docking and molecular dynamics simulation approach. Here, protein sequences of all glycoproteins of EBOV were collected and examined via in silico methods to determine the most immunogenic protein. From the identified antigenic protein, the peptide region ranging from 186 to 220 and the sequence HKEGAFFLY from the positions of 154–162 were considered the most potential B-cell and T-cell epitopes, correspondingly. Moreover, this peptide (HKEGAFFLY) interacted with HLA-A*32:15 with the highest binding energy and stability, and also a good conservancy of 83.85% with maximum population coverage. The results imply that the designed epitopes could manifest vigorous enduring defensive immunity against EBOV. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5367765/ doi: 10.2147/aabc.s115859 id: cord-336986-rmxin1da author: De Clercq, Erik title: New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections date: 2019-08-07 words: 2711 sentences: 221 pages: flesch: 57 cache: ./cache/cord-336986-rmxin1da.txt txt: ./txt/cord-336986-rmxin1da.txt summary: Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. Abstract: Eight differentc ompounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/oro ther hemorrhagic fever virus (HFV) infections.T hey can be considered as either (i)adenine analogues (3-deazaneplanocin A, galidesivir,G S-6620 andr emdesivir) or (ii)guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). [26] It wasa lso found active against other emerging viruses such as respiratory syncytial virus (RSV) and hepatitis Cv irus (HCV),a nd the presence of the 1''-cyano group in remdesivir wasf ound to be critical in providing selectivity toward the viral (RNA) polymerases. abstract: Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3‐deazaneplanocin A, galidesivir, GS‐6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS‐6620, remdesivir and pyrazofurin) are C‐nucleosides, and two of them (GS‐6620, remdesivir) also contain a phosphoramidate part. The C‐nucleoside and phosphoramidate (and for the adenine analogues the 1′‐cyano group as well) may be considered as essential attributes for their antiviral activity. url: https://doi.org/10.1002/asia.201900841 doi: 10.1002/asia.201900841 id: cord-004069-nuep8nim author: DeWald, Lisa Evans title: In Vivo Activity of Amodiaquine against Ebola Virus Infection date: 2019-12-27 words: 5707 sentences: 288 pages: flesch: 53 cache: ./cache/cord-004069-nuep8nim.txt txt: ./txt/cord-004069-nuep8nim.txt summary: A pharmacokinetic (PK) study in rhesus macaques (2 groups of 2 males and 2 females) was performed to monitor plasma concentrations of AQ (Fig. 1a ) and the active metabolite DEAQ (Fig. 1b) . samples from infected animals collected on days 0, 3, 5, and 7 postexposure and on day of necropsy (days 6, 7 or 8) were analyzed for determination of plasma levels of AQ and its metabolite DEAQ. Animals that were treated on days 0, 1 and 2 (Group 2, Fig. 7a ), had plasma DEAQ levels ranging from 0 to 205 ng/ml on days 3, 5, 7 and 8 postexposure. www.nature.com/scientificreports www.nature.com/scientificreports/ The goal of the study was to treat animals with AQ using a similar dosing strategy as for human patients, with a target blood concentration range of the parent compound AQ of 29.2 ± 10.9 ng/mL 12 . abstract: During the Ebola virus disease (EVD) epidemic in Western Africa (2013‒2016), antimalarial treatment was administered to EVD patients due to the high coexisting malaria burden in accordance with World Health Organization guidelines. In an Ebola treatment center in Liberia, EVD patients receiving the combination antimalarial artesunate-amodiaquine had a lower risk of death compared to those treated with artemether-lumefantrine. As artemether and artesunate are derivatives of artemisinin, the beneficial anti-Ebola virus (EBOV) effect observed could possibly be attributed to the change from lumefantrine to amodiaquine. Amodiaquine is a widely used antimalarial in the countries that experience outbreaks of EVD and, therefore, holds promise as an approved drug that could be repurposed for treating EBOV infections. We investigated the potential anti-EBOV effect of amodiaquine in a well-characterized nonhuman primate model of EVD. Using a similar 3-day antimalarial dosing strategy as for human patients, plasma concentrations of amodiaquine in healthy animals were similar to those found in humans. However, the treatment regimen did not result in a survival benefit or decrease of disease signs in EBOV-infected animals. While amodiaquine on its own failed to demonstrate efficacy, we cannot exclude potential therapeutic value of amodiaquine when used in combination with artesunate or another antiviral. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6934550/ doi: 10.1038/s41598-019-56481-0 id: cord-011129-btaxvmsr author: Di Paola, Nicholas title: Viral genomics in Ebola virus research date: 2020-05-04 words: 9440 sentences: 433 pages: flesch: 37 cache: ./cache/cord-011129-btaxvmsr.txt txt: ./txt/cord-011129-btaxvmsr.txt summary: Here, we review how recent advances in genomic technologies have shaped past and current responses to outbreaks of Ebola virus disease (EVD), including insights into filovirus diversity and evolution. After this identification, considerations other than sequencing speed (for example, sequencing accuracy and processivity) become paramount in determining virus transmission networks and in detecting changes in the viral genome (between cases in the current outbreak and between the current and previous outbreaks) that could subvert MCMs. However, whereas unbiased sequencing approaches using high fidelity platforms can lead to the discovery of co-infections and reveal important clinical considerations during the treatment of patients near the point of need, targeted methods of pathogen characterization using the portable sequencing platforms iSeq 100 and MiSeq (which use bait-enrichment techniques) and MinION (which uses amplicon sequencing) can still provide useful genomic data albeit with a lower sequencing output (that is, a lower number of reads) than unbiased sequencing. abstract: Filoviruses such as Ebola virus continue to pose a substantial health risk to humans. Advances in the sequencing and functional characterization of both pathogen and host genomes have provided a wealth of knowledge to clinicians, epidemiologists and public health responders during outbreaks of high-consequence viral disease. Here, we describe how genomics has been historically used to investigate Ebola virus disease outbreaks and how new technologies allow for rapid, large-scale data generation at the point of care. We highlight how genomics extends beyond consensus-level sequencing of the virus to include intra-host viral transcriptomics and the characterization of host responses in acute and persistently infected patients. Similar genomics techniques can also be applied to the characterization of non-human primate animal models and to known natural reservoirs of filoviruses, and metagenomic sequencing can be the key to the discovery of novel filoviruses. Finally, we outline the importance of reverse genetics systems that can swiftly characterize filoviruses as soon as their genome sequences are available. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223634/ doi: 10.1038/s41579-020-0354-7 id: cord-352492-6ihyiwgb author: Eickmann, Markus title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively date: 2018-05-06 words: 3005 sentences: 164 pages: flesch: 55 cache: ./cache/cord-352492-6ihyiwgb.txt txt: ./txt/cord-352492-6ihyiwgb.txt summary: title: Inactivation of Ebola virus and Middle East respiratory syndrome coronavirus in platelet concentrates and plasma by ultraviolet C light and methylene blue plus visible light, respectively STUDY DESIGN AND METHODS: PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity. The results of the infectivity assay demonstrated that UVC irradiation dose-dependently inactivated EBOV and MERS-CoV in plasma-reduced PCs (Table 1 ). Although EBOV is highly infectious and low doses of less than 10 plaque-forming units of the virus are sufficient to cause disease, 32 the ability of the UVC-and MB/ light-based systems to reduce MERS-CoV and EBOV infectivity in blood products by several log steps may be sufficient to eliminate or significantly reduce the risk of transmission via the transfusion of PCs or plasma. abstract: BACKGROUND: Ebola virus (EBOV) and Middle East respiratory syndrome coronavirus (MERS‐CoV) have been identified as potential threats to blood safety. This study investigated the efficacy of the THERAFLEX UV‐Platelets and THERAFLEX MB‐Plasma pathogen inactivation systems to inactivate EBOV and MERS‐CoV in platelet concentrates (PCs) and plasma, respectively. STUDY DESIGN AND METHODS: PCs and plasma were spiked with high titers of cell culture–derived EBOV and MERS‐CoV, treated with various light doses of ultraviolet C (UVC; THERAFLEX UV‐Platelets) or methylene blue (MB) plus visible light (MB/light; THERAFLEX MB‐Plasma), and assessed for residual viral infectivity. RESULTS: UVC reduced EBOV (≥4.5 log) and MERS‐CoV (≥3.7 log) infectivity in PCs to the limit of detection, and MB/light decreased EBOV (≥4.6 log) and MERS‐CoV (≥3.3 log) titers in plasma to nondetectable levels. CONCLUSIONS: Both THERAFLEX UV‐Platelets (UVC) and THERAFLEX MB‐Plasma (MB/light) effectively reduce EBOV and MERS‐CoV infectivity in platelets and plasma, respectively. url: https://www.ncbi.nlm.nih.gov/pubmed/29732571/ doi: 10.1111/trf.14652 id: cord-001513-p7v5p036 author: Ekins, Sean title: A common feature pharmacophore for FDA-approved drugs inhibiting the Ebola virus date: 2014-12-12 words: 4756 sentences: 250 pages: flesch: 56 cache: ./cache/cord-001513-p7v5p036.txt txt: ./txt/cord-001513-p7v5p036.txt summary: Common features pharmacophore for EBOV actives Two papers from 2013 described compounds active as inhibitors of different EBOV strains in vitro and in vivo, namely amodiaquine and chloroquine in one study 8 , clomiphene and toremifene in another 9 . These suggest that the receptor-ligand based approach results in a general similarity across the nine structures, likely indicating the similar binding mode and importance of features for interfering with this generally hydrophobic pocket for protein-protein interactions. In silico docking of molecules in VP35 structure Redocking the 4IBI ligand in the protein resulted in an RMSD of 3.02Å, which generally indicates the difficulty of predicting orientations for compounds binding in what is a relatively hydrophobic and shallow pocket ( Figure S1 ). Pharmacophores, receptor ligand models and docking data for FDA-approved drugs inhibiting the Ebola virus, 10.5256/f1000research.5741.d38449 35 . abstract: We are currently faced with a global infectious disease crisis which has been anticipated for decades. While many promising biotherapeutics are being tested, the search for a small molecule has yet to deliver an approved drug or therapeutic for the Ebola or similar filoviruses that cause haemorrhagic fever. Two recent high throughput screens published in 2013 did however identify several hits that progressed to animal studies that are FDA approved drugs used for other indications. The current computational analysis uses these molecules from two different structural classes to construct a common features pharmacophore. This ligand-based pharmacophore implicates a possible common target or mechanism that could be further explored. A recent structure based design project yielded nine co-crystal structures of pyrrolidinone inhibitors bound to the viral protein 35 (VP35). When receptor-ligand pharmacophores based on the analogs of these molecules and the protein structures were constructed, the molecular features partially overlapped with the common features of solely ligand-based pharmacophore models based on FDA approved drugs. These previously identified FDA approved drugs with activity against Ebola were therefore docked into this protein. The antimalarials chloroquine and amodiaquine docked favorably in VP35. We propose that these drugs identified to date as inhibitors of the Ebola virus may be targeting VP35. These computational models may provide preliminary insights into the molecular features that are responsible for their activity against Ebola virus in vitro and in vivo and we propose that this hypothesis could be readily tested. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4304229/ doi: 10.12688/f1000research.5741.2 id: cord-288029-6l91knu3 author: Elfiky, Abdo A. title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction date: 2020-04-14 words: 3082 sentences: 206 pages: flesch: 65 cache: ./cache/cord-288029-6l91knu3.txt txt: ./txt/cord-288029-6l91knu3.txt summary: title: Ebola virus glycoprotein GP1—host cell-surface HSPA5 binding site prediction In this study, structural and sequence analysis and molecular docking are used to predict the possible binding site between the cell-surface HSPA5 and EBOV GP1. In this work, the binding site between cell-surface HSPA5 and viral GP1 protein is predicted based on sequence, and thus, Pep42 is an example of a class of drugs that may reduce EBOV infections. In addition, HPEPDOCK constructs different possible conformations of the peptide and tests the binding affinity of each of the predicted structures against the target protein (Zhou et al. The cyclic peptide Pep42 was reported to selectively target cell-surface HSPA5 (which appears in some types of cancer) and used as a drug carrier for the anti-cancer agent, doxorubicin (Ibrahim et al. These hydrophobic residues of EBOV GP1 (C121, L122, A124, A125, I129, F132, and C135) are suggested to be the binding site for cell-surface HSPA5. Ebola virus glycoprotein GP1-host cell-surface HSPA5 binding site prediction abstract: Ebola virus (EBOV) infection is a widespread infection that has created a bad memory in Africa. In the 2014 and 2015 outbreak, more than 28,000 infections were reported by the World Health Organization, with about 11,300 deaths in Guinea, Liberia, and Sierra Leone. Heat shock protein A5 (HSPA5), termed also GRP78, is a host cell chaperone protein responsible for the unfolded protein response in the endoplasmic reticulum. Under stress, HSPA5 is upregulated and becomes cell-surface exposed. Recent studies report the association of cell-surface HSPA5 with EBOV glycoproteins GP1 and GP2. In this study, structural and sequence analysis and molecular docking are used to predict the possible binding site between the cell-surface HSPA5 and EBOV GP1. The results show a promising binding site that supports the hypothesis of HSPA5 selectivity for binding to a specific peptide sequence (pep42). This study paves the way to suggest possible inhibitors to stop viral association with cell-surface receptors and subsequently reduce viral infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12192-020-01106-z) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s12192-020-01106-z doi: 10.1007/s12192-020-01106-z id: cord-284845-on97zu6w author: Falcinelli, Shane D. title: Integration of Global Analyses of Host Molecular Responses with Clinical Data To Evaluate Pathogenesis and Advance Therapies for Emerging and Re-emerging Viral Infections date: 2016-07-29 words: 8473 sentences: 421 pages: flesch: 35 cache: ./cache/cord-284845-on97zu6w.txt txt: ./txt/cord-284845-on97zu6w.txt summary: Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. As emerging viral infections often result in severe illness including respiratory failure [severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and influenza] and multiorgan failure [Ebola virus disease (EVD)], understanding complex pathogenesis of these infections is required for effective vaccine and therapeutic design and for improved patient care. Specifically, detailed natural history studies merging multiple data streams including OMICS approaches (high-throughput gene expression and kinomics) and focused translational investigations utilizing relevant models that can be validated to human disease are needed to clarify disease pathogenesis, advance therapeutic discovery, and facilitate regulatory approval. abstract: [Image: see text] Outbreaks associated with emerging and re-emerging viral pathogens continue to increase in frequency and are associated with an increasing burden to global health. In light of this, there is a need to integrate basic and clinical research for investigating the connections between molecular and clinical pathogenesis and for therapeutic development strategies. Here, we will discuss this approach with a focus on the emerging viral pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), Ebola virus (EBOV), and monkeypox virus (MPXV) from the context of clinical presentation, immunological and molecular features of the diseases, and OMICS-based analyses of pathogenesis. Furthermore, we will highlight the role of global investigations of host kinases, the kinome, for investigating emerging and re-emerging viral pathogens from the context of characterizing cellular responses and identifying novel therapeutic targets. Lastly, we will address how increased integration of clinical and basic research will assist treatment and prevention efforts for emerging pathogens. url: https://www.ncbi.nlm.nih.gov/pubmed/27933782/ doi: 10.1021/acsinfecdis.6b00104 id: cord-289413-mbrw85og author: Flego, Michela title: Intracellular human antibody fragments recognizing the VP35 protein of Zaire Ebola filovirus inhibit the protein activity date: 2019-09-05 words: 5528 sentences: 243 pages: flesch: 47 cache: ./cache/cord-289413-mbrw85og.txt txt: ./txt/cord-289413-mbrw85og.txt summary: RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. This study reports the selection by phage display and characterization of 5 different human scFv antibodies binding to an active form of the Zaire EBOV VP35 [24, 25] . In a competitive assay, ELISA plates coated with VP35 or with the control antigen GO were blocked; they were then incubated with purified scFv-expressing phage both in the absence and in the presence of the competitor soluble non-phage-fused scFv at the maximum concentration of 500 μg/ml. abstract: BACKGROUND: Ebola hemorrhagic fever is caused by the Ebola filovirus (EBOV), which is one of the most aggressive infectious agents known worldwide. The EBOV pathogenesis starts with uncontrolled viral replication and subversion of both the innate and adaptive host immune response. The multifunctional viral VP35 protein is involved in this process by exerting an antagonistic action against the early antiviral alpha/beta interferon (IFN-α/β) response, and represents a suitable target for the development of strategies to control EBOV infection. Phage display technology permits to select antibodies as single chain Fragment variable (scFv) from an artificial immune system, due to their ability to specifically recognize the antigen of interest. ScFv is ideal for genetic manipulation and to obtain antibody constructs useful for targeting either antigens expressed on cell surface or intracellular antigens if the scFv is expressed as intracellular antibody (intrabody) or delivered into the cells. RESULTS: Monoclonal antibodies (mAb) in scFv format specific for the EBOV VP35 were isolated from the ETH-2 library of human recombinant antibodies by phage display technology. Five different clones were identified by sequencing, produced in E.coli and expressed in CHO mammalian cells to be characterized in vitro. All the selected scFvs were able to react with recombinant VP35 protein in ELISA, one of the scFvs being also able to react in Western Blot assay (WB). In addition, all scFvs were expressed in cell cytoplasm as intrabodies; a luciferase reporter gene inhibition assay performed in A549 cells showed that two of the scFvs can significantly hamper the inhibition of the IFN-β-induced RIG-I signaling cascade mediated by EBOV VP35. CONCLUSION: Five antibodies in scFv format recognize an active form of EBOV VP35 in ELISA, while one antibody also recognizes VP35 in WB. Two of these scFvs were also able to interfere with the intracellular activity of VP35 in a cell system in vitro. These findings suggest that such antibodies in scFv format might be employed to develop therapeutic molecules able to hamper EBOV infections. url: https://doi.org/10.1186/s12896-019-0554-2 doi: 10.1186/s12896-019-0554-2 id: cord-354068-4qlk6y7h author: Friedrich, Brian M. title: Potential Vaccines and Post-Exposure Treatments for Filovirus Infections date: 2012-09-21 words: 10605 sentences: 540 pages: flesch: 44 cache: ./cache/cord-354068-4qlk6y7h.txt txt: ./txt/cord-354068-4qlk6y7h.txt summary: Due to the difficulties in evaluating wild-type filovirus infection in small animals and the generally high level of immune protection correlates derived from non-human primate (NHP) models of infection, therapeutics and vaccines are ultimately evaluated in NHP species for efficacy against filovirus. In their study, a heterologous prime/boost strategy with recombinant adenovirus serotypes 26 and 35 carrying GP (Z) and GP (S/G) demonstrated complete protection among NHPs. Each of these vectors was capable of stimulating humoral and cell-mediated immune responses in the context of NHPs pre-vaccinated with rAd5 as evidenced by antibody titers reaching an order of magnitude above those achieved in rAd5 vaccinated subjects (1:32,000 compared to 1:6,800), and CD8 + intracellular cytokine staining was 4.7-fold greater among heterologous prime/boosted subjects (0.41% compared to 0.09%) [59] . This GP-Fc fusion protein induced both cell-mediated and humoral immune responses, and mice vaccinated with ZEBOVGP-Fc demonstrated 90% protection against a lethal EBOV challenge. abstract: Viruses of the family Filoviridae represent significant health risks as emerging infectious diseases as well as potentially engineered biothreats. While many research efforts have been published offering possibilities toward the mitigation of filoviral infection, there remain no sanctioned therapeutic or vaccine strategies. Current progress in the development of filovirus therapeutics and vaccines is outlined herein with respect to their current level of testing, evaluation, and proximity toward human implementation, specifically with regard to human clinical trials, nonhuman primate studies, small animal studies, and in vitro development. Contemporary methods of supportive care and previous treatment approaches for human patients are also discussed. url: https://doi.org/10.3390/v4091619 doi: 10.3390/v4091619 id: cord-004126-u6ts87ur author: Furuyama, Wakako title: A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades date: 2020-01-10 words: 6034 sentences: 333 pages: flesch: 51 cache: ./cache/cord-004126-u6ts87ur.txt txt: ./txt/cord-004126-u6ts87ur.txt summary: Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine. We found that a single vaccination with VSV-vectors expressing the full-length HA (HAfl) induced crossreactive H5-specific antibodies and conferred complete protection against lethal challenge with various H5 clade 2 viruses. In contrast to all the sHA-based vaccines, single doses of the VSV-EBOV-HAfl or VSV-HAfl vectors were sufficient to provide complete protection from lethal homologous H5N1 challenge in mice (Fig. 2) . However, this study did not provide any data supporting an advantage of including VSV-EBOV as part of the vector design over just expressing VSV-HAfl as both vectors performed similarly well with no statistically significant difference in efficacy following single-dose or prime/boost administration (Fig. 2 ) nor in antibody responses (Fig. 3, Table 1 ). abstract: The avian influenza virus outbreak in 1997 highlighted the potential of the highly pathogenic H5N1 virus to cause severe disease in humans. Therefore, effective vaccines against H5N1 viruses are needed to counter the potential threat of a global pandemic. We have previously developed a fast-acting and efficacious vaccine against Ebola virus (EBOV) using the vesicular stomatitis virus (VSV) platform. In this study, we generated recombinant VSV-based H5N1 influenza virus vectors to demonstrate the feasibility of this platform for a fast-acting pan-H5 influenza virus vaccine. We chose multiple approaches regarding antigen design and genome location to define a more optimized vaccine approach. After the VSV-based H5N1 influenza virus constructs were recovered and characterized in vitro, mice were vaccinated by a single dose or prime/boost regimen followed by challenge with a lethal dose of the homologous H5 clade 1 virus. We found that a single dose of VSV vectors expressing full-length hemagglutinin (HAfl) were sufficient to provide 100% protection. The vaccine vectors were fast-acting as demonstrated by uniform protection when administered 3 days prior to lethal challenge. Moreover, single vaccination induced cross-protective H5-specific antibodies and protected mice against lethal challenge with various H5 clade 2 viruses, highlighting the potential of the VSV-based HAfl as a pan-H5 influenza virus emergency vaccine. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954110/ doi: 10.1038/s41541-019-0155-z id: cord-335093-tc1qo2k0 author: Gehring, Gerrit title: The clinically approved drugs amiodarone, dronedarone and verapamil inhibit filovirus cell entry date: 2014-08-01 words: 5187 sentences: 267 pages: flesch: 48 cache: ./cache/cord-335093-tc1qo2k0.txt txt: ./txt/cord-335093-tc1qo2k0.txt summary: Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. While most drugs had no major effect on filovirus GP-mediated cell entry, amiodarone was found to reduce the detectable signal by over 99%, and thus more strongly than FYdmk, which achieved 86% -98% inhibition. Filoviral GP-mediated entry into primary human umbilical vein endothelial cells and in macrophages derived from primary human monocytes was significantly inhibited at amiodarone concentrations below 1 mg/mL for both MARV and EBOV GP while amiodarone had no effect on the transduction of primary hepatocytes ( Figure S3 , available as Supplementary data at JAC Online). abstract: OBJECTIVES: Filoviruses such as Ebola virus and Marburg virus cause a severe haemorrhagic fever syndrome in humans for which there is no specific treatment. Since filoviruses use a complex route of cell entry that depends on numerous cellular factors, we hypothesized that there may be drugs already approved for human use for other indications that interfere with signal transduction or other cellular processes required for their entry and hence have anti-filoviral properties. METHODS: We used authentic filoviruses and lentiviral particles pseudotyped with filoviral glycoproteins to identify and characterize such compounds. RESULTS: We discovered that amiodarone, a multi-ion channel inhibitor and adrenoceptor antagonist, is a potent inhibitor of filovirus cell entry at concentrations that are routinely reached in human serum during anti-arrhythmic therapy. A similar effect was observed with the amiodarone-related agent dronedarone and the L-type calcium channel blocker verapamil. Inhibition by amiodarone was concentration dependent and similarly affected pseudoviruses as well as authentic filoviruses. Inhibition of filovirus entry was observed with most but not all cell types tested and was accentuated by the pre-treatment of cells, indicating a host cell-directed mechanism of action. The New World arenavirus Guanarito was also inhibited by amiodarone while the Old World arenavirus Lassa and members of the Rhabdoviridae (vesicular stomatitis virus) and Bunyaviridae (Hantaan) families were largely resistant. CONCLUSIONS: The ion channel blockers amiodarone, dronedarone and verapamil inhibit filoviral cell entry. url: https://doi.org/10.1093/jac/dku091 doi: 10.1093/jac/dku091 id: cord-344316-mwnnmwnw author: Herst, C.V. title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors’ CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design date: 2020-04-28 words: 3495 sentences: 194 pages: flesch: 49 cache: ./cache/cord-344316-mwnnmwnw.txt txt: ./txt/cord-344316-mwnnmwnw.txt summary: title: An Effective CTL Peptide Vaccine for Ebola Zaire Based on Survivors'' CD8+ Targeting of a Particular Nucleocapsid Protein Epitope with Potential Implications for COVID-19 Vaccine Design An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. Wilson We set out to see if we could drive CTL expansion directed against NP43-53 to occur after vaccinating C57BL/6 mice with Ebola Zaire NP43-53 (VYQVNNLEEIC), 50 and to subsequently conduct an in-vivo EBOV challenge study to see if this peptide was protective. We show here that the H2-D b restricted epitopes VSV (RGYVYQGL) and OVA (SIINFEKL), when administered to C57BL/6 mice, each produce a CD8+ We used this adjuvanted microsphere peptide vaccine platform to immunize C57BL/6 mice with NP43-53, the CTL+ class I peptide antigen from the Ebola Ziare NP protein identified as protective by Wilson et al. abstract: The 2013-2016 West Africa EBOV epidemic was the biggest EBOV outbreak to date. An analysis of virus-specific CD8+ T-cell immunity in 30 survivors showed that 26 of those individuals had a CD8+ response to at least one EBOV protein. The dominant response (25/26 subjects) was specific to the EBOV nucleocapsid protein (NP). It has been suggested that epitopes on the EBOV NP could form an important part of an effective T-cell vaccine for Ebola Zaire. We show that a 9-amino-acid peptide NP44-52 (YQVNNLEEI) located in a conserved region of EBOV NP provides protection against morbidity and mortality after mouse adapted EBOV challenge. A single vaccination in a C57BL/6 mouse using an adjuvanted microsphere peptide vaccine formulation containing NP44-52 is enough to confer immunity in mice. Our work suggests that a peptide vaccine based on CD8+ T-cell immunity in EBOV survivors is conceptually sound and feasible. Nucleocapsid proteins within SARS-CoV-2 contain multiple class I epitopes with predicted HLA restrictions consistent with broad population coverage. A similar approach to a CTL vaccine design may be possible for that virus. url: https://www.ncbi.nlm.nih.gov/pubmed/32418793/ doi: 10.1016/j.vaccine.2020.04.034 id: cord-001764-njzyu4mv author: Hofmann-Winkler, Heike title: Comparative Analysis of Host Cell Entry of Ebola Virus From Sierra Leone, 2014, and Zaire, 1976 date: 2015-10-01 words: 4175 sentences: 202 pages: flesch: 49 cache: ./cache/cord-001764-njzyu4mv.txt txt: ./txt/cord-001764-njzyu4mv.txt summary: Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. However, EBOV-GP 2014 was less susceptible than EBOV-GP 1976 to blockade by a third inhibitor, CatL ( Figure 3B ), which inhibits catB and catL activity to similar extents [40] , suggesting subtle differences in the protease dependence of these GPs. HIV-derived particles rapidly lose infectivity when stored at room temperature [41] , and this loss might be due to inactivation of the viral envelope protein. Comparably Inhibited by IFITM Proteins and Neutralizing Antibody KZ52 IFITM proteins 1, 2, and 3 inhibit cellular entry of EBOV [42] and several other viral pathogens [42, 43] and might reduce EBOV amplification in the infected host, raising the question of whether viruses circulating in 2014 are less susceptible to IFITM protein inhibition than those responsible for the 1976 outbreak in Zaire. abstract: The ongoing Ebola virus (EBOV) disease (EVD) epidemic in Western Africa is the largest EVD outbreak recorded to date and requires the rapid development and deployment of antiviral measures. The viral glycoprotein (GP) facilitates host cell entry and, jointly with cellular interaction partners, constitutes a potential target for antiviral intervention. However, it is unknown whether the GPs of the currently and previously circulating EBOVs use the same mechanisms for cellular entry and are thus susceptible to inhibition by the same antivirals and cellular defenses. Here, we show that the GPs of the EBOVs circulating in 1976 and 2014 transduce the same spectrum of target cells, use the same cellular factors for host cell entry, and are comparably susceptible to blockade by antiviral interferon-induced transmembrane proteins and neutralizing antibody KZ52. Thus, the viruses responsible for the ongoing EVD epidemic should be fully susceptible to established antiviral strategies targeting GP and cellular entry factors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4564534/ doi: 10.1093/infdis/jiv101 id: cord-342052-v4y1xc90 author: Horigan, Verity title: Application of a quantitative entry assessment model to compare the relative risk of incursion of zoonotic bat-borne viruses into European Union Member States date: 2017-10-02 words: 12804 sentences: 611 pages: flesch: 55 cache: ./cache/cord-342052-v4y1xc90.txt txt: ./txt/cord-342052-v4y1xc90.txt summary: The use of the same framework and generic data sources for all EU Member States (MS) allows for a relative comparison of the probability of virus introduction and of the importance of the routes of introduction among MSs. According to the model wEBOV posed the highest risk of an introduction event within the EU, followed by MARV and MERS-CoV. Since 2003 there have been a number of large-scale human outbreaks of bat-borne diseases e.g. Zaire ebolavirus (EBOV) and Severe Acute Respiratory Syndrome (SARS) in Western Africa and Asia respectively, whilst a significant number of human cases of Nipah virus (NiV) are reported in Bangladesh every year (IEDCR, 2014) . To address this need, a generic quantitative risk assessment framework for the entry of bat-borne zoonotic viruses to the EU was developed (Simons et al., 2016) , considering the pathways: human travel, live animal movement, legal trade of food products and illegal trade of bushmeat. abstract: This paper presents a quantitative assessment model for the risk of entry of zoonotic bat-borne viruses into the European Union (EU). The model considers four routes of introduction: human travel, legal trade of products, live animal imports and illegal import of bushmeat and was applied to five virus outbreak scenarios. Two scenarios were considered for Zaire ebolavirus (wEBOV, cEBOV) and other scenarios for Hendra virus, Marburg virus (MARV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV). The use of the same framework and generic data sources for all EU Member States (MS) allows for a relative comparison of the probability of virus introduction and of the importance of the routes of introduction among MSs. According to the model wEBOV posed the highest risk of an introduction event within the EU, followed by MARV and MERS-CoV. However, the main route of introduction differed, with wEBOV and MERS-CoV most likely through human travel and MARV through legal trade of foodstuffs. The relative risks to EU MSs as entry points also varied between outbreak scenarios, highlighting the heterogeneity in global trade and travel to the EU MSs. The model has the capability to allow for a continual updating of the risk estimate using new data as, and when, it becomes available. The model provides an horizon scanning tool for use when available data are limited and, therefore, the absolute risk estimates often have high uncertainty. Sensitivity analysis suggested virus prevalence in bats has a large influence on the results; a 90% reduction in prevalence reduced the risk of introduction considerably and resulted in the relative ranking of MARV falling below that for MERS-CoV, due to this parameter disproportionately affecting the risk of introduction from the trade route over human travel. url: https://api.elsevier.com/content/article/pii/S2352352217301408 doi: 10.1016/j.mran.2017.09.002 id: cord-334560-1j9zmuub author: Hunt, Catherine L. title: Filovirus Entry: A Novelty in the Viral Fusion World date: 2012-02-07 words: 6445 sentences: 301 pages: flesch: 48 cache: ./cache/cord-334560-1j9zmuub.txt txt: ./txt/cord-334560-1j9zmuub.txt summary: Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. However, for reasons that are not entirely clear, this type of study has not been successful in identifying cell surface proteins that directly interact with EBOV GP to mediate virus entry [41, 42] . However, as both of these regions can be deleted from EBOV GP 1 without loss of viral transduction efficiency [16, [50] [51] [52] , it is likely that C-type lectins increase filovirus attachment to cells rather than serving as cellular receptors that mediate internalization of the virus into endosomes [53] . abstract: Ebolavirus (EBOV) and Marburgvirus (MARV) that compose the filovirus family of negative strand RNA viruses infect a broad range of mammalian cells. Recent studies indicate that cellular entry of this family of viruses requires a series of cellular protein interactions and molecular mechanisms, some of which are unique to filoviruses and others are commonly used by all viral glycoproteins. Details of this entry pathway are highlighted here. Virus entry into cells is initiated by the interaction of the viral glycoprotein(1) subunit (GP(1)) with both adherence factors and one or more receptors on the surface of host cells. On epithelial cells, we recently demonstrated that TIM-1 serves as a receptor for this family of viruses, but the cell surface receptors in other cell types remain unidentified. Upon receptor binding, the virus is internalized into endosomes primarily via macropinocytosis, but perhaps by other mechanisms as well. Within the acidified endosome, the heavily glycosylated GP(1) is cleaved to a smaller form by the low pH-dependent cellular proteases Cathepsin L and B, exposing residues in the receptor binding site (RBS). Details of the molecular events following cathepsin-dependent trimming of GP(1) are currently incomplete; however, the processed GP(1) specifically interacts with endosomal/lysosomal membranes that contain the Niemann Pick C1 (NPC1) protein and expression of NPC1 is required for productive infection, suggesting that GP/NPC1 interactions may be an important late step in the entry process. Additional events such as further GP(1) processing and/or reducing events may also be required to generate a fusion-ready form of the glycoprotein. Once this has been achieved, sequences in the filovirus GP(2) subunit mediate viral/cellular membrane fusion via mechanisms similar to those previously described for other enveloped viruses. This multi-step entry pathway highlights the complex and highly orchestrated path of internalization and fusion that appears unique for filoviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/22470835/ doi: 10.3390/v4020258 id: cord-327641-hqnem2zs author: Ji, Ying-Jie title: Clinical presentations and outcomes of patients with Ebola virus disease in Freetown, Sierra Leone date: 2016-11-03 words: 5871 sentences: 300 pages: flesch: 57 cache: ./cache/cord-327641-hqnem2zs.txt txt: ./txt/cord-327641-hqnem2zs.txt summary: BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. In the 2014 outbreak, the first lab-confirmed EVD patient was reported in May, 2014 in Guinea and since then the Zaire Ebola Virus (ZEBOV) has rapidly spread across Sierra Leone and to other West Africa countries. A retrospective, observational study was conducted using data collected from all patients with confirmed EVD who were admitted to the Holding and Treatment Center of Jui Government Hospital from October 1, 2014 to March 21, 2015. In our study, the multivariate analyses showed that EBOV viral load, abdominal pain, confusion, conjunctivitis, and vomiting were independently associated with the death outcome of EVD patients. abstract: BACKGROUND: Clinical and laboratory data were collected and analysed from patients with Ebola virus disease (EVD) in Jui Government Hospital in Freetown, Sierra Leone, where patients with EVD were received and/or treated from October 1, 2014 to March 21, 2015 during the West Africa EVD outbreak. METHODS: The study admitted 285 patients with confirmed EVD and followed them up till the endpoint (recovery or death). EVD was confirmed by quantitative RT-PCR assays detecting blood Ebola virus (EBOV). RESULTS: Among the 285 lab-confirmed EVD cases in Jui Government Hospital, 146 recovered and 139 died, with an overall survival rate of 51.23 %. Patients under the age of 6 years had a lower survival rate (37.50 %). Most non-survivors (79.86 %) died within 7 days after admission and the mean hospitalization time for non-survivors was 5.56 ± 6.11 days. More than half survivors (63.69 %) turned blood EBOV negative within 3 weeks after admission and the mean hospitalization time for survivors was 20.38 ± 7.58 days. High blood viral load (≥10(6) copies/ml) was found to be predictive of the non-survival outcome as indicated by the Receiver Operating Characteristic (ROC) curve analysis. The probability of patients’ survival was less than 15 % when blood viral load was greater than 10(6) copies/ml. Multivariate analyses showed that blood viral load (P = 0.005), confusion (P = 0.010), abdominal pain (P = 0.003), conjunctivitis (P = 0.035), and vomiting (P = 0.004) were factors independently associated with the outcomes of EVD patients. CONCLUSIONS: Most death occurred within 1 week after admission, and patients at the age of 6 or younger had a lower survival rate. Most surviving patients turned blood EBOV negative within 1–4 weeks after admission. Factors such as high blood viral load, confusion, abdominal pain, vomiting and conjunctivitis were associated with poor prognosis for EVD patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40249-016-0195-9) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pubmed/27806732/ doi: 10.1186/s40249-016-0195-9 id: cord-256187-ofp7tupv author: Kühl, A. title: How Ebola Virus Counters the Interferon System date: 2012-09-07 words: 8609 sentences: 439 pages: flesch: 49 cache: ./cache/cord-256187-ofp7tupv.txt txt: ./txt/cord-256187-ofp7tupv.txt summary: Furthermore, VP24 can shut down the host''s IFN-a/b and IFN-c Recognition of viral pathogen-associated molecular patterns (PAMPs) by PRRs (purple) in infected cells initiates a signalling cascade including adaptor molecules (blue) and kinases (green), which activate transcription factors (red) that induce the expression of type I IFNs and ISGs (left panel). Additionally, VP35 blocks multiple steps of the innate antiviral defence (Fig. 4) , such as the signalling pathways leading to the expression of type I IFNs and type I IFN-induced genes, double-stranded (ds) RNA-dependent protein kinase (PKR) translation inhibition and RNA silencing Cárdenas et al., 2006; Feng et al., 2007; Haasnoot et al., 2007) . The tetherin protein (HM1.24, BST-2, CD317) was identified as a type I interferon-inducible host cellular factor, which restricts release of progeny HIV-1 particles from infected cells (Neil et al., 2008; Van Damme et al., 2008) . abstract: Zoonotic transmission of Ebola virus (EBOV) to humans causes a severe haemorrhagic fever in afflicted individuals with high case‐fatality rates. Neither vaccines nor therapeutics are at present available to combat EBOV infection, making the virus a potential threat to public health. To devise antiviral strategies, it is important to understand which components of the immune system could be effective against EBOV infection. The interferon (IFN) system constitutes a key innate defence against viral infections and prevents development of lethal disease in mice infected with EBOV strains not adapted to this host. Recent research revealed that expression of the host cell IFN‐inducible transmembrane proteins 1–3 (IFITM1–3) and tetherin is induced by IFN and restricts EBOV infection, at least in cell culture model systems. IFITMs, tetherin and other effector molecules of the IFN system could thus pose a potent barrier against EBOV spread in humans. However, EBOV interferes with signalling events required for human cells to express these proteins. Here, we will review the strategies employed by EBOV to fight the IFN system, and we will discuss how IFITM proteins and tetherin inhibit EBOV infection. url: https://doi.org/10.1111/j.1863-2378.2012.01454.x doi: 10.1111/j.1863-2378.2012.01454.x id: cord-001542-f089bs8r author: Lai, Kang Yiu title: Human Ebola virus infection in West Africa: a review of available therapeutic agents that target different steps of the life cycle of Ebola virus date: 2014-11-28 words: 11274 sentences: 604 pages: flesch: 42 cache: ./cache/cord-001542-f089bs8r.txt txt: ./txt/cord-001542-f089bs8r.txt summary: These may include monoclonal antibody (mAbs)-based therapies (e.g. ZMapp), anti-sense phosphorodiamidate morpholino oligomers (PMO AVI-6002), lipid nanoparticle small interfering RNA (LNP-siRNA: TKM-Ebola), and an EBOV glycoprotein-based vaccine using live-attenuated recombinant vesicular stomatitis virus (rVSV-EBOGP) or a chimpanzee adenovirus (rChAd-EBOGP)-based vector. The GP2 of the EBOV is able to counter the interferon (IFN)-inducible antiviral protein tetherin which restricts the VP40-dependent budding of the progeny viral particles from infected cells [16] [17] [18] . Currently available therapeutic agents that are effective in targeting the EBOV infection in cell or animal studies may include convalescent plasma, favipiravir, chloroquine, amiodarone, dronedarone, verapamil, clomiphene, toremifene, IFN-β, Na + /K + exchangers, Na + /K + -ATPase pump inhibitors, and antioxidants. The anti-EBOV activity of clomiphene and toremifene is dependent not on its estrogen receptor antagonistic action but upon the ability of both drugs to induce a Niemann-Pick C-like phenotype to inhibit viral entry at late endosome. abstract: The recent outbreak of the human Zaire ebolavirus (EBOV) epidemic is spiraling out of control in West Africa. Human EBOV hemorrhagic fever has a case fatality rate of up to 90%. The EBOV is classified as a biosafety level 4 pathogen and is considered a category A agent of bioterrorism by Centers for Disease Control and Prevention, with no approved therapies and vaccines available for its treatment apart from supportive care. Although several promising therapeutic agents and vaccines against EBOV are undergoing the Phase I human trial, the current epidemic might be outpacing the speed at which drugs and vaccines can be produced. Like all viruses, the EBOV largely relies on host cell factors and physiological processes for its entry, replication, and egress. We have reviewed currently available therapeutic agents that have been shown to be effective in suppressing the proliferation of the EBOV in cell cultures or animal studies. Most of the therapeutic agents in this review are directed against non-mutable targets of the host, which is independent of viral mutation. These medications are approved by the Food and Drug Administration (FDA) for the treatment of other diseases. They are available and stockpileable for immediate use. They may also have a complementary role to those therapeutic agents under development that are directed against the mutable targets of the EBOV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/2049-9957-3-43) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334593/ doi: 10.1186/2049-9957-3-43 id: cord-003917-bswndfvk author: Lalle, Eleonora title: Pulmonary Involvement during the Ebola Virus Disease date: 2019-08-24 words: 5545 sentences: 245 pages: flesch: 40 cache: ./cache/cord-003917-bswndfvk.txt txt: ./txt/cord-003917-bswndfvk.txt summary: Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . However, new evidences collected during the recent 2013-2016 Ebola outbreak hypothesized shedding of the virus in the lung and identified viral replication markers in sputum samples collected from EBOV infected patients [14] . Interestingly, evidence collected in animal studies, in the epidemiological analysis of transmission chains, and in the most recent Ebola outbreaks suggests that EBOV may be able to cause primary pulmonary infection. abstract: Filoviruses have become a worldwide public health concern, especially during the 2013–2016 Western Africa Ebola virus disease (EVD) outbreak—the largest outbreak, both by number of cases and geographical extension, recorded so far in medical history. EVD is associated with pathologies in several organs, including the liver, kidney, and lung. During the 2013–2016 Western Africa outbreak, Ebola virus (EBOV) was detected in the lung of infected patients suggesting a role in lung pathogenesis. However, little is known about lung pathogenesis and the controversial issue of aerosol transmission in EVD. This review highlights the pulmonary involvement in EVD, with a special focus on the new data emerging from the 2013–2016 Ebola outbreak. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6784166/ doi: 10.3390/v11090780 id: cord-002500-9p2n8tjx author: Lambe, Teresa title: A review of Phase I trials of Ebola virus vaccines: what can we learn from the race to develop novel vaccines? date: 2017-05-26 words: 7327 sentences: 288 pages: flesch: 38 cache: ./cache/cord-002500-9p2n8tjx.txt txt: ./txt/cord-002500-9p2n8tjx.txt summary: The other vaccine modality being assessed as an Ebola vaccine candidate is the recombinant vesicular stomatitis virus encoding EBOV glycoprotein (rVSV-ZEBOV), which is an attenuated replication-competent viral vector. In the absence of any gold standard for measuring humoral immunity against Ebola virus, a wide variety of assays were used to evaluate antibody responses to vaccines during the recent EVD outbreak. Many of the other binding assays used in these Phase I trials correlate strongly and, in particular, it is useful that the standardized glycoprotein ELISA and pseudotyped lentivirus assays each correlate strongly with neutralizing titres against live Ebola virus as these assays avoid the need to work at high containment levels, but may be used to indicate the presence of antibodies with neutralizing activity. In a pre-clinical NHP model, IgG responses after immunization with AdHu5-based Ebola virus vaccines were measured using an ELISA against GP, where 100% protection against a lethal challenge was predicted by titres of 3700 or greater, while a titre of around 2000 predicted 85% survival. abstract: Sporadic outbreaks of Ebola virus infection have been documented since the mid-Seventies and viral exposure can lead to lethal haemorrhagic fever with case fatalities as high as 90%. There is now a comprehensive body of data from both ongoing and completed clinical trials assessing various vaccine strategies, which were rapidly advanced through clinical trials in response to the 2013–2016 Ebola virus disease (EVD) public health emergency. Careful consideration of immunogenicity post vaccination is essential but has been somewhat stifled because of the wide array of immunological assays and outputs that have been used in the numerous clinical trials. We discuss here the different aspects of the immune assays currently used in the Phase I clinical trials for Ebola virus vaccines, and draw comparisons across the immune outputs where possible; various trials have examined both cellular and humoral immunity in European and African cohorts. Assessment of the safety data, the immunological outputs and the ease of field deployment for the various vaccine modalities will help both the scientific community and policy-makers prioritize and potentially license vaccine candidates. If this can be achieved, the next outbreak of Ebola virus, or other emerging pathogen, can be more readily contained and will not have such widespread and devastating consequences. This article is part of the themed issue ‘The 2013–2016 West African Ebola epidemic: data, decision-making and disease control’. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5394635/ doi: 10.1098/rstb.2016.0295 id: cord-350565-mejd7blb author: Lewnard, Joseph A title: Emerging Challenges and Opportunities in Infectious Disease Epidemiology date: 2019-03-16 words: 6614 sentences: 289 pages: flesch: 29 cache: ./cache/cord-350565-mejd7blb.txt txt: ./txt/cord-350565-mejd7blb.txt summary: We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. Although serosurveys have bolstered recent efforts to understand the geographic range and clinical spectrum of EBOV and Zika virus infections (47, 48) , the enhancement of dengue hemorrhagic fever risk by prior exposure (49) , and the role of immunologic history in influenza susceptibility and vaccine response (50) , there remain few examples of public health programs undertaking serological studies for routine surveillance, at least in civilian populations (51) . abstract: Much of the intellectual tradition of modern epidemiology stems from efforts to understand and combat chronic diseases persisting through the 20th century epidemiologic transition of countries such as the United States and United Kingdom. After decades of relative obscurity, infectious disease epidemiology has undergone an intellectual rebirth in recent years amid increasing recognition of the threat posed by both new and familiar pathogens. Here, we review the emerging coalescence of infectious disease epidemiology around a core set of study designs and statistical methods bearing little resemblance to the chronic disease epidemiology toolkit. We offer our outlook on challenges and opportunities facing the field, including the integration of novel molecular and digital information sources into disease surveillance, the assimilation of such data into models of pathogen spread, and the increasing contribution of models to public health practice. We next consider emerging paradigms in causal inference for infectious diseases, ranging from approaches to evaluating vaccines and antimicrobial therapies to the task of ascribing clinical syndromes to etiologic microorganisms, an age-old problem transformed by our increasing ability to characterize human-associated microbiota. These areas represent an increasingly important component of epidemiology training programs for future generations of researchers and practitioners. url: https://doi.org/10.1093/aje/kwy264 doi: 10.1093/aje/kwy264 id: cord-276437-5gkdotvt author: Liu, William J. title: Intra-host Ebola viral adaption during human infection date: 2019-02-20 words: 5115 sentences: 251 pages: flesch: 54 cache: ./cache/cord-276437-5gkdotvt.txt txt: ./txt/cord-276437-5gkdotvt.txt summary: EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Recent studies also showed that, during the epidemic, the EBOV isolates from early in the outbreak with amino acid substitutions in the GP protein possessed increased tropism for human cells, indicating human adaptation of Ebola virus during human-to-human transmission [19] [20] [21] . In a single patient, genome sequences obtained from samples during earlier stages of the acute infection phase possessed Ts at the 13 TNC positions, whereas Cs were found from samples collected during the recovery process. Our data indicate that short stretches of TNC substitutions are part of the convergent evolution during the infection process of EVD patients, shedding light on the dynamic intra-host genomic variation of EBOV during the 2013-2016 epidemic. abstract: The onsite next generation sequencing (NGS) of Ebola virus (EBOV) genomes during the 2013–2016 Ebola epidemic in Western Africa provides an opportunity to trace the origin, transmission, and evolution of this virus. Herein, we have diagnosed a cohort of EBOV patients in Sierra Leone in 2015, during the late phase of the outbreak. The surviving EBOV patients had a recovery process characterized by decreasing viremia, fever, and biochemical parameters. EBOV genomes sequenced through the longitudinal blood samples of these patients showed dynamic intra-host substitutions of the virus during acute infection, including the previously described short stretches of 13 serial T>C mutations. Remarkably, within individual patients, samples collected during the early phase of infection possessed Ts at these nucleotide sites, whereas they were replaced by Cs in samples collected in the later phase, suggesting that these short stretches of T>C mutations could emerge independently. In addition, up to a total of 35 nucleotide sites spanning the EBOV genome were mutated coincidently. Our study showed the dynamic intra-host adaptation of EBOV during patient recovery and gave more insight into the complex EBOV-host interactions. url: https://www.ncbi.nlm.nih.gov/pubmed/32835207/ doi: 10.1016/j.bsheal.2019.02.001 id: cord-274377-57zy6unz author: Long, Jason title: Antiviral therapies against Ebola and other emerging viral diseases using existing medicines that block virus entry date: 2015-02-10 words: 3938 sentences: 205 pages: flesch: 54 cache: ./cache/cord-274377-57zy6unz.txt txt: ./txt/cord-274377-57zy6unz.txt summary: To this end we re-examined the anti-viral properties of CQ, and show here that it inhibited the pH-dependent endosomal entry of a pseudotyped virus (PV) bearing EBOV glycoproteins, in the same way as did the potent and specific vacuolar-ATPase (vATPase) inhibitor bafilyomycin A1 (BafA1) (a non-medical laboratory compound). We also show that licensed and widely used proton pump inhibitors (PPIs) for treatment of gastric acid reflux, omeprazole (OM) and esomeprazole (ESOM), inhibited PV EBOV entry, likely by their off-target inhibitory activity on endosomal vATPase. In this instance, a ''fusion inhibitor'' could target the host cell machinery preventing acidification of the endosome, working to inhibit virus entry of several different viruses. Given the volume of research suggesting these off target effects depend on an ability to affect intracellular pH, we hypothesised that these drugs would, like CQ and BafA1, inhibit EBOV, MARV and influenza virus pH dependent entry. abstract: Emerging viral diseases pose a threat to the global population as intervention strategies are mainly limited to basic containment due to the lack of efficacious and approved vaccines and antiviral drugs. The former was the only available intervention when the current unprecedented Ebolavirus (EBOV) outbreak in West Africa began. Prior to this, the development of EBOV vaccines and anti-viral therapies required time and resources that were not available. Therefore, focus has turned to re-purposing of existing, licenced medicines that may limit the morbidity and mortality rates of EBOV and could be used immediately. Here we test three such medicines and measure their ability to inhibit pseudotype viruses (PVs) of two EBOV species, Marburg virus (MARV) and avian influenza H5 (FLU-H5). We confirm the ability of chloroquine (CQ) to inhibit viral entry in a pH specific manner. The commonly used proton pump inhibitors, Omeprazole and Esomeprazole were also able to inhibit entry of all PVs tested but at higher drug concentrations than may be achieved in vivo. We propose CQ as a priority candidate to consider for treatment of EBOV. url: https://www.ncbi.nlm.nih.gov/pubmed/26069727/ doi: 10.12688/f1000research.6085.2 id: cord-293481-bmfj50fb author: Malin, Jakob J. title: Remdesivir against COVID-19 and Other Viral Diseases date: 2020-10-14 words: 9097 sentences: 428 pages: flesch: 42 cache: ./cache/cord-293481-bmfj50fb.txt txt: ./txt/cord-293481-bmfj50fb.txt summary: Remdesivir or GS-5734 is a prodrug of a nucleoside analog with direct antiviral activity against several single-stranded RNA viruses, including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Recently, preliminary data from a randomized placebo-controlled clinical trial showed that remdesivir reduces the time to recovery in patients with COVID-19 (5) , leading to an emergency-use authorization (EUA) by the U.S. Food and Drug Administration (FDA) only 2 days after the first press release from the National Institute of Allergy and Infectious Diseases (NIAID) (6) . There were strong arguments for the antiviral effect of remdesivir against coronaviruses emerging from multiple cell-based in vitro models, including primary human airway epithelial (HAE) cell cultures (25) , and, for MERS-CoV, from a mouse model of pulmonary infection (28) . After the outbreak of SARS-CoV-2 in January 2020, remdesivir was rapidly tested in a Vero E6 cell-based model that made use of direct viral quantification by rtPCR along with the antimalaria and immune-modulating drug chloroquine and known antivirals such as ribavirin and penciclovir. abstract: Patients and physicians worldwide are facing tremendous health care hazards that are caused by the ongoing severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2) pandemic. Remdesivir (GS-5734) is the first approved treatment for severe coronavirus disease 2019 (COVID-19). It is a novel nucleoside analog with a broad antiviral activity spectrum among RNA viruses, including ebolavirus (EBOV) and the respiratory pathogens Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV, and SARS-CoV-2. First described in 2016, the drug was derived from an antiviral library of small molecules intended to target emerging pathogenic RNA viruses. In vivo, remdesivir showed therapeutic and prophylactic effects in animal models of EBOV, MERS-CoV, SARS-CoV, and SARS-CoV-2 infection. However, the substance failed in a clinical trial on ebolavirus disease (EVD), where it was inferior to investigational monoclonal antibodies in an interim analysis. As there was no placebo control in this study, no conclusions on its efficacy in EVD can be made. In contrast, data from a placebo-controlled trial show beneficial effects for patients with COVID-19. Remdesivir reduces the time to recovery of hospitalized patients who require supplemental oxygen and may have a positive impact on mortality outcomes while having a favorable safety profile. Although this is an important milestone in the fight against COVID-19, approval of this drug will not be sufficient to solve the public health issues caused by the ongoing pandemic. Further scientific efforts are needed to evaluate the full potential of nucleoside analogs as treatment or prophylaxis of viral respiratory infections and to develop effective antivirals that are orally bioavailable. url: https://doi.org/10.1128/cmr.00162-20 doi: 10.1128/cmr.00162-20 id: cord-294342-7ycgd0h7 author: Markosyan, Ruben M. title: Induction of Cell-Cell Fusion by Ebola Virus Glycoprotein: Low pH Is Not a Trigger date: 2016-01-05 words: 11740 sentences: 548 pages: flesch: 56 cache: ./cache/cord-294342-7ycgd0h7.txt txt: ./txt/cord-294342-7ycgd0h7.txt summary: On the question of low pH, we found that activation of cathepsins by acidity is the sole cause for augmentation of fusion: if EBOV GP on the cell surface is artificially cleaved by thermolysin in the presence of cathepsin inhibitors, the extent of fusion is independent of pH. We used thermolysin-treated effector cells to maximize cleavage of EBOV GP and found that adding CPZ either 30, 45, or 60 min after reneutralization did not induce any dye spread above that already observed, strongly indicating that a negligible percentage of cells were hemifused, but not fused, at any given time. The extent of fusion was greater when the inhibitor was not added (control): this indicates that delivery to the cell surface of EBOV GP cleaved by endosomal cathepsin (subsequent to thermolysin treatment) significantly contributes to fusion. abstract: Ebola virus (EBOV) is a highly pathogenic filovirus that causes hemorrhagic fever in humans and animals. Currently, how EBOV fuses its envelope membrane within an endosomal membrane to cause infection is poorly understood. We successfully measure cell-cell fusion mediated by the EBOV fusion protein, GP, assayed by the transfer of both cytoplasmic and membrane dyes. A small molecule fusion inhibitor, a neutralizing antibody, as well as mutations in EBOV GP known to reduce viral infection, all greatly reduce fusion. By monitoring redistribution of small aqueous dyes between cells and by electrical capacitance measurements, we discovered that EBOV GP-mediated fusion pores do not readily enlarge—a marked difference from the behavior of other viral fusion proteins. EBOV GP must be cleaved by late endosome-resident cathepsins B or L in order to become fusion-competent. Cleavage of cell surface-expressed GP appears to occur in endosomes, as evidenced by the fusion block imposed by cathepsin inhibitors, agents that raise endosomal pH, or an inhibitor of anterograde trafficking. Treating effector cells with a recombinant soluble cathepsin B or thermolysin, which cleaves GP into an active form, increases the extent of fusion, suggesting that a fraction of surface-expressed GP is not cleaved. Whereas the rate of fusion is increased by a brief exposure to acidic pH, fusion does occur at neutral pH. Importantly, the extent of fusion is independent of external pH in experiments in which cathepsin activity is blocked and EBOV GP is cleaved by thermolysin. These results imply that low pH promotes fusion through the well-known pH-dependent activity of cathepsins; fusion induced by cleaved EBOV GP is a process that is fundamentally independent of pH. The cell-cell fusion system has revealed some previously unappreciated features of EBOV entry, which could not be readily elucidated in the context of endosomal entry. url: https://doi.org/10.1371/journal.ppat.1005373 doi: 10.1371/journal.ppat.1005373 id: cord-300133-yc2wxgid author: Martínez, Miguel J. title: Ebola Virus Infection: Overview and Update on Prevention and Treatment date: 2015-09-12 words: 4302 sentences: 243 pages: flesch: 50 cache: ./cache/cord-300133-yc2wxgid.txt txt: ./txt/cord-300133-yc2wxgid.txt summary: In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Over the past 17 months, the West Africa EVD outbreak has provided an important opportunity to consider use of and evaluate several therapeutic and prophylactic agents (e.g., vaccines) to determine their safety and efficacy [5, 6] . FGI-103, FGI-104, and FGI-106 are a group of broad-spectrum antiviral agents that inhibit viral replication in a dose-dependent manner among multiple and genetically distinct viruses including EBOV, bunyaviruses, dengue virus, Use of convalescent whole blood or plasma collected from patients recovered from Ebola virus disease for transfusion, as an emprical treatment during outbreaks abstract: In 2014 and 2015, the largest Ebola virus disease (EVD) outbreak in history affected large populations across West Africa. The goal of this report is to provide an update on the epidemic and review current progress in the development, evaluation and deployment of prevention and treatment strategies for EVD. Relevant information was identified through a comprehensive literature search using Medline, PubMed and CINAHL Complete and using the search terms Ebola, Ebola virus disease, Ebola hemorrhagic fever, West Africa outbreak, Ebola transmission, Ebola symptoms and signs, Ebola diagnosis, Ebola treatment, vaccines for Ebola and clinical trials on Ebola. Through 22 July 2015, a total of 27,741 EVD cases and 11,284 deaths were reported from all affected countries. Several therapeutic agents and novel vaccines for EVD have been developed and are now undergoing evaluation. Concurrent with active case investigation, contact tracing, surveillance and supportive care to patients and communities, there has been rapid progress in the development of new therapies and vaccines against EVD. Continued focus on strengthening clinical and public health infrastructure will have direct benefits in controlling the spread of EVD and will provide a strong foundation for deployment of new drugs and vaccines to affected countries when they become available. The unprecedented West Africa Ebola outbreak, response measures, and ensuing drug and vaccine development suggest that new tools for Ebola control may be available in the near future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s40121-015-0079-5) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1007/s40121-015-0079-5 doi: 10.1007/s40121-015-0079-5 id: cord-288734-xinkqs6u author: Muñoz-Fontela, César title: Ebola Virus Disease in Humans: Pathophysiology and Immunity date: 2017-03-30 words: 9957 sentences: 451 pages: flesch: 44 cache: ./cache/cord-288734-xinkqs6u.txt txt: ./txt/cord-288734-xinkqs6u.txt summary: Discovered in 1976 during the first documented outbreak of Ebola virus disease (EVD) in the town of Yambuku in northern Zaire (today Democratic Republic of the Congo), EBOV has since caused sporadic human disease outbreaks of varying magnitude in Equatorial African countries (Sanchez et al. Antigen-presenting cells are a putative initial target of EBOV infection and previous research in animal models of disease has indicated that dendritic cells (DCs) and macrophages are early and preferred targets of EBOV and support virus replication (Geisbert et al. Clinical presentation, biochemical, and haematological parameters and their association with outcome in patients with Ebola virus disease: an observational cohort study Sequence-based human leukocyte antigen-B typing of patients infected with Ebola virus in Uganda in 2000: identification of alleles associated with fatal and nonfatal disease outcomes abstract: Viruses of the Ebolavirus genus cause sporadic epidemics of severe and systemic febrile disease that are fueled by human-to-human transmission. Despite the notoriety of ebolaviruses, particularly Ebola virus (EBOV), as prominent viral hemorrhagic fever agents, and the international concern regarding Ebola virus disease (EVD) outbreaks, very little is known about the pathophysiology of EVD in humans and, in particular, about the human immune correlates of survival and immune memory. This lack of basic knowledge about physiological characteristics of EVD is probably attributable to the dearth of clinical and laboratory data gathered from past outbreaks. The unprecedented magnitude of the EVD epidemic that occurred in West Africa from 2013 to 2016 has allowed, for the first time, evaluation of clinical, epidemiological, and immunological parameters in a significant number of patients using state-of-the-art laboratory equipment. This review will summarize the data from the literature regarding human pathophysiologic and immunologic responses to filoviral infection. url: https://doi.org/10.1007/82_2017_11 doi: 10.1007/82_2017_11 id: cord-279152-yh7x7w2q author: Ndungo, Esther title: A Single Residue in Ebola Virus Receptor NPC1 Influences Cellular Host Range in Reptiles date: 2016-03-30 words: 5230 sentences: 243 pages: flesch: 49 cache: ./cache/cord-279152-yh7x7w2q.txt txt: ./txt/cord-279152-yh7x7w2q.txt summary: Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. We also found that NPC1 could influence the cellular host range of filoviruses-human NPC1 conferred susceptibility to filovirus entry and infection when expressed in the nonpermissive reptilian cell line VH-2, derived from a Russell''s viper (Daboia russellii) (22) . These findings provide additional evidence that NPC1-encoded residue 503 influences the cellular host range of EBOV at the level of virus-receptor recognition and raise the possibility that sequence differences at this position influence the susceptibility of reptiles to filovirus infection in nature. abstract: Filoviruses are the causative agents of an increasing number of disease outbreaks in human populations, including the current unprecedented Ebola virus disease (EVD) outbreak in western Africa. One obstacle to controlling these epidemics is our poor understanding of the host range of filoviruses and their natural reservoirs. Here, we investigated the role of the intracellular filovirus receptor, Niemann-Pick C1 (NPC1) as a molecular determinant of Ebola virus (EBOV) host range at the cellular level. Whereas human cells can be infected by EBOV, a cell line derived from a Russell’s viper (Daboia russellii) (VH-2) is resistant to infection in an NPC1-dependent manner. We found that VH-2 cells are resistant to EBOV infection because the Russell’s viper NPC1 ortholog bound poorly to the EBOV spike glycoprotein (GP). Analysis of panels of viper-human NPC1 chimeras and point mutants allowed us to identify a single amino acid residue in NPC1, at position 503, that bidirectionally influenced both its binding to EBOV GP and its viral receptor activity in cells. Significantly, this single residue change perturbed neither NPC1’s endosomal localization nor its housekeeping role in cellular cholesterol trafficking. Together with other recent work, these findings identify sequences in NPC1 that are important for viral receptor activity by virtue of their direct interaction with EBOV GP and suggest that they may influence filovirus host range in nature. Broader surveys of NPC1 orthologs from vertebrates may delineate additional sequence polymorphisms in this gene that control susceptibility to filovirus infection. IMPORTANCE Identifying cellular factors that determine susceptibility to infection can help us understand how Ebola virus is transmitted. We asked if the EBOV receptor Niemann-Pick C1 (NPC1) could explain why reptiles are resistant to EBOV infection. We demonstrate that cells derived from the Russell’s viper are not susceptible to infection because EBOV cannot bind to viper NPC1. This resistance to infection can be mapped to a single amino acid residue in viper NPC1 that renders it unable to bind to EBOV GP. The newly solved structure of EBOV GP bound to NPC1 confirms our findings, revealing that this residue dips into the GP receptor-binding pocket and is therefore critical to the binding interface. Consequently, this otherwise well-conserved residue in vertebrate species influences the ability of reptilian NPC1 proteins to bind to EBOV GP, thereby affecting viral host range in reptilian cells. url: https://www.ncbi.nlm.nih.gov/pubmed/27303731/ doi: 10.1128/msphere.00007-16 id: cord-002185-oz7hras7 author: Nelson, Elizabeth A. title: Clomiphene and Its Isomers Block Ebola Virus Particle Entry and Infection with Similar Potency: Potential Therapeutic Implications date: 2016-08-02 words: 5047 sentences: 249 pages: flesch: 52 cache: ./cache/cord-002185-oz7hras7.txt txt: ./txt/cord-002185-oz7hras7.txt summary: In this system, 4-hydroxy-zuclomiphene appeared more potent than the Our previous findings indicated that clomiphene blocks EBOV infection by blocking entry of viral particles into the cell cytoplasm [20, 29] ; this effect appears to be at the level of fusion between the membrane of the viral particle and the limiting membrane of an Niemann-Pick disease, type C1 positive (NPC1 + ) endolysosome, the site of EBOV fusion [30] [31] [32] . Similar results were seen when comparing eight doses of clomiphene and zuclomiphene in trVLP infection ( Figure 5A ) and VLP entry ( Figure 5B ) assays. Where tested, they were equally effective to each other in two cell types and for entry mediated by three filoviral GPs. 4-hydroxy-enclomiphene, and 4-hydroxy-zuclomiphene also blocked EBOV trVLP infection and VLP entry under the abstract: The 2014 outbreak of Ebola virus (EBOV) in Western Africa highlighted the need for anti-EBOV therapeutics. Clomiphene is a U.S. Food and Drug Administration (FDA)-approved drug that blocks EBOV entry and infection in cells and significantly protects EBOV-challenged mice. As provided, clomiphene is, approximately, a 60:40 mixture of two stereoisomers, enclomiphene and zuclomiphene. The pharmacokinetic properties of the two isomers vary, but both accumulate in the eye and male reproductive tract, tissues in which EBOV can persist. Here we compared the ability of clomiphene and its isomers to inhibit EBOV using viral-like particle (VLP) entry and transcription/replication-competent VLP (trVLP) assays. Clomiphene and its isomers inhibited the entry and infection of VLPs and trVLPs with similar potencies. This was demonstrated with VLPs bearing the glycoproteins from three filoviruses (EBOV Mayinga, EBOV Makona, and Marburg virus) and in two cell lines (293T/17 and Vero E6). Visual problems have been noted in EBOV survivors, and viral RNA has been isolated from semen up to nine months post-infection. Since the clomiphene isomers accumulate in these affected tissues, clomiphene or one of its isomers warrants consideration as an anti-EBOV agent, for example, to potentially help ameliorate symptoms in EBOV survivors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4997570/ doi: 10.3390/v8080206 id: cord-355737-o0y4rn0z author: Ng, Melinda title: Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats date: 2015-12-23 words: 8935 sentences: 422 pages: flesch: 49 cache: ./cache/cord-355737-o0y4rn0z.txt txt: ./txt/cord-355737-o0y4rn0z.txt summary: To assess whether the EBOV infection defect in the African straw-colored fruit bat cells occurs at the viral entry step, we exposed an expanded panel of kidney fibroblast cell lines from four African pteropodids to VSV pseudotypes bearing GP spikes (VSV-GP) from seven filoviruses, including two non-African viruses, Reston virus (RESTV) and Lloviu virus (LLOV) ( Figure 1D ). Like the infection defect in African straw-colored fruit bat cells, this receptor binding defect was selective for EBOV GP, since GPs derived from MARV and the European filovirus, LLOV (Ng et al., 2014) , bound equivalently to all four pteropodid domain Cs ( Figure 4A ). . We conclude that a species-specific defect in virus-receptor interaction, caused by a single amino acid residue change in EhNPC1 relative to other, permissive African pteropodid NPC1 orthologs, reduces EBOV infection in African straw-colored fruit bat cells. abstract: Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. DOI: http://dx.doi.org/10.7554/eLife.11785.001 url: https://doi.org/10.7554/elife.11785 doi: 10.7554/elife.11785 id: cord-350083-kldu8q8x author: Oany, Arafat Rahman title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach date: 2015-08-08 words: 5019 sentences: 315 pages: flesch: 51 cache: ./cache/cord-350083-kldu8q8x.txt txt: ./txt/cord-350083-kldu8q8x.txt summary: title: Highly conserved regions in Ebola virus RNA dependent RNA polymerase may be act as a universal novel peptide vaccine target: a computational approach METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. To date, information regarding the processing, structure and functions of Ebola virus (EBOV) protein L (EBOL) demonstrates that it is an RNA-dependent RNA polymerase, with the assistance of VP35. In the present study, we have followed immunoinformatics approaches for designing potential conserved epitope candidate for the utility of vaccine development against the deadly Ebola virus, with an expectation of further wet lab validation. Protein variability server predicted the variability of the conserved region of the RNA-dependent RNA polymerase-L ( Fig. 10) to ensure that the proposed epitope is within the invariable region. Design of an epitope-based peptide vaccine against spike protein of human corona virus: an in silico approach abstract: PURPOSE: Ebola virus (EBOV) is such kind of virus which is responsible for 23,825 cases and 9675 deaths worldwide only in 2014 and with an average diseases fatality rate between 25 % and 90 %. Although, medical technology has tried to handle the problems, there is no Food and Drug Administration (FDA)-approved therapeutics or vaccines available for the prevention, post exposure, or treatment of Ebola virus disease (EVD). METHODS: In the present study, we used the immunoinformatics approach to design a potential epitope-based vaccine against the RNA-dependent RNA polymerase-L of EBOV. BioEdit v7.2.3 sequence alignment editor, Jalview v2 and CLC Sequence Viewer v7.0.2 were used for the initial sequence analysis for securing the conservancy from the sequences. Later the Immune Epitope Database and Analysis Resource (IEDB-AR) was used for the identification of T-cell and B-cellepitopes associated with type I and II major histocompatibility complex molecules analysis. Finally, the population coverage analysis was employed. RESULTS: The core epitope “FRYEFTAPF” was found to be the most potential one, with 100 % conservancy among all the strains of EBOV. It also interacted with both type I and II major histocompatibility complex molecules and is considered as nonallergenic in nature. Finally, with impressive cumulative population coverage of 99.87 % for the both MHC-I and MHC-II class throughout the world population was found for the proposed epitope. CONCLUSION: To end, the projected peptide gave us a solid stand to propose for vaccine consideration and that might be experimented for its potency in eliciting immunity through humoral and cell mediated immune responses in vitro and in vivo. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s40203-015-0011-4) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1186/s40203-015-0011-4 doi: 10.1186/s40203-015-0011-4 id: cord-267941-nrluar4e author: Park, Eun-Mee title: Production of Ebola virus-like particles in Drosophila melanogaster Schneider 2 cells date: 2018-08-23 words: 2162 sentences: 127 pages: flesch: 55 cache: ./cache/cord-267941-nrluar4e.txt txt: ./txt/cord-267941-nrluar4e.txt summary: In this study, we generated recombinant virus-like particles (VLPs) against family Filoviridae, genus Ebolavirus, species Zaire ebolavirus, strain Makona (EBOV) in Drosophila melanogaster Schneider 2 (S2) cells using the EBOV Makona. eVLPs were produced by sucrose gradient ultracentrifugation of S2 cells transfected with EBOV Makona genes, and production of VLPs was confirmed by immunoblot analysis. In a previous study, VP2/6 double-layered rotavirus-like particles containing Wa capsid protein were produced in S2 cells transformed with a bicistronic expression system consisting of encephalomyocarditis virus (EMCV)-derived internal ribosomal entry site (IRES) element (Lee et al., 2011) . As shown in Fig. 1A , we confirmed that Ebola viral proteins were efficiently expressed in EBOV Makona-transfected S2 cells. Collectively, our findings suggested that the eVLPs produced by the S2 cell system in this study may be useful for the development of efficient VLP-based vaccines against EBOV. abstract: In this study, we generated recombinant virus-like particles (VLPs) against family Filoviridae, genus Ebolavirus, species Zaire ebolavirus, strain Makona (EBOV) in Drosophila melanogaster Schneider 2 (S2) cells using the EBOV Makona. S2 cells were cotransfected with four viral plasmids encoding EBOV Makona proteins and protein expression was analyzed by immunoblotting. We confirmed that EBOV Makona proteins were successfully expressed in S2 cells. Additionally, we further examined the formation of intracellular and extracellular VLPs by electron microscopy. eVLPs were produced by sucrose gradient ultracentrifugation of S2 cells transfected with EBOV Makona genes, and production of VLPs was confirmed by immunoblot analysis. Collectively, our findings showed that the S2 cell system could be a promising tool for efficient production of eVLPs. url: https://api.elsevier.com/content/article/pii/S0166093418304208 doi: 10.1016/j.jviromet.2018.08.016 id: cord-003859-k8wfyj9b author: Paweska, Janusz T. title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera date: 2019-07-24 words: 6407 sentences: 308 pages: flesch: 51 cache: ./cache/cord-003859-k8wfyj9b.txt txt: ./txt/cord-003859-k8wfyj9b.txt summary: title: Evaluation of Diagnostic Performance of Three Indirect Enzyme-Linked Immunosorbent Assays for the Detection of IgG Antibodies to Ebola Virus in Human Sera Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). The purpose of this study was to evaluate and compare the diagnostic performance of EBOV IgG-indirect ELISAs based on antigens produced by classical virological and recombinant protein expression methods using human serum panels from EBOV non-infected and EBOV infected humans. abstract: Filovirus serological diagnosis and epidemiological investigations are hampered due to the unavailability of validated immunoassays. Diagnostic performance of three indirect enzyme-linked immunosorbent assays (I-ELISA) was evaluated for the detection of IgG antibody to Ebola virus (EBOV) in human sera. One I-ELISA was based on a whole EBOV antigen (WAg) and two utilized recombinant nucleocapsid (NP) and glycoproteins (GP), respectively. Validation data sets derived from individual sera collected in South Africa (SA), representing an EBOV non-endemic country, and from sera collected during an Ebola disease (EBOD) outbreak in Sierra Leone (SL), were categorized according to the compounded results of the three I-ELISAs and real time reverse-transcription polymerase chain reaction (RT-PCR). At the cut-off values selected at 95% accuracy level by the two-graph receiver operating characteristic analysis, specificity in the SA EBOV negative serum panel (n = 273) ranged from 98.17% (GP ELISA) to 99.27% (WAg ELISA). Diagnostic specificity in the SL EBOV negative panel (n = 676) was 100% by the three ELISAs. The diagnostic sensitivity in 423 RT-PCR confirmed EBOD patients was dependent on the time when the serum was collected after onset of disease. It significantly increased 2 weeks post-onset, reaching 100% sensitivity by WAg and NP and 98.1% by GP I-ELISA. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6722596/ doi: 10.3390/v11080678 id: cord-004335-bw3tziup author: Perez-Zsolt, Daniel title: When Dendritic Cells Go Viral: The Role of Siglec-1 in Host Defense and Dissemination of Enveloped Viruses date: 2019-12-19 words: 7360 sentences: 388 pages: flesch: 40 cache: ./cache/cord-004335-bw3tziup.txt txt: ./txt/cord-004335-bw3tziup.txt summary: Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. Thus, infection with viruses such as HIV-1 or EBOV tightly upregulates Siglec-1 expression on APCs, as they directly trigger or indirectly promote the release of type I IFNs via immune activating factors (Figure 1 ). Thus, HIV-1 and EBOV infections trigger an immune activation state that upregulates Siglec-1 expression on DCs, a situation that might favor early viral dissemination events in an otherwise antiviral environment [80] . abstract: Dendritic cells (DCs) are among the first cells that recognize incoming viruses at the mucosal portals of entry. Initial interaction between DCs and viruses facilitates cell activation and migration to secondary lymphoid tissues, where these antigen presenting cells (APCs) prime specific adaptive immune responses. Some viruses, however, have evolved strategies to subvert the migratory capacity of DCs as a way to disseminate infection systemically. Here we focus on the role of Siglec-1, a sialic acid-binding type I lectin receptor potently upregulated by type I interferons on DCs, that acts as a double edge sword, containing viral replication through the induction of antiviral immunity, but also favoring viral spread within tissues. Such is the case for distant enveloped viruses like human immunodeficiency virus (HIV)-1 or Ebola virus (EBOV), which incorporate sialic acid-containing gangliosides on their viral membrane and are effectively recognized by Siglec-1. Here we review how Siglec-1 is highly induced on the surface of human DCs upon viral infection, the way this impacts different antigen presentation pathways, and how enveloped viruses have evolved to exploit these APC functions as a potent dissemination strategy in different anatomical compartments. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019426/ doi: 10.3390/v12010008 id: cord-002935-jq1xumrh author: Postnikova, Elena title: Testing therapeutics in cell-based assays: Factors that influence the apparent potency of drugs date: 2018-03-22 words: 6226 sentences: 315 pages: flesch: 56 cache: ./cache/cord-002935-jq1xumrh.txt txt: ./txt/cord-002935-jq1xumrh.txt summary: Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate. The CELIA was compared to the fluorescent assay (detected by regular plate reader or the HCI system) by testing the efficacy of toremifene citrate against EBOV infection in Huh 7 cells with a range of MOIs (0.1, 0.3, 1, and 3 ) at three different time points (24, 48 and 72 hpi) . The established CELIA was used to compare anti-EBOV activity of toremifene citrate in 3 different cell types, Vero E6, Huh 7 and MDMs using an MOI of 0.5 and a time point of 48 h (Fig 7) . abstract: Identifying effective antivirals for treating Ebola virus disease (EVD) and minimizing transmission of such disease is critical. A variety of cell-based assays have been developed for evaluating compounds for activity against Ebola virus. However, very few reports discuss the variable assay conditions that can affect the results obtained from these drug screens. Here, we describe variable conditions tested during the development of our cell-based drug screen assays designed to identify compounds with anti-Ebola virus activity using established cell lines and human primary cells. The effect of multiple assay readouts and variable assay conditions, including virus input, time of infection, and the cell passage number, were compared, and the impact on the effective concentration for 50% and/ or 90% inhibition (EC(50), EC(90)) was evaluated using the FDA-approved compound, toremifene citrate. In these studies, we show that altering cell-based assay conditions can have an impact on apparent drug potency as measured by the EC(50). These results further support the importance of developing standard operating procedures for generating reliable and reproducible in vitro data sets for potential antivirals. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5864066/ doi: 10.1371/journal.pone.0194880 id: cord-303647-c4umbcvn author: Reed, Patricia E. title: A New Approach for Monitoring Ebolavirus in Wild Great Apes date: 2014-09-18 words: 5636 sentences: 256 pages: flesch: 46 cache: ./cache/cord-303647-c4umbcvn.txt txt: ./txt/cord-303647-c4umbcvn.txt summary: CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. In zone A, 20 gorilla fecal samples were opportunistically collected while following habituated gorillas roughly 2 and 3 years after ebolavirus infection was confirmed in ape carcasses at that site using a combination of RT-PCR, immunohistochemistry and antigen capture [5, 9] . All human EVD outbreaks that had previously occurred in our sampling zone study are thought to be the result of handling infected wild animal carcasses, including gorillas [13] . This study represents the first time that ebolavirus antibodies have been detected in wild great ape fecal samples, and carries important implications for the future management and survival of these primates. abstract: BACKGROUND: Central Africa is a “hotspot” for emerging infectious diseases (EIDs) of global and local importance, and a current outbreak of ebolavirus is affecting multiple countries simultaneously. Ebolavirus is suspected to have caused recent declines in resident great apes. While ebolavirus vaccines have been proposed as an intervention to protect apes, their effectiveness would be improved if we could diagnostically confirm Ebola virus disease (EVD) as the cause of die-offs, establish ebolavirus geographical distribution, identify immunologically naïve populations, and determine whether apes survive virus exposure. METHODOLOGY/PRINCIPAL FINDINGS: Here we report the first successful noninvasive detection of antibodies against Ebola virus (EBOV) from wild ape feces. Using this method, we have been able to identify gorillas with antibodies to EBOV with an overall prevalence rate reaching 10% on average, demonstrating that EBOV exposure or infection is not uniformly lethal in this species. Furthermore, evidence of antibodies was identified in gorillas thought previously to be unexposed to EBOV (protected from exposure by rivers as topological barriers of transmission). CONCLUSIONS/SIGNIFICANCE: Our new approach will contribute to a strategy to protect apes from future EBOV infections by early detection of increased incidence of exposure, by identifying immunologically naïve at-risk populations as potential targets for vaccination, and by providing a means to track vaccine efficacy if such intervention is deemed appropriate. Finally, since human EVD is linked to contact with infected wildlife carcasses, efforts aimed at identifying great ape outbreaks could have a profound impact on public health in local communities, where EBOV causes case-fatality rates of up to 88%. url: https://www.ncbi.nlm.nih.gov/pubmed/25232832/ doi: 10.1371/journal.pntd.0003143 id: cord-305653-f9vqn96o author: Schmidt, Rebecca title: Generation of therapeutic antisera for emerging viral infections date: 2018-10-05 words: 7902 sentences: 377 pages: flesch: 46 cache: ./cache/cord-305653-f9vqn96o.txt txt: ./txt/cord-305653-f9vqn96o.txt summary: Animal-origin purified IgG 27 and IgG fragment preparations are still routinely used as antivenoms, and even though immunization of horses with inactivated EBOV failed to yield effective therapeutic antisera, 28 equine hyperimmune sera produced using EBOV virus-like particles (VLPs) conferred protection against lethal challenge in rodents. To determine the importance of this aspect for the induction of functional antibodies, we compared adjuvanted EBOV VLPs with vector vaccines based on the replication-deficient modified vaccinia Ankara virus (MVA) that expresses either the GP protein of the Zaire EBOV Guéckédou strain alone or in combination with VP40 (unpublished data), and the replication-competent VSVΔG/EBOV-GP. Even though the neutralizing antibodies were again only detected after the first boost in the group immunized with adjuvanted EBOV VLPs, titers ultimately reached levels around 100 (Fig. 2b) , illustrating that de novo protein expression is not required for efficient induction of functional antibodies. abstract: The recent Ebola virus outbreak has highlighted the therapeutic potential of antisera and renewed interest in this treatment approach. While human convalescent sera may not be readily available in the early stages of an outbreak, antisera of animal origin can be produced in a short time frame. Here, we compared adjuvanted virus-like particles (VLP) with recombinant modified vaccinia virus Ankara and vesicular stomatitis virus (VSV), both expressing the Ebola virus antigens. The neutralizing antibody titers of rabbits immunized with adjuvanted VLPs were similar to those immunized with the replication-competent VSV, indicating that presentation of the antigen in its native conformation rather than de novo antigen expression is essential for production of functional antibodies. This approach also yielded high-titer antisera against Nipah virus glycoproteins, illustrating that it is transferable to other virus families. Multiple-step immunoglobulin G purification using a two-step 20–40% ammonium sulfate precipitation followed by protein A affinity chromatography resulted in 90% recovery of functionality and sustained in vivo stability. Adjuvanted VLP-based immunization strategies are thus a promising approach for the rapid generation of therapeutic antisera against emerging infections. url: https://doi.org/10.1038/s41541-018-0082-4 doi: 10.1038/s41541-018-0082-4 id: cord-102206-mb0qcd0b author: Seymour, Elif title: Configurable Digital Virus Counter on Robust Universal DNA Chips date: 2020-10-22 words: 5898 sentences: 284 pages: flesch: 52 cache: ./cache/cord-102206-mb0qcd0b.txt txt: ./txt/cord-102206-mb0qcd0b.txt summary: 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). 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. 16 SP-IRIS has been utilized for detecting viruses in complex media using antibody microarrays by imaging chips both dry (dried after sample incubation and wash steps) and in liquid using disposable microfluidic cartridges. To demonstrate the feasibility of using the homogeneous assay in combination with the passive flow cartridge and to compare its performance to the directly immobilized antibody assay, an SP-IRIS chip was printed with anti-EBOV mAb, A'' probe, and a negative DNA sequence, and washed as described previously. 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-003779-5yhoiv76 author: Singleton, Courtney D. title: Identification of Ebola Virus Inhibitors Targeting GP2 Using Principles of Molecular Mimicry date: 2019-07-17 words: 8976 sentences: 434 pages: flesch: 48 cache: ./cache/cord-003779-5yhoiv76.txt txt: ./txt/cord-003779-5yhoiv76.txt summary: Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV. The computational screening resulted in the prioritization and purchase of 165 compounds for experimental characterization, which led to 11 hits that inhibit viral entry in both EBOV-GP-pseudotyped virus and EBOV transcription-and replicationcompetent virus-like particle (trVLP) systems. Molecular dynamics (MD) simulations in conjunction with genome analysis identified 7 highly conserved residues across different Ebola virus strains (E564.A, A568.A, L571.A, F572.A, T566.C, L569.C, and L573.C) that contribute a majority of the favorable interactions between the compounds and GP2. abstract: A key step in the Ebola virus (EBOV) replication cycle involves conformational changes in viral glycoprotein 2 (GP2) which facilitate host-viral membrane fusion and subsequent release of the viral genome. Ebola GP2 plays a critical role in virus entry and has similarities in mechanism and structure to the HIV gp41 protein for which inhibitors have been successfully developed. In this work, a putative binding pocket for the C-terminal heptad repeat in the N-terminal heptad repeat trimer was targeted for identification of small molecules that arrest EBOV-host membrane fusion. Two computational structure-based virtual screens of ∼1.7 M compounds were performed (DOCK program) against a GP2 five-helix bundle, resulting in 165 commercially available compounds purchased for experimental testing. Based on assessment of inhibitory activity, cytotoxicity, and target specificity, four promising candidates emerged with 50% inhibitory concentration values in the 3 to 26 μM range. Molecular dynamics simulations of the two most potent candidates in their DOCK-predicted binding poses indicate that the majority of favorable interactions involve seven highly conserved residues that can be used to guide further inhibitor development and refinement targeting EBOV. IMPORTANCE The most recent Ebola virus disease outbreak, from 2014 to 2016, resulted in approximately 28,000 individuals becoming infected, which led to over 12,000 causalities worldwide. The particularly high pathogenicity of the virus makes paramount the identification and development of promising lead compounds to serve as inhibitors of Ebola infection. To limit viral load, the virus-host membrane fusion event can be targeted through the inhibition of the class I fusion glycoprotein of Ebolavirus. In the current work, several promising small-molecule inhibitors that target the glycoprotein GP2 were identified through systematic application of structure-based computational and experimental drug design procedures. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6639268/ doi: 10.1128/jvi.00676-19 id: cord-318587-ewvnkdr2 author: Steeds, Kimberley title: Pseudotyping of VSV with Ebola virus glycoprotein is superior to HIV-1 for the assessment of neutralising antibodies date: 2020-08-31 words: 4973 sentences: 244 pages: flesch: 46 cache: ./cache/cord-318587-ewvnkdr2.txt txt: ./txt/cord-318587-ewvnkdr2.txt summary: We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The aim of this study was to assess the suitability of EBOV GP pseudotyped HIV-1 and VSV systems to measure neutralisation by EVD survivor plasma, in comparison with results from a live EBOV neutralisation assay. To determine the optimal pseudotyped virus input to use in the HIV-and VSV-based assays, neutralisation of different amounts of the EBOV GP pseudotyped viruses by plasma from a Guinean EVD survivor donor or human anti-EBOV GP mAb KZ52 was assessed. When IC 50 values of EBOV GP pseudotyped HIV-1 neutralisation of the 30 EVD survivor and 10 negative plasma samples were compared with GMT values for the live EBOV neutralisation assay, a positive correlation (r s = 0.54) was determined using the nonparametric Spearman correlation coefficient (Fig. 5a) and this was statistically significant (p = 0.0004). abstract: Ebola virus (EBOV) is an enveloped, single-stranded RNA virus that can cause Ebola virus disease (EVD). It is thought that EVD survivors are protected against subsequent infection with EBOV and that neutralising antibodies to the viral surface glycoprotein (GP) are potential correlates of protection. Serological studies are vital to assess neutralising antibodies targeted to EBOV GP; however, handling of EBOV is limited to containment level 4 laboratories. Pseudotyped viruses can be used as alternatives to live viruses, which require high levels of bio-containment, in serological and viral entry assays. However, neutralisation capacity can differ among pseudotyped virus platforms. We evaluated the suitability of EBOV GP pseudotyped human immunodeficiency virus type 1 (HIV-1) and vesicular stomatitis virus (VSV) to measure the neutralising ability of plasma from EVD survivors, when compared to results from a live EBOV neutralisation assay. The sensitivity, specificity and correlation with live EBOV neutralisation were greater for the VSV-based pseudotyped virus system, which is particularly important when evaluating EBOV vaccine responses and immuno-therapeutics. Therefore, the EBOV GP pseudotyped VSV neutralisation assay reported here could be used to provide a better understanding of the putative correlates of protection against EBOV. url: https://www.ncbi.nlm.nih.gov/pubmed/32868837/ doi: 10.1038/s41598-020-71225-1 id: cord-337998-08tknscm author: Sztuba-Solinska, Joanna title: A small stem-loop structure of the Ebola virus trailer is essential for replication and interacts with heat-shock protein A8 date: 2016-11-16 words: 8269 sentences: 434 pages: flesch: 51 cache: ./cache/cord-337998-08tknscm.txt txt: ./txt/cord-337998-08tknscm.txt summary: Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. 3E-5E-GFP minigenome RNA secondary structure and host protein interactions were examined using selective 2 -hydroxyl acylation analyzed by primer extension (SHAPE) (38, 39) , antisense-interfered SHAPE (aiSHAPE) (40) , electrophoretic mobility shift assays (EMSA), siRNA, and mutational analysis, using both the 3E-5E-GFP minigenome system and EBOV reverse genetics. The secondary structure of the EBOV 3E-5E-GFP minigenome RNA predicted by RNAstructure software version 5.7 (48) and chemical probing data from SHAPE were used to generate 10 three-dimensional (3D) models for the trailer-to-leader panhandle interaction in the wt-EBOV genome and variants, A30U and A26U/A30U, using open-source RNAComposer, version 1.0 (http://rnacomposer.cs.put.poznan.pl/). abstract: Ebola virus (EBOV) is a single-stranded negative-sense RNA virus belonging to the Filoviridae family. The leader and trailer non-coding regions of the EBOV genome likely regulate its transcription, replication, and progeny genome packaging. We investigated the cis-acting RNA signals involved in RNA–RNA and RNA–protein interactions that regulate replication of eGFP-encoding EBOV minigenomic RNA and identified heat shock cognate protein family A (HSC70) member 8 (HSPA8) as an EBOV trailer-interacting host protein. Mutational analysis of the trailer HSPA8 binding motif revealed that this interaction is essential for EBOV minigenome replication. Selective 2′-hydroxyl acylation analyzed by primer extension analysis of the secondary structure of the EBOV minigenomic RNA indicates formation of a small stem-loop composed of the HSPA8 motif, a 3′ stem-loop (nucleotides 1868–1890) that is similar to a previously identified structure in the replicative intermediate (RI) RNA and a panhandle domain involving a trailer-to-leader interaction. Results of minigenome assays and an EBOV reverse genetic system rescue support a role for both the panhandle domain and HSPA8 motif 1 in virus replication. url: https://www.ncbi.nlm.nih.gov/pubmed/27651462/ doi: 10.1093/nar/gkw825 id: cord-017811-w38mbvdw author: Volchkov, Viktor title: Proteolytic Processing of Filovirus Glycoproteins date: 2018-02-16 words: 3525 sentences: 186 pages: flesch: 53 cache: ./cache/cord-017811-w38mbvdw.txt txt: ./txt/cord-017811-w38mbvdw.txt summary: After entering cells by macropinocytosis, the glycan cap and the mucin-like domain are removed from GP1 by endosomal cathepsins B and L exposing the binding site for the Niemann-Pick C1 receptor. The surface glycoprotein of MARV is proteolytically processed in a similar way as that of EBOV; two precursor molecules and mature GP1,2 consisting of the disulfide-linked cleavage products GP1 and GP2 were identified in cells expressing MARV GP and in Marburg virions (Volchkov et al. Like EBOV, MARV enters cells by macropinocytosis and endosomal fusion, but there are some differences in the structure and in endosomal processing of the glycoproteins. Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression Endoproteolytic processing of the Ebola virus envelope glycoprotein: cleavage is not required for function abstract: Filoviruses (Marburg virus and Ebola virus) have a single envelope glycoprotein (GP) that initiates infection. GP is a class I fusion protein that forms trimeric spikes composed of heterodimers of the subunits GP1 and GP2. GP1 and GP2 are derived from the precursor pre-GP by furin cleavage during exocytosis. GP1 contains a receptor-binding core topped by a glycan cap and a heavily glycosylated mucin-like domain, while GP2 contains a fusion loop and a membrane anchor. After entering cells by macropinocytosis, the glycan cap and the mucin-like domain are removed from GP1 by endosomal cathepsins B and L exposing the binding site for the Niemann-Pick C1 receptor. It appears that there is no strict requirement for specific proteases involved in GP processing. Thus, furin is not indispensible for GP1-2 cleavage, and GP1 may be trimmed not only by cathepsins B and L but also by other endosomal proteases. Two soluble glycoproteins of Ebola virus are also processed by host proteases. A significant amount of GP1,2 is cleaved by the metalloprotease TACE and shed from the surface of infected cells (GP1,2 delta). The secreted protein sGP is derived from the precursor pre-sGP by furin cleavage. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122482/ doi: 10.1007/978-3-319-75474-1_5 id: cord-272576-ez731lif author: Wada, Yoshiko title: Directional and reoccurring sequence change in zoonotic RNA virus genomes visualized by time-series word count date: 2016-11-03 words: 5641 sentences: 273 pages: flesch: 50 cache: ./cache/cord-272576-ez731lif.txt txt: ./txt/cord-272576-ez731lif.txt summary: To face the world-wide threats caused by zoonotic RNA viruses, which suddenly cause serious outbreaks by invasion from nonhuman hosts and mutate rapidly, we must understand the molecular evolutionary changes in their genome sequences extensively by innovating various technologies, including those used in big data analyses, e.g., large-scale word count. The present time-series analysis on influenza A genomes showed that the 20-mers exhibiting the most evident directional changes observed in common for three different subtypes corresponded to several influenza A siRNAs, which were experimentally validated. The present study focused on time-series changes, but not on data variations caused largely by random mutations and sequencing uncertainty, and therefore, average characteristics of strains isolated in a similar period were analyzed, summing up the sequences isolated in one month and calculating an averaged mononucleotide composition for each month (Fig. 1b) . abstract: Ebolavirus, MERS coronavirus and influenza virus are zoonotic RNA viruses, which mutate very rapidly. Viral growth depends on many host factors, but human cells may not provide the ideal growth conditions for viruses invading from nonhuman hosts. The present time-series analyses of short and long oligonucleotide compositions in these genomes showed directional changes in their composition after invasion from a nonhuman host, which are thought to recur after future invasions. In the recent West Africa Ebola outbreak, directional time-series changes in a wide range of oligonucleotides were observed in common for three geographic areas, and the directional changes were observed also for the recent MERS coronavirus epidemics starting in the Middle East. In addition, common directional changes in human influenza A viruses were observed for three subtypes, whose epidemics started independently. Long oligonucleotides that showed an evident directional change observed in common for the three subtypes corresponded to some of influenza A siRNAs, whose activities have been experimentally proven. Predicting directional and reoccurring changes in oligonucleotide composition should become important for designing diagnostic RT-PCR primers and therapeutic oligonucleotides with long effectiveness. url: https://www.ncbi.nlm.nih.gov/pubmed/27808119/ doi: 10.1038/srep36197 id: cord-346267-l08ld2cy author: Wertheim, Joel O. title: Purifying Selection Can Obscure the Ancient Age of Viral Lineages date: 2011-06-24 words: 6414 sentences: 327 pages: flesch: 47 cache: ./cache/cord-346267-l08ld2cy.txt txt: ./txt/cord-346267-l08ld2cy.txt summary: Over longer periods of evolutionary time (i.e., along long internal branches on a phylogenetic tree), evidence of evolution at the nucleotide level could be lost, which could bias tMRCA estimates towards younger dates (i.e., underestimate the length of these branches). The results presented here demonstrate that not accounting for purifying selection may bias tMRCA estimation in RNA viruses towards more recent dates, and a degree of correction can be realized by employing more realistic codon-based substitution models, capable of partially accounting for the biasing effect of purifying selection. Using BMCMC analysis, we inferred the substitution rate and root age under a standard nucleotide substitution model (GTR + Γ 4 ) for each of our three viral data sets: MeV/RPV/PPRV nucleoprotein, EBOV glycoprotein, and AIV neuraminidase (table 1) . The nucleotide substitution model (GTR + Γ 4 ) underestimated the length of branches simulated under empirical (IFEL) selection regimes inferred from the three viral data sets ( fig. abstract: Statistical methods for molecular dating of viral origins have been used extensively to infer the time of most common recent ancestor for many rapidly evolving pathogens. However, there are a number of cases, in which epidemiological, historical, or genomic evidence suggests much older viral origins than those obtained via molecular dating. We demonstrate how pervasive purifying selection can mask the ancient origins of recently sampled pathogens, in part due to the inability of nucleotide-based substitution models to properly account for complex patterns of spatial and temporal variability in selective pressures. We use codon-based substitution models to infer the length of branches in viral phylogenies; these models produce estimates that are often considerably longer than those obtained with traditional nucleotide-based substitution models. Correcting the apparent underestimation of branch lengths suggests substantially older origins for measles, Ebola, and avian influenza viruses. This work helps to reconcile some of the inconsistencies between molecular dating and other types of evidence concerning the age of viral lineages. url: https://www.ncbi.nlm.nih.gov/pubmed/21705379/ doi: 10.1093/molbev/msr170 id: cord-284791-bgodmbru author: Whitworth, Carrie title: Persistence of Bacteriophage Phi 6 on Porous and Nonporous Surfaces and the Potential for Its Use as an Ebola Virus or Coronavirus Surrogate date: 2020-08-18 words: 5152 sentences: 250 pages: flesch: 55 cache: ./cache/cord-284791-bgodmbru.txt txt: ./txt/cord-284791-bgodmbru.txt summary: The persistence of phi 6 was evaluated as a surrogate for Ebola virus (EBOV) and coronaviruses on porous and nonporous hospital surfaces. Under these laboratory-simulated Western indoor hospital conditions, we assessed the suitability of phi 6 as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses. This study evaluated the persistence of phi 6 in the presence of artificial test soil (ATS) as a potential surrogate for EBOV or coronaviruses at two absolute humidity (AH) conditions on four potential fomites: nonporous stainless steel (SS) and plastic (PL) and two types of porous hospital curtain fabrics. found that the Phi 6 was shown here in the current study to be a conservative surrogate for EBOV in a laboratory-simulated Western hospital room condition of 3.0 g/m 3 AH, persisting longer than the Makona-C05 variant (AH ϭ 3.3 g/m 3 ), with decay rates of 0.06 log 10 /d and 0.79 log 10 /h, respectively (Table 1 ). abstract: The infection of health care workers during the 2013 to 2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the coronavirus disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of phi 6 was evaluated as a surrogate for Ebola virus (EBOV) and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1-cm(2) coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels: a low AH of 3.0 g/m(3) and a high AH of 14.4 g/m(3). Phi 6 declined at a lower rate on all materials under low-AH conditions, with a decay rate of 0.06-log(10) PFU/day to 0.11-log(10) PFU/day, than under the higher AH conditions, with a decay rate of 0.65-log(10) PFU/h to 1.42-log(10) PFU/day. There was a significant difference in decay rates between porous and nonporous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, phi 6 was found to be a conservative surrogate for EBOV under low-AH conditions in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi 6 under similar conditions; therefore, phi 6 may not be a suitable surrogate for coronaviruses. IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in health care facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated Western indoor hospital conditions, we assessed the suitability of phi 6 as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses. url: https://www.ncbi.nlm.nih.gov/pubmed/32591388/ doi: 10.1128/aem.01482-20 id: cord-296517-414grqif author: Wong, Gary title: MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease date: 2015-10-14 words: 2880 sentences: 129 pages: flesch: 50 cache: ./cache/cord-296517-414grqif.txt txt: ./txt/cord-296517-414grqif.txt summary: In September 2012, Middle East Respiratory Syndrome coronavirus (MERS-CoV) emerged as a novel virus that can result in severe respiratory disease with renal failure, with a case fatality rate of up to 38%. Notably, between May and July 2015, an outbreak of MERS-CoV centered in South Korea killed 36 people out of 186 confirmed cases (Promedmail.org, 2015) , with thousands quarantined as health authorities attempted to control virus spread. The 2015 MERS-CoV outbreak in South Korea began from an imported case, a 68-year-old male with a recent travel history to several Middle Eastern countries, including Bahrain, the United Arab Emirates, Saudi Arabia, and Qatar. Thus, the MERS-CoV outbreak in South Korea was driven primarily by three infected individuals, and approximately 75% of cases can be traced back to three super-spreaders who have each infected a disproportionately high number of contacts ( Figure 1A ). abstract: Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014–15 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading. url: https://doi.org/10.1016/j.chom.2015.09.013 doi: 10.1016/j.chom.2015.09.013 id: cord-330647-w1bpeqzg author: Wong, Samson Sai-Yin title: Ebola virus disease in nonendemic countries date: 2015-05-31 words: 8637 sentences: 507 pages: flesch: 41 cache: ./cache/cord-330647-w1bpeqzg.txt txt: ./txt/cord-330647-w1bpeqzg.txt summary: The largest outbreak of Ebola virus disease (EVD) in history has renewed interest in filoviruses and has provided an unprecedented impetus to the development of new therapeutics and vaccines for this highly lethal infection. Nucleic acid amplification is the diagnostic test of choice because of its high sensitivity (especially in the early phase of illness); its ability to differentiate between different agents of viral hemorrhagic fever; and its relatively lower biohazard, if the viruses are appropriately inactivated; and because antigen and antibody assays are often unavailable in laboratories in nonendemic countries. 119e123 Animal studies also demonstrate the efficacy of favipiravir in the treatment of Junín virus, arenavirus, and EBOV hemorrhagic fevers, and the drug was used to treat human EVD in the 2014 West African epidemic. abstract: The 2014 West African outbreak of Ebola virus disease was unprecedented in its scale and has resulted in transmissions outside endemic countries. Clinicians in nonendemic countries will most likely face the disease in returning travelers, either among healthcare workers, expatriates, or visiting friends and relatives. Clinical suspicion for the disease must be heightened for travelers or contacts presenting with compatible clinical syndromes, and strict infection control measures must be promptly implemented to minimize the risk of secondary transmission within healthcare settings or in the community. We present a concise review on human filoviral disease with an emphasis on issues that are pertinent to clinicians practicing in nonendemic countries. url: https://api.elsevier.com/content/article/pii/S0929664615000637 doi: 10.1016/j.jfma.2015.01.012 id: cord-322748-a5131tv9 author: Yates, Mary K. title: Flex-nucleoside analogues – Novel therapeutics against filoviruses date: 2017-06-15 words: 1492 sentences: 78 pages: flesch: 53 cache: ./cache/cord-322748-a5131tv9.txt txt: ./txt/cord-322748-a5131tv9.txt summary: Most recently GS-5734, a monophosphoramidate prodrug adenosine analogue which targets EBOV RNA-dependent RNA polymerase (RdRp), exhibited very potent activity against both EBOV and MARV, 17, 18 further demonstrating the potential for finding effective nucleoside inhibitors of filoviruses. After the successful synthesis of the three Flex-analogues 1, 2, and 3, the compounds were screened against a panel of filoviruses including EBOV, MARV, and SUDV, as well as other hemorrhagic fever viruses such as Lassa and Rift Valley Fever. The second series of assays utilized Huh7 cells infected with recombinant reporter EBOV, Lassa, and Rift Valley Fever viruses. Within this study we found that both compounds 1 and 3 exhibited antiviral activity against a recombinant reporter EBOV in Huh7 cells, though surprisingly the McGuigan prodrug was 10-fold less potent (EC 50 = 2.2 ± 0.3 lM and 27.2 ± 2.2 lM respectively). abstract: Abstract Fleximers, a novel type of flexible nucleoside that have garnered attention due to their unprecedented activity against human coronaviruses, have now exhibited highly promising levels of activity against filoviruses. The Flex-nucleoside was the most potent against recombinant Ebola virus in Huh7 cells with an EC50 =2μM, while the McGuigan prodrug was most active against Sudan virus-infected HeLa cells with an EC50 of 7μM. url: https://www.ncbi.nlm.nih.gov/pubmed/28465098/ doi: 10.1016/j.bmcl.2017.04.069 id: cord-297082-2rhoffx2 author: Yu, Changqing title: MARCH8 Inhibits Ebola Virus Glycoprotein, Human Immunodeficiency Virus Type 1 Envelope Glycoprotein, and Avian Influenza Virus H5N1 Hemagglutinin Maturation date: 2020-09-15 words: 6423 sentences: 410 pages: flesch: 61 cache: ./cache/cord-297082-2rhoffx2.txt txt: ./txt/cord-297082-2rhoffx2.txt summary: Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. As a control, serine incorporator 5 (SERINC5) protein In addition, FLAG-tagged furin was expressed with HA-tagged human MARCH8 and GPΔMLD in 293T cells. In addition, when the furin-VN/GP-VC pair was expressed with MARCH8, their colocalization was also detected (Fig. 2C ), confirming that these three molecules form a complex in live cells. MARCH8 proteins from different species strongly increased GP 1 and GP 1 ΔMLD expression in cells but completely blocked their secretions (Fig. 7C, lanes 1 to 8) . abstract: Membrane-associated RING-CH-type 8 (MARCH8) strongly blocks human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env) incorporation into virions by downregulating its cell surface expression, but the mechanism is still unclear. We now report that MARCH8 also blocks the Ebola virus (EBOV) glycoprotein (GP) incorporation via surface downregulation. To understand how these viral fusion proteins are downregulated, we investigated the effects of MARCH8 on EBOV GP maturation and externalization via the conventional secretion pathway. MARCH8 interacted with EBOV GP and furin when detected by immunoprecipitation and retained the GP/furin complex in the Golgi when their location was tracked by a bimolecular fluorescence complementation (BiFC) assay. MARCH8 did not reduce the GP expression or affect the GP modification by high-mannose N-glycans in the endoplasmic reticulum (ER), but it inhibited the formation of complex N-glycans on the GP in the Golgi. Additionally, the GP O-glycosylation and furin-mediated proteolytic cleavage were also inhibited. Moreover, we identified a novel furin cleavage site on EBOV GP and found that only those fully glycosylated GPs were processed by furin and incorporated into virions. Furthermore, the GP shedding and secretion were all blocked by MARCH8. MARCH8 also blocked the furin-mediated cleavage of HIV-1 Env (gp160) and the highly pathogenic avian influenza virus H5N1 hemagglutinin (HA). We conclude that MARCH8 has a very broad antiviral activity by prohibiting different viral fusion proteins from glycosylation and proteolytic cleavage in the Golgi, which inhibits their transport from the Golgi to the plasma membrane and incorporation into virions. url: https://www.ncbi.nlm.nih.gov/pubmed/32934085/ doi: 10.1128/mbio.01882-20 id: cord-002676-zwkl1ywk author: Yu, Dong-Shan title: The lifecycle of the Ebola virus in host cells date: 2017-06-15 words: 5322 sentences: 287 pages: flesch: 45 cache: ./cache/cord-002676-zwkl1ywk.txt txt: ./txt/cord-002676-zwkl1ywk.txt summary: However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. Then, the Tyro3 protein kinase (TAM) family, including Axl, Dtk, and Mer, which widely expressed in many cell types, span the plasma membrane and contain intracellular tyrosine kinase domains, are facilitate EBOV GP-dependent attachment [39, 40] . In addition, folate receptor-α (FR-α) was reported to be a co-receptor in binding cells that expressed MARV or EBOV GP, mediated syncytia formation triggered by GP, and facilitated cellular entry of the virus [28] . After the virus has been internalized into the endosome, fusion induced by cleaved GP is fundamentally independent of pH, which indicated an unidentified host cell factor critical for filovirus entry is sensitive to an acidic pH [56] . Host Cell Plasma Membrane Phosphatidylserine Regulates the Assembly and Budding of Ebola Virus abstract: Ebola haemorrhagic fever causes deadly disease in humans and non-human primates resulting from infection with the Ebola virus (EBOV) genus of the family Filoviridae. However, the mechanisms of EBOV lifecycle in host cells, including viral entry, membrane fusion, RNP formation, GP-tetherin interaction, and VP40-inner leaflet association remain poorly understood. This review describes the biological functions of EBOV proteins and their roles in the lifecycle, summarizes the factors related to EBOV proteins or RNA expression throughout the different phases, and reviews advances with regards to the molecular events and mechanisms of the EBOV lifecycle. Furthermore, the review outlines the aspects remain unclear that urgently need to be solved in future research. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589696/ doi: 10.18632/oncotarget.18498 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 sentences: 104 pages: flesch: 53 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-002013-rb9xdzro author: Zheng, Xuexing title: Treatment with hyperimmune equine immunoglobulin or immunoglobulin fragments completely protects rodents from Ebola virus infection date: 2016-04-12 words: 6027 sentences: 286 pages: flesch: 56 cache: ./cache/cord-002013-rb9xdzro.txt txt: ./txt/cord-002013-rb9xdzro.txt summary: To investigate whether EBOV infections can be controlled by virus neutralization alone, and to prevent the possible induction of serum sickness in humans that would be administered antisera, the post-exposure efficacy of F(ab′ ) 2 (immunoglobulin treated with pepsin to remove the Fc regions of the antibody) were also investigated side-by-side with equine antisera in all experiments as a potential alternate treatment. Three horses were immunized intramuscularly (IM) with 7 injections of eVLP over 11 weeks and the hyperimmune sera were collected from each animal at specified timepoints ( Fig. 1A) to determine the serum titers by neutralization assay against a recombinant HIV-1 virus pseudotyped with EBOV GP. The observation that administering F(ab′ ) 2 at 1 dpi is more efficacious than when the same treatment was given at 30 minutes post-exposure (Fig. 5A ) was also observed in past studies with therapeutic EBOV GP-specific monoclonal antibodies 25, 26 , and suggests that virus neutralization may play a bigger role in protection at a later timepoint after EBOV challenge. abstract: Recent successes with monoclonal antibody cocktails ZMapp(TM) and MIL77 against Ebola virus (EBOV) infections have reignited interest in antibody-based therapeutics. Since the production process for monoclonal antibodies can be prolonged and costly, alternative treatments should be investigated. We produced purified equine antisera from horses hyperimmunized with EBOV virus-like particles, and tested the post-exposure efficacy of the antisera in a mouse model of infection. BALB/c mice were given up to 2 mg of purified equine antisera per animal, at 30 minutes, 1 or 2 days post-infection (dpi), in which all animals survived. To decrease the possibility of serum sickness, the equine antisera was digested with pepsin to generate F(ab′)(2) fragments, with in vitro neutralizing activity comparable to whole immunoglobulin. Full protection was achieved with when treatment was initiated at 1 dpi, but the suboptimal protection observed with the 30 minute and 2 dpi groups demonstrate that in addition to virus neutralization, other Fc-dependent antibody mechanisms may also contribute to survival. Guinea pigs given 20 mg of antisera or F(ab′)(2) at or starting at 1 or 2 dpi were also fully protected from EBOV infection. These results justify future efficacy studies for purified equine products in NHPs. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4828711/ doi: 10.1038/srep24179 ==== 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